Condition AZ: c

Symptoms in small babies include hypotonia (floppiness) and low muscle tone. As the muscles are weak and immobile, contractures (tightness) in the hip, ankle, knee and elbow joints are common. In children that do not have contractures, initial problems may be difficulties holding the head, and delays in sitting and walking.

Some forms of CMDs can have associated brain changes on a magnetic resonance imaging (MRI) scan. The pattern of these brain MRI changes helps to identify the subtype of CMD. Some, but not all children with CMD and brain changes visible on an MRI scan, may have learning difficulties (see entry Learning Disability) with or without epileptic seizures (see entry Epilepsy). Learning difficulties can be mild, moderate or severe and do not get worse over time.

Approximately 40 per cent of children with CMD have a mutation in the LAMA2 gene, which is responsible for producing the protein merosin. At least 13 causative genes have been implicated in CMD, each of them resulting in specific symptoms for a patient. A number of people with CMD don’t have mutations in any of the genes already described.

A high level of the enzyme creatine kinase (CK) can indicate the condition. Electromyography (measuring the electrical activity of muscle) may be undertaken to establish how well the muscles are working, but is not essential. Muscle imaging, usually with ultrasound, and muscle biopsy are used to identify the exact type of CMD. MRI scans of the brain can help to diagnose particular subtypes of CMD that cause changes in the brain. In types of CMD where the genetic defect is known, genetic testing offers a definitive diagnosis.

There is no cure for CMD. A programme of physiotherapy and exercises should be devised soon after diagnosis to improve muscle function and mobility. If there are problems with breathing at night, an overnight breathing study maybe needed to monitor breathing quality and a ventilator may be used to assist breathing. Flu jabs and other vaccinations are advisable in some children to prevent the occurrence of chest infections.

Inheritance patterns
CMDs are transmitted in an autosomal recessive manner in most instances, although sporadic cases have been documented.

Prenatal diagnosis
This is possible via amniocentesis after 15 weeks of pregnancy or chorionic villus sampling between 10 and 13 weeks of pregnancy if the genetic defect causing the subtype of CMD in a family is known.

Muscular Dystrophy UK

Helpline: 0800 652 6352
Email: [email protected]
Website: musculardystrophyuk.org

The Charity is a Registered Charity in England and Wales No. 205395, and Scotland No. SC039445. It provides information and support for anyone affected by muscular dystrophy and other muscle-wasting conditions. Muscular Dystrophy UK also provide grants towards the cost of specialist equipment.

Group details last updated September 2017.

CMNs show a number of features, including:

• variation in size
• colour of the CMN is often uneven and can vary over the years
• texture: the texture of large CMNs is softer, looser and more wrinkled than normal skin
• hairiness: CMNs are usually hairier than normal areas of skin
• lumpiness: in large CMNs, quite often there are raised or lumpy areas
• eczema: the skin overlying a CMN is often rather dry and itchy, and may sometimes develop eczema
• underlying absence of fat: the presence of many melanocytes interferes with the development of the layer of fat that is normally present between the skin and underlying muscle and bone.

CMN can also be associated with other problems if they are large or multiple:

• brain or spine problems – these can usually be detected using MRI scans, ideally in the first 6 months of life. This can be called neurocutaneous melanosis, or CMN syndrome
• a risk of melanoma (a type of skin cancer). This is rare overall, but higher in patients with very large or multiple naevi.

Birthmarks are the visible effect of changes that have occurred during a child’s development before birth. CMN are caused by a genetic mutation that occurs during development in the womb. When there are very large or multiple CMN, or problems with the brain, this is caused by a mutation occurring very early in development. This mutation has a very low chance of occurring again in the same family, and is not passed on to future generations. In other words it only causes CMN in one person.

CMN are diagnosed clinically – in other words by a specialist doctor looking at the birthmark(s). The associated problems in the brain need a magnetic resonance imaging (MRI) scan to be diagnosed.

Most often no treatment is required. If the CMN is somewhere very visible, such as a large one on the face, then surgery may be available to remove it. This should be discussed with a paediatric dermatologist (children’s skin specialist).

