Background Osteoporosis literally means ‘porous bones’. It occurs when the struts which make up the mesh-like structure within bones become thin causing them to become fragile and break easily following a minor bump or fall. Bone growth during childhood and the teenage years is very important as the skeleton grows to achieve full adult height. When osteoporosis occurs it is usually as a result of one of several different medical conditions, or medication. It is also possible that no underlying cause is found and the term idiopathic juvenile (under 16 years of age) osteoporosis is used to describe this. Credits Medical text written December 2012 by Dr M Al Obaidi, Consultant Paediatric Rheumatologist, R Harrison, Research Nurse, Academic Unit of Child Health, Dr P Arundel, Consultant in Metabolic Bone Diseases, Sheffield Children’s NHS Foundation Trust, Sheffield, UK. What are the symptoms? Symptoms will vary from child to child, but may include: pain in the bone often in the back, hips, legs and feetdifficulty in walkingfractures (broken bones) in the long bones of the skeleton and in the spinecurvature of the spine (scoliosis), or a height loss where the bones in the spine have become squashed or misshapen. What are the causes? Primary juvenile osteoporosis is described as bone density loss in a previously healthy child/teenager with a history of bone breaks (arms, legs or spine) for no apparent reason. It is ‘idopathic’ because there is no known cause. Secondary juvenile osteoporosis occurs due to other reasons such as another illness or a medication. Including: inflammatory conditions (such as juvenile arthritis (see entry Arthritis (Juvenile Idiopathic)) or Crohn’s disease (see entry Crohn’s and Ulcerative Colitis))anorexia nervosa (see entry Eating disorders)long-term, high-dose oral corticosteroid treatmentosteogenesis imperfecta (OI) (see entry Brittle Bone disease) – a genetic disorder that affects the collagen, which is an important part of boneconditions causing immobility for example spinal cord injury and cerebral palsy. How is it diagnosed? Juvenile osteoporosis may be discovered when other problems are investigated, such as fractures or difficulty walking. Children will probably be referred to a specialist for further assessment, which can include: X-rays to examine the skeleton for fracturesdual energy x-ray absorptiometry (DXA) – bone density scans to assess the degree of bone density loss. Sometimes other types of scan are used, such as quantitative computerised tomography (QCT or CT)bone biopsies, removal of a small amount of bone tissue, to look at the internal structure of the bone. How is it treated? Parents of children with osteoporosis will be advised to ensure the child has a well-balanced, calcium-rich diet and do plenty of weight-bearing exercise. Physiotherapy may be advised in some children to aid mobility. Some children may need medication that is used in adults with osteoporosis but at smaller doses. Examples include bisphosphonate (drugs that affect the bone cells and the ongoing process of bone renewal) or forms of vitamin D to influence the body’s absorption of calcium. Monitoring will be needed to check the child’s bone density and how the condition is progressing in light of treatment. Inheritance patterns and prenatal diagnosis Inheritance patternsJuvenile osteoporosis has been recognised as more likely to occur in some families, but a genetic cause has not been fully established. Prenatal diagnosisNot applicable. Is there support? Royal Osteoporosis Society Helpline: 0808 800 0035Email: [email protected]Website: theros.org.uk The Society is a Registered Charity in England and Wales No. 11022712. It offers information and support to anyone affected by osteoporosis, including providing information about osteoporosis in children. The Society has a network of support groups across the UK. Group details last updated June 2021.
What are the symptoms? Symptoms will vary from child to child, but may include: pain in the bone often in the back, hips, legs and feetdifficulty in walkingfractures (broken bones) in the long bones of the skeleton and in the spinecurvature of the spine (scoliosis), or a height loss where the bones in the spine have become squashed or misshapen. What are the causes? Primary juvenile osteoporosis is described as bone density loss in a previously healthy child/teenager with a history of bone breaks (arms, legs or spine) for no apparent reason. It is ‘idopathic’ because there is no known cause. Secondary juvenile osteoporosis occurs due to other reasons such as another illness or a medication. Including: inflammatory conditions (such as juvenile arthritis (see entry Arthritis (Juvenile Idiopathic)) or Crohn’s disease (see entry Crohn’s and Ulcerative Colitis))anorexia nervosa (see entry Eating disorders)long-term, high-dose oral corticosteroid treatmentosteogenesis imperfecta (OI) (see entry Brittle Bone disease) – a genetic disorder that affects the collagen, which is an important part of boneconditions causing immobility for example spinal cord injury and cerebral palsy. How is it diagnosed? Juvenile osteoporosis may be discovered when other problems are investigated, such as fractures or difficulty walking. Children will probably be referred to a specialist for further assessment, which can include: X-rays to examine the skeleton for fracturesdual energy x-ray absorptiometry (DXA) – bone density scans to assess the degree of bone density loss. Sometimes other types of scan are used, such as quantitative computerised tomography (QCT or CT)bone biopsies, removal of a small amount of bone tissue, to look at the internal structure of the bone. How is it treated? Parents of children with osteoporosis will be advised to ensure the child has a well-balanced, calcium-rich diet and do plenty of weight-bearing exercise. Physiotherapy may be advised in some children to aid mobility. Some children may need medication that is used in adults with osteoporosis but at smaller doses. Examples include bisphosphonate (drugs that affect the bone cells and the ongoing process of bone renewal) or forms of vitamin D to influence the body’s absorption of calcium. Monitoring will be needed to check the child’s bone density and how the condition is progressing in light of treatment. Inheritance patterns and prenatal diagnosis Inheritance patternsJuvenile osteoporosis has been recognised as more likely to occur in some families, but a genetic cause has not been fully established. Prenatal diagnosisNot applicable. Is there support? Royal Osteoporosis Society Helpline: 0808 800 0035Email: [email protected]Website: theros.org.uk The Society is a Registered Charity in England and Wales No. 11022712. It offers information and support to anyone affected by osteoporosis, including providing information about osteoporosis in children. The Society has a network of support groups across the UK. Group details last updated June 2021.
What are the symptoms? Symptoms will vary from child to child, but may include: pain in the bone often in the back, hips, legs and feetdifficulty in walkingfractures (broken bones) in the long bones of the skeleton and in the spinecurvature of the spine (scoliosis), or a height loss where the bones in the spine have become squashed or misshapen.
What are the causes? Primary juvenile osteoporosis is described as bone density loss in a previously healthy child/teenager with a history of bone breaks (arms, legs or spine) for no apparent reason. It is ‘idopathic’ because there is no known cause. Secondary juvenile osteoporosis occurs due to other reasons such as another illness or a medication. Including: inflammatory conditions (such as juvenile arthritis (see entry Arthritis (Juvenile Idiopathic)) or Crohn’s disease (see entry Crohn’s and Ulcerative Colitis))anorexia nervosa (see entry Eating disorders)long-term, high-dose oral corticosteroid treatmentosteogenesis imperfecta (OI) (see entry Brittle Bone disease) – a genetic disorder that affects the collagen, which is an important part of boneconditions causing immobility for example spinal cord injury and cerebral palsy.
How is it diagnosed? Juvenile osteoporosis may be discovered when other problems are investigated, such as fractures or difficulty walking. Children will probably be referred to a specialist for further assessment, which can include: X-rays to examine the skeleton for fracturesdual energy x-ray absorptiometry (DXA) – bone density scans to assess the degree of bone density loss. Sometimes other types of scan are used, such as quantitative computerised tomography (QCT or CT)bone biopsies, removal of a small amount of bone tissue, to look at the internal structure of the bone.
How is it treated? Parents of children with osteoporosis will be advised to ensure the child has a well-balanced, calcium-rich diet and do plenty of weight-bearing exercise. Physiotherapy may be advised in some children to aid mobility. Some children may need medication that is used in adults with osteoporosis but at smaller doses. Examples include bisphosphonate (drugs that affect the bone cells and the ongoing process of bone renewal) or forms of vitamin D to influence the body’s absorption of calcium. Monitoring will be needed to check the child’s bone density and how the condition is progressing in light of treatment.
Inheritance patterns and prenatal diagnosis Inheritance patternsJuvenile osteoporosis has been recognised as more likely to occur in some families, but a genetic cause has not been fully established. Prenatal diagnosisNot applicable.
Is there support? Royal Osteoporosis Society Helpline: 0808 800 0035Email: [email protected]Website: theros.org.uk The Society is a Registered Charity in England and Wales No. 11022712. It offers information and support to anyone affected by osteoporosis, including providing information about osteoporosis in children. The Society has a network of support groups across the UK. Group details last updated June 2021.
Background Osteopetrosis is a general name for a group of rare genetic diseases which are all characterised by increased bone density. These result from problems in the formation or function of osteoclasts, cells which dissolve bone so that it can be reshaped during growth or repaired after injury. The dense bones are prone to fracturing easily. Nerves which pass through channels in bone (such as the nerves that pass through the skull to the eye or ear) can be damaged, since these channels do not enlarge as the nerves grow; this can affect vision or hearing. Credits Medical text written February 2017 by Professor Colin Steward, Consultant in BMT for Metabolic and Genetic Diseases, Royal Hospital for Children, Bristol, UK and Medical Adviser to the Osteopetrosis Support Trust. Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional. What are the symptoms? Infantile (‘malignant’) osteopetrosis is the most severe form of the disease. Affected children tend to be short but with relatively large heads. They often sustain birth fractures and may be jittery or have convulsions during the first month of life due to hypocalcaemia (low blood calcium). Subsequently, they develop persistent snuffles (due to narrow nasal passages) and are prone to suffer increased ear, nose and throat, and respiratory infections. Bone marrow cavities are reduced: blood then accumulates in the liver and spleen, causing swelling of these organs and a low blood count may result. Many children become blind (see entry Vision disorders in Childhood) by six months of age, deaf (see entry Deafness) and later may develop hydrocephalus. Tooth eruption may be delayed and tooth quality tends to be poor. Adult (‘benign’) osteopetrosis is most commonly diagnosed in late adolescence or early adulthood when bones are X-rayed due to a fracture, although it can sometimes be diagnosed in younger children especially where it is an incidental finding on an X-ray. Some people may go on to develop bone pain, dental problems and deafness or facial nerve paralysis. There is currently no specific treatment. What are the causes? It is now known that mutation in one of more than 10 different genes is responsible for three quarters of cases; the cause remains unknown in the remainder. These genes include those which code for a proton pump (TCIRG1, in 50% of those affected), chloride channel (ClCN7), carbonic anhydrase (CAII), OSTM1, RANK (TNFRSF11A), RANK Ligand (TNFSF11), cathepsin K (CTSK), PLEKHM1, SNX10 and NF-kB Essential Modulator (NEMO). How is it treated? Without treatment many affected children die before adolescence. However, at least half of children affected by the disease can be helped by haemopoietic stem cell transplantation (HSCT) using bone marrow, cord blood or peripheral blood stem cells from family or unrelated donors. Stem cells from the blood or bone marrow can give rise to a variety of specialised cells including osteoclasts, allowing replacement of the absent or ineffective osteoclasts that cause the increased bone density. HSCT is very effective for many types of infantile osteopetrosis including the commonest type due to TCIRG1 mutations. Severe brain problems can develop some time after otherwise successful transplants in children with ClCN7 mutations and always develop in those with OSTM1 mutations. Transplantation therefore has an unclear role in ClCN7 disease and must not be performed in OSTM1 disease. It also does not work for children whose disease is caused by TNFSF11 mutations and has not been reported in autosomal dominant osteopetrosis (ADO) disease. Expert assessment and genetic analysis is therefore important if inappropriate transplantation is to be avoided. Injections of gamma interferon may be effective in alleviating some symptoms of the disease, but are not widely used. Inheritance patterns and prenatal diagnosis Inheritance patternsAutosomal recessive disease may result from mutation of any of 10 or more genes identified as causing osteopetrosis. A total of 50 per cent of babies/infants with osteopetrosis will have mutations of TCIRG1 and 15 per cent will have mutations of ClCN7. Adult osteopetrosis is usually due to dominant mutations of ClCN7, and is therefore termed autosomal dominant osteopetrosis (ADO). Prenatal diagnosisAccurate prenatal diagnosis is possible in families with known gene mutations by either chorionic villus sampling or amniocentesis from ten weeks of pregnancy onwards. For other families prenatal diagnosis is less reliable and depends on detection of changes in the fetus by X-ray or ultrasound in the last third of pregnancy; both tests may still fail to detect accurately affected fetuses. Is there support? Osteopetrosis Support Trust Email: [email protected]Website: osteopetrosis-support-trust.org.uk The Osteopetrosis Support Trust is a parent run support group for families with children affected by Osteopetrosis. They provide information and support, aim to raise awareness of the condition and promote scientific research. Group details updated January 2018.
What are the symptoms? Infantile (‘malignant’) osteopetrosis is the most severe form of the disease. Affected children tend to be short but with relatively large heads. They often sustain birth fractures and may be jittery or have convulsions during the first month of life due to hypocalcaemia (low blood calcium). Subsequently, they develop persistent snuffles (due to narrow nasal passages) and are prone to suffer increased ear, nose and throat, and respiratory infections. Bone marrow cavities are reduced: blood then accumulates in the liver and spleen, causing swelling of these organs and a low blood count may result. Many children become blind (see entry Vision disorders in Childhood) by six months of age, deaf (see entry Deafness) and later may develop hydrocephalus. Tooth eruption may be delayed and tooth quality tends to be poor. Adult (‘benign’) osteopetrosis is most commonly diagnosed in late adolescence or early adulthood when bones are X-rayed due to a fracture, although it can sometimes be diagnosed in younger children especially where it is an incidental finding on an X-ray. Some people may go on to develop bone pain, dental problems and deafness or facial nerve paralysis. There is currently no specific treatment. What are the causes? It is now known that mutation in one of more than 10 different genes is responsible for three quarters of cases; the cause remains unknown in the remainder. These genes include those which code for a proton pump (TCIRG1, in 50% of those affected), chloride channel (ClCN7), carbonic anhydrase (CAII), OSTM1, RANK (TNFRSF11A), RANK Ligand (TNFSF11), cathepsin K (CTSK), PLEKHM1, SNX10 and NF-kB Essential Modulator (NEMO). How is it treated? Without treatment many affected children die before adolescence. However, at least half of children affected by the disease can be helped by haemopoietic stem cell transplantation (HSCT) using bone marrow, cord blood or peripheral blood stem cells from family or unrelated donors. Stem cells from the blood or bone marrow can give rise to a variety of specialised cells including osteoclasts, allowing replacement of the absent or ineffective osteoclasts that cause the increased bone density. HSCT is very effective for many types of infantile osteopetrosis including the commonest type due to TCIRG1 mutations. Severe brain problems can develop some time after otherwise successful transplants in children with ClCN7 mutations and always develop in those with OSTM1 mutations. Transplantation therefore has an unclear role in ClCN7 disease and must not be performed in OSTM1 disease. It also does not work for children whose disease is caused by TNFSF11 mutations and has not been reported in autosomal dominant osteopetrosis (ADO) disease. Expert assessment and genetic analysis is therefore important if inappropriate transplantation is to be avoided. Injections of gamma interferon may be effective in alleviating some symptoms of the disease, but are not widely used. Inheritance patterns and prenatal diagnosis Inheritance patternsAutosomal recessive disease may result from mutation of any of 10 or more genes identified as causing osteopetrosis. A total of 50 per cent of babies/infants with osteopetrosis will have mutations of TCIRG1 and 15 per cent will have mutations of ClCN7. Adult osteopetrosis is usually due to dominant mutations of ClCN7, and is therefore termed autosomal dominant osteopetrosis (ADO). Prenatal diagnosisAccurate prenatal diagnosis is possible in families with known gene mutations by either chorionic villus sampling or amniocentesis from ten weeks of pregnancy onwards. For other families prenatal diagnosis is less reliable and depends on detection of changes in the fetus by X-ray or ultrasound in the last third of pregnancy; both tests may still fail to detect accurately affected fetuses. Is there support? Osteopetrosis Support Trust Email: [email protected]Website: osteopetrosis-support-trust.org.uk The Osteopetrosis Support Trust is a parent run support group for families with children affected by Osteopetrosis. They provide information and support, aim to raise awareness of the condition and promote scientific research. Group details updated January 2018.
What are the symptoms? Infantile (‘malignant’) osteopetrosis is the most severe form of the disease. Affected children tend to be short but with relatively large heads. They often sustain birth fractures and may be jittery or have convulsions during the first month of life due to hypocalcaemia (low blood calcium). Subsequently, they develop persistent snuffles (due to narrow nasal passages) and are prone to suffer increased ear, nose and throat, and respiratory infections. Bone marrow cavities are reduced: blood then accumulates in the liver and spleen, causing swelling of these organs and a low blood count may result. Many children become blind (see entry Vision disorders in Childhood) by six months of age, deaf (see entry Deafness) and later may develop hydrocephalus. Tooth eruption may be delayed and tooth quality tends to be poor. Adult (‘benign’) osteopetrosis is most commonly diagnosed in late adolescence or early adulthood when bones are X-rayed due to a fracture, although it can sometimes be diagnosed in younger children especially where it is an incidental finding on an X-ray. Some people may go on to develop bone pain, dental problems and deafness or facial nerve paralysis. There is currently no specific treatment.