Inheritance patterns
CMNs are chance events and there is very little risk for further children

Prenatal diagnosis
It is very unlikely that the presence of a CMN could be identified by ultrasound scanning or any other method. Occasionally something is seen on the skin but not diagnosed as they are rare.

Caring Matters Now

Tel: 07786 458 883
Email:  [email protected]
Website: caringmattersnow.co.uk

Caring Matters Now is a Registered Charity in England and Wales No. 1120988. It provides information and support for people with Congenital Melanocytic Naevus (CMN) and their families. 

Group details last updated December 2014.

Information and support in the UK for congenital melanocytic naevi is also provided by the Birthmark Support Group (see entry Vascular Birthmarks).

There are only two features of this condition: a totally inability to feel any pain ever; and no sense of smell. Otherwise, the affected individuals are healthy, of normal intelligence and have no other problems with their nervous system. The condition is inherited in an autosomal recessive manner and is caused by having a change (mutation) in each SCN9A gene. SCN9A seems to be an ‘amplifier’ for all the specific pain receptors, and if not present, means a pain nerve can’t be fired. The only way to make a diagnosis is by analysing the SCN9A gene to look for the mutation. The management of children with this condition can be challenging and involves stopping them injuring themselves, teaching them what is dangerous, and when to get medical attention. An informed and involved GP, paediatrician and orthopaedic surgeon are an absolute necessity, especially in the first ten years of life.

Inheritance pattern
Autosomal recessive.

Prenatal diagnosis
This is available in affected families.

This is the name of a group of disorders which have in common a failure of development of the pain sensing nerves. They are best called the hereditary and sensory autonomic neuropathies (HSANs), and there are five separate conditions. The various categories are distinguished according to features, including age of onset, progressive (becoming worse over time) or non-progressive, presence or absence of abnormalities of the autonomic nervous system if the system is sympathetic or parasympathetic and also according to the nature of structural abnormalities in peripheral nerves.

HSAN type I occurs in late childhood or more commonly adolescence. The nerve fibres involved in pain sensation and their connections to the spinal cord decline in function. Impaired pain sensation starts furthest away from the spinal cord in the legs and later the arms. Nerve biopsy (removal of a small piece of nerve tissue for examination) shows that the nerves involved in sensing and movement are degenerated. A mutation in the SPTLC1 gene on chromosome 9 is responsible for HSAN type I. Often there is a dull continuous pain initially which gradually disappears as all pain sensing is lost. Due to the unawareness of pain, damage to skin, nails, and joints occurs without the affected person being aware until they see the bruise, skin infection, or see the deformity at a site of fracture. The condition is usually diagnosed and managed by adult neurologists (specialist doctor in neurology).

Inheritance pattern
Autosomal dominant.

Prenatal diagnosis
This is potentially possible.

HSAN2 is congenital (present at birth) or occurs very early on in life. There is universal absence of pain in most, and reduced ability to feel anything from touch (tactile sensation) in many, resulting in burns, mutilation of finger tips, painless fractures and painless arthritis with joint destruction. Usually there are areas of normal sensation on the body. There may be impaired bladder sensation with overdistention (enlargement of the bladder). There is deafness in some affected individuals. In most, the condition does not progress, or progresses very slowly. Rarely there is rapid progression. Despite the name, affects on the autonomic nervous system are absent or minimal. A sensory nerve biopsy shows a marked reduction in the number of myelinated nerves and degeneration of those myelinated nerves, and a lesser loss of non-myelinated nerves. Myelin is a special covering around nerves which insulates them and allows nerve impulses to be effectively passed through the nerve. A mutation in the WNK1 gene causes the condition and analysis of this gene may confirm the diagnosis.

Inheritance pattern
Autosomal dominant

Prenatal diagnosis
This is potentially possible.

This genetic condition is more commonly known as Riley-Day syndrome or Familial Dysautonomia. It occurs almost exclusively in Ashkenazi Jews. It is present at birth and symptoms include floppiness, severe feeding difficulties (vomiting, constipation), pneumonia (that occurs because of an inability to swallow and cough), lack of taste, inability to produce tears, unstable temperature and blood pressure control. The condition is cause by a progressive degeneration of sensory, sympathetic, and parasympathetic neurons throughout life. There is indifference to pain, but this is usually far less of a problem than the autonomic dysfunction. Intelligence is usually normal, but emotions can be unstable. Sadly, life expectancy is severely reduced with pneumonia is a common cause of death in childhood. In adulthood there may be renal (kidney) failure. Treatment is complex, will involve a specialist and life-long. Testing for the condition can be carried out by looking for the mutation in the IKBKAP gene.