What are the causes? It is now known that mutation in one of more than 10 different genes is responsible for three quarters of cases; the cause remains unknown in the remainder. These genes include those which code for a proton pump (TCIRG1, in 50% of those affected), chloride channel (ClCN7), carbonic anhydrase (CAII), OSTM1, RANK (TNFRSF11A), RANK Ligand (TNFSF11), cathepsin K (CTSK), PLEKHM1, SNX10 and NF-kB Essential Modulator (NEMO).
How is it treated? Without treatment many affected children die before adolescence. However, at least half of children affected by the disease can be helped by haemopoietic stem cell transplantation (HSCT) using bone marrow, cord blood or peripheral blood stem cells from family or unrelated donors. Stem cells from the blood or bone marrow can give rise to a variety of specialised cells including osteoclasts, allowing replacement of the absent or ineffective osteoclasts that cause the increased bone density. HSCT is very effective for many types of infantile osteopetrosis including the commonest type due to TCIRG1 mutations. Severe brain problems can develop some time after otherwise successful transplants in children with ClCN7 mutations and always develop in those with OSTM1 mutations. Transplantation therefore has an unclear role in ClCN7 disease and must not be performed in OSTM1 disease. It also does not work for children whose disease is caused by TNFSF11 mutations and has not been reported in autosomal dominant osteopetrosis (ADO) disease. Expert assessment and genetic analysis is therefore important if inappropriate transplantation is to be avoided. Injections of gamma interferon may be effective in alleviating some symptoms of the disease, but are not widely used.
Inheritance patterns and prenatal diagnosis Inheritance patternsAutosomal recessive disease may result from mutation of any of 10 or more genes identified as causing osteopetrosis. A total of 50 per cent of babies/infants with osteopetrosis will have mutations of TCIRG1 and 15 per cent will have mutations of ClCN7. Adult osteopetrosis is usually due to dominant mutations of ClCN7, and is therefore termed autosomal dominant osteopetrosis (ADO). Prenatal diagnosisAccurate prenatal diagnosis is possible in families with known gene mutations by either chorionic villus sampling or amniocentesis from ten weeks of pregnancy onwards. For other families prenatal diagnosis is less reliable and depends on detection of changes in the fetus by X-ray or ultrasound in the last third of pregnancy; both tests may still fail to detect accurately affected fetuses.
Is there support? Osteopetrosis Support Trust Email: [email protected]Website: osteopetrosis-support-trust.org.uk The Osteopetrosis Support Trust is a parent run support group for families with children affected by Osteopetrosis. They provide information and support, aim to raise awareness of the condition and promote scientific research. Group details updated January 2018.
Background The organic acidaemias (also known as organic acidurias) are a group of inherited conditions that affect the way the body is able to break down (metabolise) amino acids (the building blocks of body protein). Credits Last updated March 2019 by Dr Elisabeth Jameson , Consultant Paediatrician, Inherited Metabolic Disease, Willink Biochemical Genetics Unit, Genetic Medicine, Manchester Academic Health Science Centre, Manchester, UK. Although great care has been taken in the compilation and preparation of all entries to ensure accuracy, we cannot accept responsibility for any errors or omissions. Any medical information provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional. What are the symptoms? Before birth, a baby with an organic acidaemia is usually protected from harm as the placenta is able to remove any harmful acids. Soon after delivery, these acids begin to accumulate and may cause a severe illness. Characteristic symptoms include: drowsinessreluctance to feedbreathing problems (usually fast breathing)vomitinghypotonia (floppiness)and/or spasticity (stiffness). What are the causes? In each condition, there is a deficiency of a particular enzyme involved in the breakdown of one or more amino acids due to a genetic change (mutation) that means the enzyme is not made properly. This leads to a build-up of harmful acidic chemicals in the body. Individual disorders are usually named after the type of chemical that accumulates in the blood or urine or, alternatively, according to the enzyme that is deficient. For example, in propionic acidaemia there is an accumulation of propionic acid in blood but the condition is also called propionyl-CoA carboxylase deficiency, since it is the enzyme propionyl-CoA carboxylase that is deficient. The other most common organic acidaemias are methylmalonic acidaemia and isovaleric acidaemia. How is it diagnosed? The diagnosis is most often made by finding high levels of characteristic chemicals in urine by a scientific technique called gas chromatography/mass spectrometry (GCMS) and in blood using another technique called tandem mass spectrometry (TMS). The diagnosis can then be confirmed by doing special enzyme studies and by DNA tests. Isovaleric acidaemia is now tested for on the new born heel prick test done on day 5 of life. How is it treated? Treatment is directed at trying to prevent the accumulation of the harmful acidic chemicals by reducing the intake of protein in the diet, while ensuring the diet is nutritionally complete, and increasing the removal of acidic chemicals using various medicines. The patients are also given an emergency regimen consisting of a glucose polymer drink that they must take when they are unwell. Unfortunately, there is no cure for any of the organic acidaemias because the defect in the manufacture of the particular enzyme is permanent and no effective enzyme replacement is yet available. Treatment may be effective in those with less severe symptoms but, unfortunately, for those with a more severe disease, long-term complications are common and may be life-threatening. Inheritance patterns and prenatal diagnosis Inheritance patternsThese conditions are inherited in an autosomal recessive manner and are life long. This means parents of children with an organic acidaemia will each have one normal and one abnormal gene. One normal gene makes enough enzyme so that parents do not have the disorder themselves. However, at the time of conception there is a 1 in 4 chance or 25% chance their baby will have inherited both the abnormal genes from his/her parents. Affected families should be referred to a genetics centre for advice and support. Prenatal diagnosisPrenatal testing is available. Testing is carried out using chorionic villus sampling but amniocentesis may also be used. Is there support? Information and support in the UK for organic acidaemias is provided by Metabolic UK (see entry Inherited Metabolic diseases).
What are the symptoms? Before birth, a baby with an organic acidaemia is usually protected from harm as the placenta is able to remove any harmful acids. Soon after delivery, these acids begin to accumulate and may cause a severe illness. Characteristic symptoms include: drowsinessreluctance to feedbreathing problems (usually fast breathing)vomitinghypotonia (floppiness)and/or spasticity (stiffness). What are the causes? In each condition, there is a deficiency of a particular enzyme involved in the breakdown of one or more amino acids due to a genetic change (mutation) that means the enzyme is not made properly. This leads to a build-up of harmful acidic chemicals in the body. Individual disorders are usually named after the type of chemical that accumulates in the blood or urine or, alternatively, according to the enzyme that is deficient. For example, in propionic acidaemia there is an accumulation of propionic acid in blood but the condition is also called propionyl-CoA carboxylase deficiency, since it is the enzyme propionyl-CoA carboxylase that is deficient. The other most common organic acidaemias are methylmalonic acidaemia and isovaleric acidaemia. How is it diagnosed? The diagnosis is most often made by finding high levels of characteristic chemicals in urine by a scientific technique called gas chromatography/mass spectrometry (GCMS) and in blood using another technique called tandem mass spectrometry (TMS). The diagnosis can then be confirmed by doing special enzyme studies and by DNA tests. Isovaleric acidaemia is now tested for on the new born heel prick test done on day 5 of life. How is it treated? Treatment is directed at trying to prevent the accumulation of the harmful acidic chemicals by reducing the intake of protein in the diet, while ensuring the diet is nutritionally complete, and increasing the removal of acidic chemicals using various medicines. The patients are also given an emergency regimen consisting of a glucose polymer drink that they must take when they are unwell. Unfortunately, there is no cure for any of the organic acidaemias because the defect in the manufacture of the particular enzyme is permanent and no effective enzyme replacement is yet available. Treatment may be effective in those with less severe symptoms but, unfortunately, for those with a more severe disease, long-term complications are common and may be life-threatening. Inheritance patterns and prenatal diagnosis Inheritance patternsThese conditions are inherited in an autosomal recessive manner and are life long. This means parents of children with an organic acidaemia will each have one normal and one abnormal gene. One normal gene makes enough enzyme so that parents do not have the disorder themselves. However, at the time of conception there is a 1 in 4 chance or 25% chance their baby will have inherited both the abnormal genes from his/her parents. Affected families should be referred to a genetics centre for advice and support. Prenatal diagnosisPrenatal testing is available. Testing is carried out using chorionic villus sampling but amniocentesis may also be used. Is there support? Information and support in the UK for organic acidaemias is provided by Metabolic UK (see entry Inherited Metabolic diseases).
What are the symptoms? Before birth, a baby with an organic acidaemia is usually protected from harm as the placenta is able to remove any harmful acids. Soon after delivery, these acids begin to accumulate and may cause a severe illness. Characteristic symptoms include: drowsinessreluctance to feedbreathing problems (usually fast breathing)vomitinghypotonia (floppiness)and/or spasticity (stiffness).
What are the causes? In each condition, there is a deficiency of a particular enzyme involved in the breakdown of one or more amino acids due to a genetic change (mutation) that means the enzyme is not made properly. This leads to a build-up of harmful acidic chemicals in the body. Individual disorders are usually named after the type of chemical that accumulates in the blood or urine or, alternatively, according to the enzyme that is deficient. For example, in propionic acidaemia there is an accumulation of propionic acid in blood but the condition is also called propionyl-CoA carboxylase deficiency, since it is the enzyme propionyl-CoA carboxylase that is deficient. The other most common organic acidaemias are methylmalonic acidaemia and isovaleric acidaemia.
How is it diagnosed? The diagnosis is most often made by finding high levels of characteristic chemicals in urine by a scientific technique called gas chromatography/mass spectrometry (GCMS) and in blood using another technique called tandem mass spectrometry (TMS). The diagnosis can then be confirmed by doing special enzyme studies and by DNA tests. Isovaleric acidaemia is now tested for on the new born heel prick test done on day 5 of life.
How is it treated? Treatment is directed at trying to prevent the accumulation of the harmful acidic chemicals by reducing the intake of protein in the diet, while ensuring the diet is nutritionally complete, and increasing the removal of acidic chemicals using various medicines. The patients are also given an emergency regimen consisting of a glucose polymer drink that they must take when they are unwell. Unfortunately, there is no cure for any of the organic acidaemias because the defect in the manufacture of the particular enzyme is permanent and no effective enzyme replacement is yet available. Treatment may be effective in those with less severe symptoms but, unfortunately, for those with a more severe disease, long-term complications are common and may be life-threatening.
Inheritance patterns and prenatal diagnosis Inheritance patternsThese conditions are inherited in an autosomal recessive manner and are life long. This means parents of children with an organic acidaemia will each have one normal and one abnormal gene. One normal gene makes enough enzyme so that parents do not have the disorder themselves. However, at the time of conception there is a 1 in 4 chance or 25% chance their baby will have inherited both the abnormal genes from his/her parents. Affected families should be referred to a genetics centre for advice and support. Prenatal diagnosisPrenatal testing is available. Testing is carried out using chorionic villus sampling but amniocentesis may also be used.
Is there support? Information and support in the UK for organic acidaemias is provided by Metabolic UK (see entry Inherited Metabolic diseases).
Also known as: Enchondromatosis Overview Ollier’s disease is a condition where several enchondromas exist in the bone. These may affect a single digit, part of a hand or foot, a whole limb, one side of the body or the whole body. An enchondroma is a benign (non-cancerous) tumour consisting of cartilage (which is a flexible connective tissue). The main complications relate to of the presence of the cartilage tissue within the bone resulting in deformity and/or shortening of the affected bone. Fractures can also occur. There may also be problems with curving of the spine (scoliosis). Ollier’s disease can be diagnosed based on clinical features and X-rays. Malignancy (becoming cancerous) of enchondromas can occur, but it is extremely rare. The bone deformity can be corrected by osteotomy (where the bone is cut to shorten, lengthen, or change its alignment) and the shortening can be addressed by leg lengthening. Pain in enchondromas should be a warning sign to parents to take the child for investigation. Although classified as a genetic condition, it is not inherited. Hence affected people cannot pass it on to their children, neither are their brothers or sisters at risk. This overview is intended to be a basic description of the condition. It is not intended to replace specialist medical advice. We advise that you discuss your child’s case with a qualified medical professional who will be able to give you more detailed information. Credits Medical text approved November 2012 by Dr Daniel Porter, Contact Medical Advisory Panel. Is there support? Olliers Global Support Email: [email protected] Olliers Global Support was established in 1999. It offers information and support, and the opportunity to contact other families affected by Olliers disease and Maffucci syndrome. The Organisation is in contact with orthopaedic and plastic surgeons in the UK and abroad. It has two members-only Facebook support groups: Olliers & Maffucci Global Support and parents, and Olliers Owls and Maffucci Meerkats for children and young people. Group details last updated April 2019.
Is there support? Olliers Global Support Email: [email protected] Olliers Global Support was established in 1999. It offers information and support, and the opportunity to contact other families affected by Olliers disease and Maffucci syndrome. The Organisation is in contact with orthopaedic and plastic surgeons in the UK and abroad. It has two members-only Facebook support groups: Olliers & Maffucci Global Support and parents, and Olliers Owls and Maffucci Meerkats for children and young people. Group details last updated April 2019.
Is there support? Olliers Global Support Email: [email protected] Olliers Global Support was established in 1999. It offers information and support, and the opportunity to contact other families affected by Olliers disease and Maffucci syndrome. The Organisation is in contact with orthopaedic and plastic surgeons in the UK and abroad. It has two members-only Facebook support groups: Olliers & Maffucci Global Support and parents, and Olliers Owls and Maffucci Meerkats for children and young people. Group details last updated April 2019.
Also known as: Optic Nerve Head Hypoplasia Optic nerve hypoplasia (ONH) is a congenital condition (present at birth) in which there is underdevelopment of the optic nerve. ONH can be unilateral (affecting one eye) or bilateral (affecting both eyes) and occurs in both males and females. ONH is thought to be one of the three most common causes of visual impairment in children. In this article What are the symptoms of Optic Nerve Hypoplasia? The optic nerve carries visual information from the eye to the brain, which interprets it and allows people to ‘see’ objects and the surrounding world. This process can be interrupted to a greater or lesser degree depending on the amount of underdevelopment of the optic nerve. If the nerve in only one eye is affected in a minor way vision can be almost normal but if both eyes are affected in a more major way, the individual may only be able to see large objects and in severe cases not to see even a bright light. Other ocular features of ONH may include: nystagmus mild photophobia (light sensitivity) problems of peripheral vision (inability to see objects to the side of vision) poor depth perception (reduced ability to judge distances). ONH may also be associated with other conditions such as septo-optic dysplasia, which is due to incorrect development of the pituitary gland and if visual impairment is severe with disrupted sleep pattern. What are the causes of Optic Nerve Hypoplasia? ONH is likely to be due to a variety of causes. The cause of most cases of ONH is not known but in a few cases there may be an association with maternal diabetes (see entry Diabetes Mellitus), maternal weight loss during pregnancy and vaginal bleeding early in pregnancy. It is believed that, at some stage of the growth of the fetus, there is a loss of nerve fibre resulting in underdevelopment of the optic nerve. How is Optic Nerve Hypoplasia diagnosed? ONH is diagnosed on examination of the optic disc by a doctor looking into the eye with an ophthalmoscope and seeing the size of the optic nerve head. In some cases it may be difficult to be sure that the nerve is small especially if the baby is very young or very wriggly during the examination. It can be helpful to look at the size of the optic nerve behind the eye on a magnetic resonance imaging (MRI) brain scan. This examination also is helpful as other structures may be small such as the pituitary gland. Electrodiagnostic testing of the visual evoked potential (electrical signal received in the brain from the eye) can sometimes be helpful in very small children to give an idea of a child’s potential vision and prognosis. How is Optic Nerve Hypoplasia treated? There is no cure for ONH and treatment is symptomatic for the specific difficulties it causes. This is a non-progressive condition, which means that any vision that does develop is not later lost due to ONH. Even if an infant seems to be blind, vision may still develop over the first couple of years and a programme encouraging a child to ‘fix and follow’ bright toys and lights may be helpful. Families and teachers can help children by providing appropriately sized books and toys. Children with ONH often have to learn aspects of vision, depth and perception to allow them to play and carry out many of the ordinary activities of childhood. Families can provide important assistance by teaching activities such as using slides, climbing stairs and water play. Ongoing assessment of a child’s needs and educational path should take place. The Developmental Journal for babies and children with visual impairment encourages families to record and celebrate their child’s learning and development through the early years. Inheritance patterns and prenatal diagnosis Inheritance patternsMost cases of ONH occur sporadically without any other family members being affected. Prenatal diagnosisONH is very rarely inherited. Prenatal diagnosis is not available. However, it is possible to image the septum pellucidum (a structure in the brain) antenatally by ultrasound. Absence of this structure may be an indicator of ONH. Obstetricians should be made aware if a previous sibling has ONH so that this can be checked carefully, although absence of the structure is not necessarily associated with ONH. Is there support for people affected by Optic Nerve Hypoplasia and their families? If your child is affected by a medical condition or disability, we can help. Call our freephone helpline on 0808 808 3555 to get information, support and advice. We also offer emotional support for parents via our Listening Ear service. We have a range of parent guides on aspects of caring for a disabled child in our resource library. You may also find our Early Years Support useful, which contains links to parent carer workshops and help for families going through the diagnosis process. You can also meet other parents online in our closed Facebook group. Credits Medical text written October 2005 by Miss Isabelle Russell-Eggitt. Last updated October 2010 by Isabelle Russell-Eggitt, Consultant Ophthalmic Surgeon, Great Ormond Street Hospital, London, UK.