Inheritance pattern
The condition is inherited in an autosomal recessive

Prenatal diagnosis
This is possible if the genetic mutation in a family is known.

HSAN4 and HSAN5 are the same condition with different severities (which had originally suggested that they may be different conditions). HSAN4 was known as congenital insensitivity to pain and anhidrosis (inability to sweat), but this can lead to confusion with CIP. HSAN4/5 is present at birth with a lack of pain sensing, inability to feel and regulate temperature. In the first few years, the lack of sweating and dry skin lead to intense itching, and inability to sense temperature means that hyperthermia (leading to fits and exhaustion) is a risk. Nearly all affected individuals have mild-moderate learning difficulties, and many self-injure, which can be distressing. Children affected are at risk of Staphylococcal infections such as osteomyelitis and septic arthritis, as well other skin infections. An immunologist should be involved in providing care to the child. Nerve biopsy shows a lack of unmyelinated sensory nerves. Diagnosis is possible by looking for mutation in NTRK1 and NGF genes, which cause the condition.

Inheritance pattern
The condition is inherited in autosomal recessive manner.

Prenatal diagnosis
This is possible if the genetic mutation in a family is known.

There is no support group for congenital insensitivity/indifference to pain. Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families. You can also connect with other families in our closed Facebook group

Information and support in the UK for familial dysautonomia (HSAN Type III) is provided by the Dysautonomia Society of Great Britain (see entry Familial Dysautonomia).

Information and support in the UK for Riley-Day syndrome (HSAN Type III) is provided by Climb (see entry Inherited Metabolic Diseases).

If the hypoglycaemia is not treated it can cause brain damage, learning disability and, in severe cases, death. Neonatal onset CHI shows in the first days or weeks after birth and is the most severe form. Infant onset CHI shows in the first few months, or even years, of life and is milder.

Features of neonatal onset CHI:

• hunger
• lethargy (drowsy/tired)
• seizures
• apnoea (suspension of breathing)
• agitation/restlessness
• pallor (looking pale)
• poor feeding
• irritability
• sweating.

Features of infant onset CH include:

• any of the above symptoms
• confusion
• mood or behaviour changes.

Overproduction of insulin by the beta cells in the pancreas is the cause of CHI. It is due to a genetic change that means that the amount of insulin produced is not regulated. Insulin removes excess sugars from the blood and converts it into glycogen. A number of gene mutations (changes to DNA) are now known to be involved in CHI. So far, mutations in the following genes have been identified: ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, HNF4A/1A and UCP2. However, in about 50 per cent of patients the genetic basis of the disease is not known.

Fast diagnosis of CHI can be made if blood and urine samples are taken while in an episode of hypoglycaemia. Following diagnosis, children should be referred to a specialist centre.

Treatment of CHI in the short term is by immediate correction of the hypoglycaemia by intravenous glucose to prevent further hypoglycaemia and brain damage. In the longer term, other medications, such as diazoxide, are used. A pancreatectomy (surgery to remove a large or small part of the pancreas) has to be carried out when medication does not maintain proper regulation of the production of insulin.

Inheritance patterns
Autosomal recessive inheritance in the most common form of severe inherited CHI. However, autosomal dominant forms have now also been described. Genetic counselling should be sought in families known to be at risk of CHI.

Prenatal diagnosis
In some forms of CHI, amniocentesis at 15 to 18 weeks of pregnancy may be possible where there is already an affected family member and the mutation causing CHI has been identified. However, this is not possible in all forms of CHI.

Children’s Hyperinsulinism Charity

Email: [email protected]
Website: hyperinsulinism.co.uk

The group is a Registered Charity No. 1165562. They are a UK charity to support families who have children with Congenital Hyperinsulinism by holding conferences, raising awareness and funds for research.

Group details last updated July 2016.