Also known as: Keller syndrome; Opitz FG syndrome; Opitz-Kaveggia syndrome Background FG syndrome was first described by Professor Opitz and Dr Kaveggia in 1974. It became known as FG syndrome according to the system used at that time by Dr Opitz, who preferred to name conditions with the initials of the names of the first presenting families, rather than eponymously, after the name of the doctors who wrote the first medical reports. Nevertheless, the Opitz-Kaveggia name is now preferred by some doctors and the name Keller syndrome is a name that is seldom used. Note that Opitz-Kaveggia/FG syndrome has subtle clinical and important genetic differences from the Opitz G/BBB syndrome. Credits Medical text written August 2005 by Contact a Family. Approved August 2005 by Dr J Tolmie, Last updated August 2007 by Contact a Family and by Dr J Tolmie, Consultant Clinical Geneticist, Ferguson-Smith Centre for Clinical Genetics, Glasgow, UK. What are the symptoms? The main signs and symptoms of Opitz-Kaveggia/FG affect male infants and include hypotonia (reduced muscle tone) with global developmental delay and subsequent learning disability; imperforate or narrowed anus (skin covered or blocked bottom) or severe constipation; high prominent forehead with larger than average head circumference and somewhat widened and flattened-appearing thumbs and great toes. Brain scan may show a lesion called agenesis of the corpus callosum that is not in itself harmful. As the imperforate anus is not present in each case and constipation is a non-specific sign, Opitz-Kaveggia/FG can be hard to diagnose and it may therefore have gone unrecognised in the past. As mentioned above, the clinical features of FG syndrome can vary in different affected individuals and can include: learning disability in males imperforate anus or severe constipation reduced or lax muscle tone in childhood; increased tone in adulthood minor changes in appearance such as high broad forehead with upsweep of the hairline (cow’s lick), wide-apart eyes, smallish external ears, broad thumbs and great toes congenital heart defect (see entry, Heart Defects) short stature (see entry Restricted Growth) seizures (see entry Epilepsy) hearing loss (see entry Deafness) hyperactivity and tantrums (see entry Attention Deficit Hyperactivity disorder) friendly or outgoing personality. What are the causes? Opitz-Kaveggia/ FG syndrome is sometimes due to a mutation in a gene called MED12 that is located on the X chromosome. Female carriers are generally unaffected but a few carriers may have some symptoms or signs. Because MED12 gene mutations have been identified recently, DNA-based postnatal and prenatal diagnosis may be possible in the future in some but not all families. How is it diagnosed? Diagnosis of Opitz-Kaveggia/FG syndrome is usually made by observation of affected individuals with clinical features of the disorder, and its inheritance in an X-chromosome linked fashion within the family lends further support. Affected families should be offered genetic counselling. How is it treated? Multidisciplinary treatments and support are required for the child who has complex or severe learning disabilities and surgical treatment is required to correct an imperforate or narrowed anus. Inheritance patterns and prenatal diagnosis Inheritance patternsX-chromosome linked but it is likely that there is more than one FG syndrome gene on the X-chromosome. Prenatal diagnosisThis will be possible by DNA testing if the Opitz-Kaveggia/FG syndrome gene mutation has already been identified in an affected relative. Otherwise, an affected fetus might be identified in mid-pregnancy through identification by a detailed ultrasound examination of a particular pattern of abnormalities including a corpus callosum (structure in the brain) abnormality. Is there support? There is no support group for Opitz-Kaveggia/FG syndrome in the UK. Families can also use Contact’s freephone helpline for advice and information. To meet other families with disabled children, join Contact’s closed (private) Facebook group.
What are the symptoms? The main signs and symptoms of Opitz-Kaveggia/FG affect male infants and include hypotonia (reduced muscle tone) with global developmental delay and subsequent learning disability; imperforate or narrowed anus (skin covered or blocked bottom) or severe constipation; high prominent forehead with larger than average head circumference and somewhat widened and flattened-appearing thumbs and great toes. Brain scan may show a lesion called agenesis of the corpus callosum that is not in itself harmful. As the imperforate anus is not present in each case and constipation is a non-specific sign, Opitz-Kaveggia/FG can be hard to diagnose and it may therefore have gone unrecognised in the past. As mentioned above, the clinical features of FG syndrome can vary in different affected individuals and can include: learning disability in males imperforate anus or severe constipation reduced or lax muscle tone in childhood; increased tone in adulthood minor changes in appearance such as high broad forehead with upsweep of the hairline (cow’s lick), wide-apart eyes, smallish external ears, broad thumbs and great toes congenital heart defect (see entry, Heart Defects) short stature (see entry Restricted Growth) seizures (see entry Epilepsy) hearing loss (see entry Deafness) hyperactivity and tantrums (see entry Attention Deficit Hyperactivity disorder) friendly or outgoing personality. What are the causes? Opitz-Kaveggia/ FG syndrome is sometimes due to a mutation in a gene called MED12 that is located on the X chromosome. Female carriers are generally unaffected but a few carriers may have some symptoms or signs. Because MED12 gene mutations have been identified recently, DNA-based postnatal and prenatal diagnosis may be possible in the future in some but not all families. How is it diagnosed? Diagnosis of Opitz-Kaveggia/FG syndrome is usually made by observation of affected individuals with clinical features of the disorder, and its inheritance in an X-chromosome linked fashion within the family lends further support. Affected families should be offered genetic counselling. How is it treated? Multidisciplinary treatments and support are required for the child who has complex or severe learning disabilities and surgical treatment is required to correct an imperforate or narrowed anus. Inheritance patterns and prenatal diagnosis Inheritance patternsX-chromosome linked but it is likely that there is more than one FG syndrome gene on the X-chromosome. Prenatal diagnosisThis will be possible by DNA testing if the Opitz-Kaveggia/FG syndrome gene mutation has already been identified in an affected relative. Otherwise, an affected fetus might be identified in mid-pregnancy through identification by a detailed ultrasound examination of a particular pattern of abnormalities including a corpus callosum (structure in the brain) abnormality. Is there support? There is no support group for Opitz-Kaveggia/FG syndrome in the UK. Families can also use Contact’s freephone helpline for advice and information. To meet other families with disabled children, join Contact’s closed (private) Facebook group.
What are the symptoms? The main signs and symptoms of Opitz-Kaveggia/FG affect male infants and include hypotonia (reduced muscle tone) with global developmental delay and subsequent learning disability; imperforate or narrowed anus (skin covered or blocked bottom) or severe constipation; high prominent forehead with larger than average head circumference and somewhat widened and flattened-appearing thumbs and great toes. Brain scan may show a lesion called agenesis of the corpus callosum that is not in itself harmful. As the imperforate anus is not present in each case and constipation is a non-specific sign, Opitz-Kaveggia/FG can be hard to diagnose and it may therefore have gone unrecognised in the past. As mentioned above, the clinical features of FG syndrome can vary in different affected individuals and can include: learning disability in males imperforate anus or severe constipation reduced or lax muscle tone in childhood; increased tone in adulthood minor changes in appearance such as high broad forehead with upsweep of the hairline (cow’s lick), wide-apart eyes, smallish external ears, broad thumbs and great toes congenital heart defect (see entry, Heart Defects) short stature (see entry Restricted Growth) seizures (see entry Epilepsy) hearing loss (see entry Deafness) hyperactivity and tantrums (see entry Attention Deficit Hyperactivity disorder) friendly or outgoing personality.
What are the causes? Opitz-Kaveggia/ FG syndrome is sometimes due to a mutation in a gene called MED12 that is located on the X chromosome. Female carriers are generally unaffected but a few carriers may have some symptoms or signs. Because MED12 gene mutations have been identified recently, DNA-based postnatal and prenatal diagnosis may be possible in the future in some but not all families.
How is it diagnosed? Diagnosis of Opitz-Kaveggia/FG syndrome is usually made by observation of affected individuals with clinical features of the disorder, and its inheritance in an X-chromosome linked fashion within the family lends further support. Affected families should be offered genetic counselling.
How is it treated? Multidisciplinary treatments and support are required for the child who has complex or severe learning disabilities and surgical treatment is required to correct an imperforate or narrowed anus.