PMM-CDG
People affected may have:

• neurological problems such as developmental delay (see entry Global Developmental Delay)
• visual problems such as squint or retinitis pigmentosa
• cerebellar hypoplasia (underdevelopment of the cerebellum in the brain)
• liver disease
• kidney cysts
• heart abnormalities
• diarrhoea
• abnormal fat distribution under the skin
• patients often have inverted nipples.

A similar range of problems are seen in most other forms of CDG. An exception is PMI-CDG, previously called CDG-Ib.

PMI-CDG
People affected may have liver disease, diarrhoea and severe failure to thrive. They may have low blood sugar levels due to too much insulin, but they do not have neurological problems.

In all forms of CDG, there is a problem making glycoproteins. Glycoproteins have several important functions, including signalling how cells in the body interact with one another, assisting the transfer of nutrients around the body, having a role in the coagulation of blood and acting as hormones in regulating certain activities or organs in the body. A number of enzymes are involved in attaching sugars to glycoproteins. In each type of CDG, a different one of these enzymes is faulty, due to a genetic change (mutation).

Most forms of CDG can be screened for by electrophoresis of transferrin, a glycoprotein present in blood. Electrophoresis is a method that sorts molecules according to their size and charge – by doing this, scientists can see if there is any change to the sugar chain, which indicates CDG. Those results are then followed up by enzyme and/or genetic testing to identify the distinct CDG subtype.

Although there is no cure for the different CDG types, lots can be offered to the patient.

PMM-CDG
Treatment aims to provide relief for any symptoms and support in the care of the individual. Feeding might be helped with a tube. A wide range of specialists may need to be consulted; these may include paediatricians, neurologists, ophthalmologists, orthopaedic specialists (skeletal), physiotherapist, speech therapists and the aid of a dietician may also be useful.

PMI-CDG
This is the only CDG that has an effective treatment. Individuals are given a specific sugar called mannose, which then can improve the glycosylation. This treatment has been successful in several cases of PMI-CDG.

The support group CLIMB have information on file for the rarer types of CDG. Please contact them for more information.

Inheritance patterns
All forms of CDG show an autosomal recessive pattern of inheritance. Affected families should be referred to a genetics centre for information and support.

Prenatal diagnosis
This can be offered if the genetic background (mutation) in a family is already known.

Information and support in the UK for congenital disorders of glycosylation is provided by Climb (see entry Inherited Metabolic diseases).

The main symptom is the person’s inability to breathe deeply enough, leading to a need for assisted ventilation, most commonly beginning shortly after birth. Affected individuals also do not feel breathlessness and so under-breathe during feeding, exercise or when concentrating. The condition ranges in severity with the worst affected under-breathing both during sleep and when awake. Those least affected may not present till older and may be mildly affected during sleep and with normal breathing when awake.

Children with CCHS may have other problems related to the body’s automatic nervous system, including:

• Hirschsprung’s disease – a failure of the bowel to move normally
• swallowing difficulties
• heart rhythm disorders (see entry Heart Defects)
• increased risk of tumours of nerve tissue
• ‘blue-breath holding’ episodes – stopping breathing and turning blue when crying
• fainting episodes
• epileptic or absence seizures (see entry Epilepsy)
• learning difficulties (see entry Learning Disability)
• eye problems, such as squints
• unusual responses to anaesthestic
• poor temperature control.

CCHS is caused by a mutation (a change) in the PHOX2B gene. This mutation affects the development of the foetus’ autonomic nervous system, which is responsible for involuntary processes such as breathing and heart rhythm.

The diagnosis of CCHS is confirmed by the genetic mutation, but there are some cases where this is negative and the diagnosis relies on recording under-breathing from sensors that measure levels of oxygen and carbon dioxide (the body’s waste gas).

Treatment of CCHS involves providing assisted (mechanical) ventilation when the individual breathes inadequately on their own. No medication has been shown to sufficiently stimulate the breathing enough. The usual ventilator devices blow air into the lungs, through either a tracheostomy (a surgically created hole in the front of the neck), or a mask.  In cases where ventilation is needed during both the day and night, this is given through the tracheostomy or, after infancy, by surgically implanted breathing pacemakers (small devices delivering an electrical stimulus) that stimulate the nerves to the diaphragm, the main muscle involved in breathing.