Inheritance patterns and prenatal diagnosis Inheritance patternsX-chromosome linked but it is likely that there is more than one FG syndrome gene on the X-chromosome. Prenatal diagnosisThis will be possible by DNA testing if the Opitz-Kaveggia/FG syndrome gene mutation has already been identified in an affected relative. Otherwise, an affected fetus might be identified in mid-pregnancy through identification by a detailed ultrasound examination of a particular pattern of abnormalities including a corpus callosum (structure in the brain) abnormality.
Is there support? There is no support group for Opitz-Kaveggia/FG syndrome in the UK. Families can also use Contact’s freephone helpline for advice and information. To meet other families with disabled children, join Contact’s closed (private) Facebook group.
Also known as: G syndrome; Hypertelorism-Hypospadias syndrome; Opitz-Frias syndrome Background Professor John Opitz, an eminent North American geneticist, and colleagues first drew attention to these conditions in 1969 and subsequently. Professor Opitz did not wish to follow the practice of naming syndromes after the medical authors who report the condition, so he suggested conditions are represented by the initials of the names of families who first present. However, with an increasing number of newly reported syndromes, this system fell out of favour. Credits Medical text written October 2001 by Dr J Tolmie. Last updated September 2007 by Dr J Tolmie, Consultant Clinical Geneticist, Ferguson-Smith Centre for Clinical Genetics, Glasgow, UK. What are the symptoms? In Opitz G/BBB syndrome the clinical features mainly affect midline structures of the body. Increased spacing between the eyes (hypertelorism) is often apparent but this is less important than difficulties in swallowing or breathing due to malformation of the larynx (voicebox), trachea (the main airway), or oesophagus (the gullet), or bottom (imperforate anus). Kidney abnormalities (Kidney disease) and hypospadias (displacement of the orifice at the tip of the penis) are common. Other complications are present less frequently. What are the causes? It is now generally agreed that Opitz G/BBB syndromes are clinically indistinguishable, but it is likely that, in different families, the condition may arise from different genetic changes. This phenomenon is termed genetic heterogeneity and it is important for families because it complicates genetic risk prediction and makes gene testing more difficult. Probably, there is an Opitz G/BBB gene fault or mutation located on chromosome 22. In a few cases only, a larger chromosome 22q11 deletion has been diagnosed by a special (FISH) chromosome test. In yet other families, the Opitz G/BBB syndrome gene is located at the tip of the X chromosome in a gene called midline (MID1). Note that the Opitz G/BBB syndrome is different from another X chromosome condition called Opitz-Kaveggia/FG syndrome, which is sometimes caused by a change in the MED12 gene. How is it diagnosed? Diagnosis of Opitz-Kaveggia/FG syndrome is usually made by observation of affected individuals with clinical features of the disorder, and its inheritance in an X-chromosome linked fashion within the family lends further support. Affected families should be offered genetic counselling. How is it treated? Multidisciplinary treatments and support are required for the child who has complex or severe learning disabilities and surgical treatment is required to correct an imperforate or narrowed anus. Inheritance patterns and prenatal diagnosis Inheritance patternsThis may be very difficult to assess, especially if only one person in a family is affected. Specialist genetic counselling is advisable. Without evidence from the family tree, it might be difficult to estimate the risk of recurrence of the syndrome in a family. Parents and other close relatives may need to be examined for minor features of the syndrome. Rarely, the family tree indicates clear-cut autosomal dominant or X-chromosome linked inheritance that carries high risk of recurrence. Prenatal diagnosisGene tests are not routinely available but in some families a causative gene change is identified that does permit prenatal testing after chorion villus sampling or amniocentesis. In other families, prenatal diagnosis by ultrasound examination may demonstrate a rare complication associated with the presence of the syndrome in the fetus. Is there support? Information and support in the UK for the form of Opitz G/BBB resulting from a chromosome 22q11 deletion is provided by Max Appeal (see entry 22q11 Deletion syndromes). Families can use Contact’s freephone helpline for advice and information. To meet other families with disabled children, join Contact’s closed (private) Facebook group.
What are the symptoms? In Opitz G/BBB syndrome the clinical features mainly affect midline structures of the body. Increased spacing between the eyes (hypertelorism) is often apparent but this is less important than difficulties in swallowing or breathing due to malformation of the larynx (voicebox), trachea (the main airway), or oesophagus (the gullet), or bottom (imperforate anus). Kidney abnormalities (Kidney disease) and hypospadias (displacement of the orifice at the tip of the penis) are common. Other complications are present less frequently. What are the causes? It is now generally agreed that Opitz G/BBB syndromes are clinically indistinguishable, but it is likely that, in different families, the condition may arise from different genetic changes. This phenomenon is termed genetic heterogeneity and it is important for families because it complicates genetic risk prediction and makes gene testing more difficult. Probably, there is an Opitz G/BBB gene fault or mutation located on chromosome 22. In a few cases only, a larger chromosome 22q11 deletion has been diagnosed by a special (FISH) chromosome test. In yet other families, the Opitz G/BBB syndrome gene is located at the tip of the X chromosome in a gene called midline (MID1). Note that the Opitz G/BBB syndrome is different from another X chromosome condition called Opitz-Kaveggia/FG syndrome, which is sometimes caused by a change in the MED12 gene. How is it diagnosed? Diagnosis of Opitz-Kaveggia/FG syndrome is usually made by observation of affected individuals with clinical features of the disorder, and its inheritance in an X-chromosome linked fashion within the family lends further support. Affected families should be offered genetic counselling. How is it treated? Multidisciplinary treatments and support are required for the child who has complex or severe learning disabilities and surgical treatment is required to correct an imperforate or narrowed anus. Inheritance patterns and prenatal diagnosis Inheritance patternsThis may be very difficult to assess, especially if only one person in a family is affected. Specialist genetic counselling is advisable. Without evidence from the family tree, it might be difficult to estimate the risk of recurrence of the syndrome in a family. Parents and other close relatives may need to be examined for minor features of the syndrome. Rarely, the family tree indicates clear-cut autosomal dominant or X-chromosome linked inheritance that carries high risk of recurrence. Prenatal diagnosisGene tests are not routinely available but in some families a causative gene change is identified that does permit prenatal testing after chorion villus sampling or amniocentesis. In other families, prenatal diagnosis by ultrasound examination may demonstrate a rare complication associated with the presence of the syndrome in the fetus. Is there support? Information and support in the UK for the form of Opitz G/BBB resulting from a chromosome 22q11 deletion is provided by Max Appeal (see entry 22q11 Deletion syndromes). Families can use Contact’s freephone helpline for advice and information. To meet other families with disabled children, join Contact’s closed (private) Facebook group.
What are the symptoms? In Opitz G/BBB syndrome the clinical features mainly affect midline structures of the body. Increased spacing between the eyes (hypertelorism) is often apparent but this is less important than difficulties in swallowing or breathing due to malformation of the larynx (voicebox), trachea (the main airway), or oesophagus (the gullet), or bottom (imperforate anus). Kidney abnormalities (Kidney disease) and hypospadias (displacement of the orifice at the tip of the penis) are common. Other complications are present less frequently.
What are the causes? It is now generally agreed that Opitz G/BBB syndromes are clinically indistinguishable, but it is likely that, in different families, the condition may arise from different genetic changes. This phenomenon is termed genetic heterogeneity and it is important for families because it complicates genetic risk prediction and makes gene testing more difficult. Probably, there is an Opitz G/BBB gene fault or mutation located on chromosome 22. In a few cases only, a larger chromosome 22q11 deletion has been diagnosed by a special (FISH) chromosome test. In yet other families, the Opitz G/BBB syndrome gene is located at the tip of the X chromosome in a gene called midline (MID1). Note that the Opitz G/BBB syndrome is different from another X chromosome condition called Opitz-Kaveggia/FG syndrome, which is sometimes caused by a change in the MED12 gene.
How is it diagnosed? Diagnosis of Opitz-Kaveggia/FG syndrome is usually made by observation of affected individuals with clinical features of the disorder, and its inheritance in an X-chromosome linked fashion within the family lends further support. Affected families should be offered genetic counselling.
How is it treated? Multidisciplinary treatments and support are required for the child who has complex or severe learning disabilities and surgical treatment is required to correct an imperforate or narrowed anus.
Inheritance patterns and prenatal diagnosis Inheritance patternsThis may be very difficult to assess, especially if only one person in a family is affected. Specialist genetic counselling is advisable. Without evidence from the family tree, it might be difficult to estimate the risk of recurrence of the syndrome in a family. Parents and other close relatives may need to be examined for minor features of the syndrome. Rarely, the family tree indicates clear-cut autosomal dominant or X-chromosome linked inheritance that carries high risk of recurrence. Prenatal diagnosisGene tests are not routinely available but in some families a causative gene change is identified that does permit prenatal testing after chorion villus sampling or amniocentesis. In other families, prenatal diagnosis by ultrasound examination may demonstrate a rare complication associated with the presence of the syndrome in the fetus.
Is there support? Information and support in the UK for the form of Opitz G/BBB resulting from a chromosome 22q11 deletion is provided by Max Appeal (see entry 22q11 Deletion syndromes). Families can use Contact’s freephone helpline for advice and information. To meet other families with disabled children, join Contact’s closed (private) Facebook group.
Also known as: Early Infantile Epileptic Encephalopathy Background Ohtahara syndrome is a rare form of childhood epilepsy, which was first described by Ohtahara in 1976. It is one of several severe epilepsy syndromes including West syndrome and Lennox-Gastaut syndrome that have been defined by the age of onset. Seizures often begin in the first ten days of life and usually before the age of three months. Boys are slightly more often affected than girls. Credits Medical text written August 2004 by Contact a Family. Approved August 2004 by Professor Brian Neville. Last updated January 2012 by Professor Brian Neville, Emeritus Professor of Paediatric Neurology, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK and Professor H Cross, The Prince of Wales’s Chair of Childhood Epilepsy, UCL Institute of Child Health, Great Ormond Street Hospital for Children and Young Epilepsy, UK. What are the symptoms? The signs of Ohtahara syndrome are: tonic seizures (stiffening of limbs) psychomotor development delay (delay in development of mental and motor skills) there may development of other neurological difficulties such as: diplegia (paralysis of like parts on either side of the body) hemiplegia (paralysis/weakness of one side of the body) tetraplegia (spasticity and weakness of all four limbs) ataxia (a lack of balance and coordination) dystonia (abnormal movements with increased tone). What are the causes? Ohtahara syndrome is most often caused by a developmental abnormality of the brain (also known as a cerebral malformation). The condition occasionally occurs as a result of glycine encephalopathy or other metabolic disorders (see entry Inherited Metabolic diseases). Genetic causes have also recently been reported. It is therefore not a single disease; it is a type of epilepsy with many different causes. How is it diagnosed? Ohtahara syndrome is diagnosed by age of onset and type of seizures, and confirmed by an electroencephalogram (EEG), which records the electrical activity of the brain. Children with Ohtahara syndrome show a particular type of electrical activity that alternates between showing spikes and suppression of activity known as ‘suppression-burst’. How is it treated? There is no cure for Ohtahara syndrome. Treatment helps to reduce the symptoms a child experiences. Control of the seizures is often difficult and the balance of the advantages (extending the times between seizures) and disadvantages (sleepiness, weight gain) of using anticonvulsant drugs such as phenobarbitone needs to be considered. Use of anticonvulsant drugs will not halt the deterioration in psychomotor development. If there is a clear structural brain abnormality on one side causing Ohtahara syndrome then a child should undergo evaluation as to whether this can be removed by surgery, with a chance of resolving or improving seizures. Children with Ohtahara syndrome often have severe developmental delay and so usually remain totally dependent on others. Sadly, children often die within the first two years of life. Those children that survive beyond two years of life remain severely disabled. Inheritance patterns and prenatal diagnosis Inheritance patternsOften the exact cause Ohtahara syndrome is unknown and can include cerebral malformations, metabolic and direct genetic disorders. All may occur because of genetic predisposition and therefore have a risk of recurrence. Advice from a geneticist should be sought. Prenatal diagnosisPrenatal diagnosis may be possible if the type of Ohtahara syndrome is identified as being caused by a genetic disorder. Is there support? There is no support group for Ohtahara syndrome in the UK. General support can be obtained from epilepsy support organisations (see entry Epilepsy). Families can use Contact’s freephone helpline for advice and information To meet other families with disabled children, join Contact’s closed (private) Facebook group.
What are the symptoms? The signs of Ohtahara syndrome are: tonic seizures (stiffening of limbs) psychomotor development delay (delay in development of mental and motor skills) there may development of other neurological difficulties such as: diplegia (paralysis of like parts on either side of the body) hemiplegia (paralysis/weakness of one side of the body) tetraplegia (spasticity and weakness of all four limbs) ataxia (a lack of balance and coordination) dystonia (abnormal movements with increased tone). What are the causes? Ohtahara syndrome is most often caused by a developmental abnormality of the brain (also known as a cerebral malformation). The condition occasionally occurs as a result of glycine encephalopathy or other metabolic disorders (see entry Inherited Metabolic diseases). Genetic causes have also recently been reported. It is therefore not a single disease; it is a type of epilepsy with many different causes. How is it diagnosed? Ohtahara syndrome is diagnosed by age of onset and type of seizures, and confirmed by an electroencephalogram (EEG), which records the electrical activity of the brain. Children with Ohtahara syndrome show a particular type of electrical activity that alternates between showing spikes and suppression of activity known as ‘suppression-burst’. How is it treated? There is no cure for Ohtahara syndrome. Treatment helps to reduce the symptoms a child experiences. Control of the seizures is often difficult and the balance of the advantages (extending the times between seizures) and disadvantages (sleepiness, weight gain) of using anticonvulsant drugs such as phenobarbitone needs to be considered. Use of anticonvulsant drugs will not halt the deterioration in psychomotor development. If there is a clear structural brain abnormality on one side causing Ohtahara syndrome then a child should undergo evaluation as to whether this can be removed by surgery, with a chance of resolving or improving seizures. Children with Ohtahara syndrome often have severe developmental delay and so usually remain totally dependent on others. Sadly, children often die within the first two years of life. Those children that survive beyond two years of life remain severely disabled. Inheritance patterns and prenatal diagnosis Inheritance patternsOften the exact cause Ohtahara syndrome is unknown and can include cerebral malformations, metabolic and direct genetic disorders. All may occur because of genetic predisposition and therefore have a risk of recurrence. Advice from a geneticist should be sought. Prenatal diagnosisPrenatal diagnosis may be possible if the type of Ohtahara syndrome is identified as being caused by a genetic disorder. Is there support? There is no support group for Ohtahara syndrome in the UK. General support can be obtained from epilepsy support organisations (see entry Epilepsy). Families can use Contact’s freephone helpline for advice and information To meet other families with disabled children, join Contact’s closed (private) Facebook group.
What are the symptoms? The signs of Ohtahara syndrome are: tonic seizures (stiffening of limbs) psychomotor development delay (delay in development of mental and motor skills) there may development of other neurological difficulties such as: diplegia (paralysis of like parts on either side of the body) hemiplegia (paralysis/weakness of one side of the body) tetraplegia (spasticity and weakness of all four limbs) ataxia (a lack of balance and coordination) dystonia (abnormal movements with increased tone).
What are the causes? Ohtahara syndrome is most often caused by a developmental abnormality of the brain (also known as a cerebral malformation). The condition occasionally occurs as a result of glycine encephalopathy or other metabolic disorders (see entry Inherited Metabolic diseases). Genetic causes have also recently been reported. It is therefore not a single disease; it is a type of epilepsy with many different causes.
How is it diagnosed? Ohtahara syndrome is diagnosed by age of onset and type of seizures, and confirmed by an electroencephalogram (EEG), which records the electrical activity of the brain. Children with Ohtahara syndrome show a particular type of electrical activity that alternates between showing spikes and suppression of activity known as ‘suppression-burst’.
How is it treated? There is no cure for Ohtahara syndrome. Treatment helps to reduce the symptoms a child experiences. Control of the seizures is often difficult and the balance of the advantages (extending the times between seizures) and disadvantages (sleepiness, weight gain) of using anticonvulsant drugs such as phenobarbitone needs to be considered. Use of anticonvulsant drugs will not halt the deterioration in psychomotor development. If there is a clear structural brain abnormality on one side causing Ohtahara syndrome then a child should undergo evaluation as to whether this can be removed by surgery, with a chance of resolving or improving seizures. Children with Ohtahara syndrome often have severe developmental delay and so usually remain totally dependent on others. Sadly, children often die within the first two years of life. Those children that survive beyond two years of life remain severely disabled.
Inheritance patterns and prenatal diagnosis Inheritance patternsOften the exact cause Ohtahara syndrome is unknown and can include cerebral malformations, metabolic and direct genetic disorders. All may occur because of genetic predisposition and therefore have a risk of recurrence. Advice from a geneticist should be sought. Prenatal diagnosisPrenatal diagnosis may be possible if the type of Ohtahara syndrome is identified as being caused by a genetic disorder.
Is there support? There is no support group for Ohtahara syndrome in the UK. General support can be obtained from epilepsy support organisations (see entry Epilepsy). Families can use Contact’s freephone helpline for advice and information To meet other families with disabled children, join Contact’s closed (private) Facebook group.