Individuals with CCHS need regular monitoring of their oxygen levels with a sats monitor (pulse oximeter) and sometimes with a carbon dioxide monitor to identify inadequate ventilation. Giving additional oxygen alone would be inadequate treatment. Parents can be trained to look after a child’s ventilation at home.

As children grow, their need for ventilation may change and so regular review is required. The condition is life-long, but most children do well, attend school and have a normal life while awake. Some children need bowel surgery or heart pacemakers for associated complications.

Inheritance patterns
The mutation in the PHOX2B gene is passed to children in an autosomal dominant manner.

Prenatal diagnosis
This is possible if a PHOX2B mutation has been found in one of the parents. Samples of cells from a foetus can be collected during the pregnancy and tested for the mutation in the PHOX2B gene.

CCHS Support Group

Tel: 01423 421221
Email: via website
Website: cchssupport.co.uk

The Group provides support for families affected by Congenital Central Hypoventilation Syndrome throughout the UK. It organises conferences for families to meet up and share experiences. These events are also an opportunity to invite CCHS physicians and researchers to share their insight on research and treatments. 

Group details last updated November 2019.

CBPS patients have weakness of the face, throat, tongue and the chewing process, with lack of speech or slurred speech and drooling. Most have learning impairments (see entry Learning Disability), behaviour problems and epilepsy. Arthrogryposis (fixed deformity of the ankle joints) has been described in some patients. Seizures usually begin between the ages of four to 12 years and are poorly controlled in about 60 per cent of patients. The most frequent seizure types are atypical absences, tonic or atonic drop attacks and tonic-clonic seizures, sometimes occurring as Lennox-Gastaut syndrome. A minority of patients have partial seizures.

Consistent familial recurrence has been reported only for bilateral perisylvian polymicrogyria, which is sporadic in the great majority of patients. In some families, children with similar problems with and without MRI abnormalities have been observed. A genetic basis is also possible for unilateral polymicrogyria, at least in some cases.

Bilateral perisylvian polymicrogyria has been reported in children born from identical twin pregnancies that were complicated by twin-twin transfusion syndrome.

This is primarily an MRI diagnosis by may need careful examination to be sure if polymicrogyria are present.

Seizures are treated in the usual fashion but there are often difficulties in their management. In addition these children very commonly have cognitive delay, attention deficit hyperactive disorder, autism spectrum condition, depression and anxiety and should be screened and treated for these.

Inheritance patterns
Several families with multiple affected members have been reported with possible autosomal recessive, dominant and X-linked recessive inheritance. These families have been linked to the Xq28 chromosomal region but the causative gene is not known at present.

Prenatal diagnosis
Prenatal diagnosis using fetal ultrasound or magnetic resonance imaging may be particularly difficult as the regions of the brain that are involved in this malformation may not have reached their final folding until birth.

Information and support in the UK for congenital bilateral perisylvian syndrome is provided by the Worster-Drought Syndrome Support Group (see entry Worster-Drought syndrome).

There is no support group for congenital and acquired brain damage and dysfunction in childhood in the UK. Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families.

The symptoms of 21 hydroxylase deficiency seen in a child depends on the severity of the enzyme defect and the sex of the child. Boys with a severe defect will show symptoms at about ten days of age with vomiting, dehydration and weight loss – also known as the ‘salt-losing crisis’.

Girls with a severe defect will have ambiguous (non-feminised) genitalia at birth due to the effect of androgen over production in the developing baby. Unless treated promptly these girls will also develop a ‘salt-losing crisis’. Boys and girls with a mild defect will have symptoms later in childhood with signs of androgen excess – tall stature, enlargement of penis or clitoris, and early development of pubic hair but no salt-losing crisis.

Treatment consists of surgery in girls to reduce the size of the clitoris and open up the lower end of the vagina. Both sexes require hydrocortisone to suppress ACTH secretion and switch off androgen production, fludrocortisone to replace aldosterone and (during the first year of life) salt supplements.

The dose of hydrocortisone has to be carefully adjusted since under-treatment will result in over-production of androgen with excessive growth and virilisation (abnormal development of male sexual characteristics in a female), while over-treatment will cause slow growth and obesity.