If your child is affected by a medical condition or disability we can help. Call our freephone helpline on 0808 808 3555 to get information, support and advice. You can also browse our range of parent guides on aspects of caring for a disabled child in our resource library. To meet other parents see support groups below or meet other parents online in our closed Facebook group Please see below for reliable medical information on Obsessive Compulsive disorder produced by alternative providers. NHS websitewww.nhs.uk/conditions Although alternative links have been selected with great care, Contact cannot accept responsibility for any inaccuracies or errors. Alternative information providers give details of their quality control procedures on their website, which includes review of information by a qualified medical professional. Is there support? OCD Action Helpline: 0300 636 5478Email: [email protected]Website: ocdaction.org.uk OCD Action is a Registered Charity in England and Wales No. 1154202. It provides information and support to anyone affected by Obsessive Compulsive Disorder, and runs support groups across the UK. Group details last reviewed June 2024.
Is there support? OCD Action Helpline: 0300 636 5478Email: [email protected]Website: ocdaction.org.uk OCD Action is a Registered Charity in England and Wales No. 1154202. It provides information and support to anyone affected by Obsessive Compulsive Disorder, and runs support groups across the UK. Group details last reviewed June 2024.
Is there support? OCD Action Helpline: 0300 636 5478Email: [email protected]Website: ocdaction.org.uk OCD Action is a Registered Charity in England and Wales No. 1154202. It provides information and support to anyone affected by Obsessive Compulsive Disorder, and runs support groups across the UK. Group details last reviewed June 2024.
Brittle bone disease or osteogenesis imperfecta (OI) is a genetic condition that causes abnormality in collagen protein that the body needs for bones as well as other structures such as skin, ligaments and teeth. Seven forms of OI have been described. They include mild, moderate and severe forms. In this article What are the symptoms of osteogenesis imperfecta? All people with OI have weak bones, which makes them susceptible to fractures. People with OI are usually below average height (short stature). However, the severity of the disease varies greatly. The classic symptoms include: blue tint to the whites of the eyes (blue sclera) multiple bone fractures – the frequency of fractures may increase in adolescence early hearing loss (deafness). Because collagen is also found in ligaments, people with OI often have loose joints (hypermobility) and flat feet. Some types of OI also lead to the development of poor teeth. Symptoms of more severe forms of OI may include: bowed legs and arms kyphosis (over-curvature of the upper back) scoliosis. What are the causes of brittle bones? OI is a genetic disorder. Most cases (90 percent) involve a change (mutation) in type 1 collagen – the protein ‘scaffolding’ of bone and other connective tissues. Other cases of OI are caused by changes in other genes in bone development. How is osteogenesis imperfecta diagnosed? OI is usually suspected in children whose bones break with very little force. A physical examination may show that the whites of their eyes have a blue tint. A definitive diagnosis may be made on the basis of examination of the person, examining the skeleton by X-rays, excluding other causes of bone fragility and sometimes by genetic tests. How is osteogenesis imperfecta treated? Fractures need to be treated, but the immobilisation period should be kept to a minimum as activity allows muscles and bones to stay as strong as possible. It is important for someone with OI to have a well-balanced diet with adequate calcium. There is no specific drug therapy for OI, but it has been shown that a group of drugs called bisphosphonates can reduce bone loss, the number of fractures and the chronic pain experienced by these children. Most children obtain maximum benefit from this drug over the first two years of treatment. Some children may benefit from insertion of rods to support the bones. Regular monitoring of other functions such as hearing is required. Inheritance patterns and prenatal diagnosis Inheritance patternsType I and IV are usually inherited in an autosomal dominant manner but new mutations in a family (sporadic) often occur. Affected families should be referred to a genetics centre for information and support. Prenatal diagnosisSevere cases may be detected by ultrasound scanning. A DNA test may be available at eight weeks for some affected families where the genetic mutation is already known. Support for children with OS and their families If your child is affected by a medical condition or disability, we can help. Call our freephone helpline on 0808 808 3555 to get information, support and advice. We also offer emotional support for parents via our Listening Ear service. We have a range of parent guides on aspects of caring for a disabled child in our resource library. You may also find our Early Years Support useful, which contains links to parent carer workshops and help for families going through the diagnosis process. We’ve listed a support group for osteogenesis imperfecta below and you can also meet other parents online in our closed Facebook group. Brittle Bone Society Tel: 01382 204 446Email: [email protected]Website: brittlebone.org The Society is a Registered Charity in England and Wales No. 272100 and Scotland No. SC010951. It provides information and support to people affected by the bone condition Osteogenesis Imperfecta in the UK and Republic of Ireland. Group details last updated December 2020. Credits Medical text written November 2002 by Professor SF Ahmed. Last updated December 2012 by Professor SF Ahmed, Consultant in Paediatric Endocrinology and Bone Metabolism, Royal Hospital For Sick Children, Yorkhill, Glasgow, UK.
Also known as: Ohdo Blepharophimosis Ohdo and his colleagues from Japan first described two sisters and a cousin with learning disabilities (see entry Learning Disability) associated with congenital heart disease, blepharophimosis (small eye openings), blepharoptosis (drooping eyelids) and small teeth. Following this report, doctors from various countries have described children with similar problems. Currently, the term Ohdo syndrome is reserved for those individuals who have similarities to the patients reported by Say, Barber and Biesecker (SBB type) and in fact the original Ohdo patients may have had a different condition. The condition called Young-Simpson syndrome is so similar to the SBB type of Ohdo syndrome that many doctors consider them to be the same disorder. In this article What are the symptoms of OHDO syndrome? Affected children are usually very floppy at birth and have major feeding problems requiring tube feeding. They have generally decreased movements, particularly facial movements. Some, but not all, children have heart problems and some have an absent midline structure of the brain (absent corpus callosum; see entry Agenesis of the Corpus Callosum). When the teeth erupt they are often very small. Many older children have joint problems ranging from mild bending of the fingers to more severe hip disorders and problems with dislocation of the kneecap. Progress in the first year of life is slow, and head control, sitting and walking occur late but ultimately, progress is often better than was anticipated at first. All children have mild-to-moderate learning difficulties (see entry Learning Disability). Thyroid problems (underactive or overactive) appear to occur with an increased incidence in Ohdo syndrome (see entry Thyroid disorders). What are the causes of OHDO syndrome? The cause of Ohdo syndrome remains unknown and research is ongoing. A genetic cause is suspected. How is OHDO syndrome diagnosed? The diagnosis of Ohdo syndrome remains a clinical one and is usually made by a clinical geneticist on the basis of the physical features, after exclusion of other causes. There are some other syndromes associated with blepharophimosis which have features that overlap with Ohdo syndrome SBB type and these include blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). There is no specific test for Ohdo syndrome as yet. How is OHDO syndrome treated? There is no specific cure or treatment for Ohdo syndrome but a number of therapies may help at different stages of life. These include physiotherapy, occupational therapy and a detailed assessment of special educational needs. There should be regular review by a paediatrician and thyroid function should be checked every one to two years, or if symptoms develop. Inheritance patterns and prenatal diagnosis Inheritance patternsMost individuals with the typical signs of the SBB type of Ohdo syndrome have been the only affected child in their family other than one possible case of a parent-to-child transmission. Genetic counselling is recommended for families, however, so that other conditions can be ruled out. There is no specific prenatal diagnostic test for Ohdo syndrome. Prenatal diagnosisRecurrence risk seems to be very low. The risk for the offspring of affected individuals may be higher, approaching 50 per cent. Detailed ultrasound scanning in subsequent pregnancies, looking particularly for heart and brain defects and for hydramnios (an excessive amount of the fluid that the baby floats in whilst in the womb) due to impaired swallowing, may be offered. Is there support for people affected by OHDO syndrome and their families? If your child is affected by a medical condition or disability, we can help. Call our freephone helpline on 0808 808 3555 to get information, support and advice. We also offer emotional support for parents via our Listening Ear service. We have a range of parent guides on aspects of caring for a disabled child in our resource library. You may also find our Early Years Support useful, which contains links to parent carer workshops and help for families going through the diagnosis process. We’ve listed some support groups below and you can also meet other parents online in our closed Facebook group. Ohdo Syndrome Family Network Tel: 01614 288583Email: [email protected] The Network was established in 1997. It offers support and information and links families where possible. The Network is in touch with over 60 families, has a presence on Facebook. Group details last updated January 2013. Credits Medical written January 2003 by Professor Dian Donnai, Consultant Clinical Geneticist, St Mary’s Hospital, Manchester, UK. Last updated October 2010 by Professor J Clayton-Smith, Consultant Clinical Geneticist, Genetic Medicine, St Mary’s Hospital, Manchester, UK.