By adjusting the dose of hydrocortisone against the child’s size, growth rate, skeletal maturity (‘bone age’) and adrenal steroid levels, the treatment can be optimised and the general health of these children is good. It is important for parents to learn how to increase the hydrocortisone dose during acute illness, so as to mimic the normal cortisol response to stress. In particular, there is a need for an emergency regimen of hydrocortisone injection and salt replacement in severe illness.

Inheritance patterns
Autosomal recessive.

Prenatal diagnosis
Once an affected child has been diagnosed, genetic testing can be carried out on the parents and patient. Diagnosis can then be done in the developing baby by chorionic villus sampling (CVS) at 9 to 10 of pregnancy.

Antenatal treatment (for the baby before birth) is available by treating the mother throughout pregnancy with dexamethasone (a strong cortisol equivalent) which will prevent the virilisation of an affected female fetus.

Information and support in the UK for congenital adrenal hyperplasia is provided by Metabolic Support UK (see entry Inherited Metabolic diseases).

Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families. You can also connect with other families in our closed Facebook group

Vision may or may not be affected depending on the part of the eye involved. Coloboma may be unilateral (on one side) or bilateral (on both sides) and if bilateral, can be quite asymmetrical. It may be an isolated ocular finding or may be associated with other eye defects, such as microphthalmia (small eye, see entry Anophthalmia) in the same or opposite eye and, extremely rarely, Anophthalmia (absent eye) in the opposite eye.

Coloboma may occur on its own (be isolated) or be associated with other problems in the baby, sometimes as part of a specific genetic disorder. Several genes, including PAX2, MAF and SHH, can be associated with isolated ocular colobomas. New genes are being continually discovered. Several genes are implicated in recognised syndromes, such as the CHD7 gene in CHARGE syndrome.

At present, there is no treatment for the coloboma. A child with coloboma will require specialist checks in hospital to assess the impact of the condition on their vision. They may need glasses to assist with their vision and to correct refractive errors (for example astimatism or long or short-sightedness). The coloboma may be associated other eye defects, such as cataract, which need treatment. Sometimes the eye with a coloboma may become ‘lazy’, this occurs when the child’s brain chooses to ignore the image either because it is out of focus or poorer quality than the image from the other eye. It is important that this is detected early, since glasses and patching might help to improve this. Children with iris coloboma may be sensitive to bright light as the pupil does not constrict properly, this can be helped by using large brimmed floppy hats or sunglasses. Cosmetic contact lenses may be considered at when the child is older to provide the appearance of a round, rather than keyhole-shaped pupil and to help with sensitivity to bright light.

Inheritance patterns
The occurrence of coloboma may be sporadic or may be inherited. The mode of inheritance may be dominant, recessive or X-linked. Genetic counselling is important as there may be a recurrence risk. It is available for familial (those that occur in families) or isolated cases of coloboma.

Prenatal diagnosis
High-resolution ultrasound is unlikely to detect eye anomalies, such as coloboma prenatally. If the gene change causing coloboma in a family is known, prenatal genetic diagnosis could be offered.

Information and support in the UK for coloboma is provided by M.A.C.S. (see entry Anophthalmia).

As young babies, feeding difficulties are common in Cohen syndrome and some infants may need nasogastric tube feeding (where food is passed into the stomach via a tube in the nose). Some babies have stridor (noisy breathing), due to a floppy windpipe.

Young children with Cohen syndrome have developmental delay. They learn to walk later than the average child and their speech takes longer to develop. All children have special educational needs, with the majority attending schools for children with moderate-to-severe learning difficulties. Children with Cohen syndrome are typically very sociable and affectionate, however, a few can have behavioural difficulties that fall within the autistic spectrum (see entry Autistic Spectrum disorders).

From around ten years, children with Cohen syndrome put on more weight, especially around their tummies. However, they do not usually become generally obese. Many are short for their age and have microcephaly. Individuals with Cohen syndrome have loose, flexible joints and hypotonia (low muscle tone), which can result in difficulties with balance and coordination.

Children with Cohen syndrome often have a high roof to their mouth with overcrowding of their teeth. A specific feature of Cohen syndrome is a low number of white blood cells, called neutrophils, used by the body to fend off bacterial infections. Dental and skin infections may occur a little more frequently in some people with Cohen syndrome, however, it is rare to suffer from severe infections. Autoimmune disorders, in particular diabetes (see entry Diabetes Mellitus), thyroid disorders and coeliac disease, have been reported in some individuals.

Visual problems affect nearly all children with Cohen syndrome. These start during the preschool years with myopia (short-sightedness), which becomes more severe throughout childhood. In addition, the area at the back of the eye, known as the retina, gradually reduces in function causing poor vision in dim light and loss of the outer ranges of the visual field (known as a retinal dystrophy). Older children and adults with Cohen syndrome find it particularly difficult to see in reduced light or at night time and have ‘tunnel vision’. Their visual acuity (close vision), however, usually remains quite good. By adult life, many people with Cohen syndrome are registered partially-sighted or blind.

Adults with Cohen syndrome usually continue to live at home or in residential care as their level of independence is limited. They are usually friendly people who enjoy socialising and group activities. They remain healthy and do not have a shortened lifespan.

Cohen syndrome is caused by mutations in VPS13B also known as COH1. This gene lies on chromosome 8.

There is no ‘cure’ for Cohen syndrome. Support for visual dysfunction should include the use of low-vision aids and regular ophthalmic follow-up. Early intervention and physical, occupational and speech therapy can help address developmental delay, flexible joints and hypotonia. Granulocyte-colony stimulating factor (G-CSF) may be considered for treating neutropenia in patients who have recurrent, severe infections.

Dental and skin infections are managed in the normal way. Overcrowding of teeth, may result in some teeth being removed.

Inheritance patterns
Cohen syndrome is an autosomal recessive condition. It is caused by a double dose of a change in the Cohen syndrome gene. Both parents of an affected child with Cohen syndrome will carry one copy of the altered gene but also have a normal copy, so they are not affected. Each time they have a baby, there is a 25 per cent chance of having an affected child.

Prenatal diagnosis
Currently a gene test is not available in the UK. Prenatal diagnosis by chorionic villous sampling is possible in those families where the gene changes have already been identified, through research or non-UK laboratories.

Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families. You can also connect with other families in our closed Facebook group

CLS is characterised by a number of features some of which, to a greater or lesser degree of severity, are present in affected individuals, with females likely to be less severely affected. Manifestations include:

• significant learning delay (see entry Learning Disability)
• mild-to-moderate restricted growth (see entry Restricted Growth)
• speech problems (see entry Speech and Language Impairment)
• facial features that may include abnormally prominent brow, unusually thick eyebrows, down slanting palpebral fissures (eyelid folds), hypertelorism (widely-spaced eyes), a broad nose, protruding (nares) nostrils, maxillary hypoplasia (an underdeveloped upper jaw bone) and large ears
• progressive coarsening of the facial features
• ‘puffy’ hands and feet with tapering digits
• kyphoscoliosis (backward and lateral curvature of the spine; see entry Scoliosis)
• stimulus-induced drop attacks (episodes of interruption to the cerebral (brain) blood flow affecting the balance and causing the individual to fall) affecting ten to 20 per cent of children and adolescents.

Although no clear pattern of behavioural or psychological features relating to CLS has been established, people with the syndrome seem to have a higher incidence of psychiatric difficulties.

CLS is caused by a defective gene, RSK2, on the X chromosome (Xp22.2-p22.1). It is not clear how mutations (changes) in the DNA structure of the gene lead to the manifestations of the disorder.

How is it diagnosed?

CLS is diagnosed when Learning Disability is observed together with characteristic craniofacial and hand abnormalities. Some affected individuals have unusual brief collapses or ‘drop attacks’ that may be precipitated by emotional or auditory stimuli, for example, sudden loud noises. Molecular genetic testing of the RSK2 gene can confirm the diagnosis. However, mutations are not found in all cases. Sometimes changes in the RSK2 gene causes learning difficulties without any outward, physical signs of CLS.

Treatment of CLS is symptomatic (designed to treat the displayed symptoms in an individual), including physiotherapy and speech therapy to improve the affected individual’s abilities. The drop attacks may get better with medication prescribed by a neurologist who is aware of this complication of CLS.

Inheritance patterns
CLS is X-linked dominant. Carrier females are at risk of some learning disability and the physical features of the syndrome.

Prenatal diagnosis
This is possible where it is already known that there is an affected family member in whom a mutation has been identified. Alternatively, linkage analysis (a technique that traces patterns of heredity in at risk families, in an attempt to locate a disease-causing gene mutation by identifying traits that are co-inherited with it) can be used.

Information and support in the UK for Coffin-Lowry syndrome is provided by Metabolic Support UK (see entry Inherited Metabolic diseases).

Symptoms may occur at any age and may include weight loss, vomiting and diarrhoea. Many patients, however, may have mild, long-standing, non-gastrointestinal symptoms such as tiredness, lethargy and breathlessness. A baby predisposed to coeliac disease could, after the introduction of gluten-containing solids, develop pale, bulky, offensive smelling stools, and become miserable, lethargic and generally fail to thrive. Most children with the disease will have mild non-gastrointestinal symptoms, as in adults.

The condition is diagnosed by means of an endoscopic small intestinal biopsy, where the mucosal lining of the small intestine is seen to be damaged by inflammation, presumed to be a result of a reaction to the gluten in the diet. There is now an accurate blood test available for screening, but the diagnosis should still be confirmed by an endoscopic biopsy.

Coeliac disease is treated with a gluten-free diet, which allows the mucosal lining to heal and return towards normal. Screening suggests that the prevalence of the disease in the general population may be as high as 1 in 100, but many cases often go undiagnosed so that the number of diagnosed cases is approximately 1 in 800.

Inheritance patterns
Coeliac disease, though not inherited directly, does tend to run in families, there being a 1 in 10 chance of having an affected relative.

Prenatal diagnosis
None.

Coeliac UK

Helpline: 0333 332 2033
Email: via website
Website: coeliac.org.uk

The Organisation is a Registered Charity in England and Wales No. 1048167. It provides information and support to people in the UK with coeliac disease and dermatitis herpetiformis. 

Group details last reviewed November 2024.

Those with Cockayne syndrome may have the following symptoms:

• the face shows progressive ageing with thinning of the skin, deep sunken eyes, hair loss and dental decay
• loss of motor skills (these allow people to coordinate the movement of parts of their body)
• loss of intellectual skills. If a magnetic resonance imaging (MRI) brain scan is carried out this is apparent by changes in the white matter of the brain (known as leukodystrophy)
• deafness
• development of visual problems due to retinitis pigmentosa
• bones show thinning, the back becomes curved and there will be joint contractures (stiffness of the joint that prevents its full extension)
• sensitivity to the sun leading to blistering and excessive reddening of the skin. This has led to the recognition that in Cockayne syndrome ultra-violet (UV) light can cause damage to a person’s DNA.

The underlying cause is known to be a defect in the enzymes that repair DNA after UV damage.

There are two different enzymes (ERCC6 and ERCC8) causing the genetic defect. Diagnosis of the specific enzyme involved requires analysis of the patient’s fibroblasts (a type of skin cell), a small amount of which are removed in a harmless process called a biopsy. This analysis is carried out in highly-specialised laboratories.

A patient’s sun sensitivity can be reduced by avoiding exposure to UV light and the use of sun-block creams. However, there is no treatment for the progressive neurological degeneration.

Inheritance patterns
The disorder is inherited as an autosomal recessive trait. Clinical features are likely to be similar for affected children within the family but there may be considerable variation in the severity of this disorder between different families.

Prenatal diagnosis
This is available after the skin biopsy studies have been completed and the enzyme deficiency causing the symptoms of Cockayne syndrome has been identified.

Amy and Friends

Tel: 07949 512 968
Email: [email protected]
Website: amyandfriends.org

The Group is a Registered Charity in England and Wales No. 1119746. It provides support to children and families affected by Cockayne Syndrome. The Group offers meetings for members, an annual conference, and a weekly siblings club in Merseyside.   

Group details last reviewed December 2020.

Inheritance patterns
Usually sporadic (with no other affected family members).

Prenatal diagnosis
None.

Information and support in the UK for Coat’s disease is available from RNIB (see Sight Loss in Children)

Families can use Contact’s freephone helpline for advice and information You can also connect with other families in our closed Facebook group