Condition AZ: b

There is no support group for Bloom syndrome in the UK. Families can use Contact’s freephone helpline for advice and information. You can also meet families online in our closed Facebook group

Epispadias
Children with epispadias may have normal urinary control, but the majority of both boys and girls with epispadias are incontinent. In epispadias, both the bladder and bladder neck (control mechanism) can be responsible. Consequently, once the penis/female urethra have been corrected many children still require further surgery on the control mechanism to achieve normal control of urine.

Bladder exstrophy
The characteristic features of bladder exstrophy are: a bladder that opens directly onto the abdominal wall; abnormal genitalia; and where the bony part of the pelvis has remained open. The surgical repair is normally perestablished in three stages. Firstly, the bladder is closed; this is undertaken soon after birth, to prevent excessive damage. To aid closure, operations on the bony pelvis may be performed. Secondly, at six to 12 months of age, the epispadias repair is carried out. In boys, the penis is epispadic and is corrected surgically during the second stage of the repair. In girls, the clitoris is divided into two halves with the urethra running between. In addition, the vagina is slightly more forward than it usually is, this is often able to be corrected at the initial repair. Finally, between three to four years of age bladder neck reconstruction is carried out, if necessary. Increasingly, the second and third stages are being combined in the first year of life. Some surgeons are now challenging this staged approach.

Cloacal exstrophy
Cloacal exstrophy is the most severe end of the epispadias-exstrophy complex , consequently the chance of normal voiding is extremely small. In addition to problems with the urine, the bowel and spine are often involved. Reconstructive surgery is usually carried out in the first few weeks of life, but these children often have long-term problems gaining any urinary or faecal control. If the penis is not able to be adequately reconstructed in a boy, it may be necessary to perform bilateral gonadectomies and a feminising genitoplasty and the child be brought up as an XY female, although the child will be infertile.

The diagnosis is usually made at birth, or increasingly prenatally, with the exception of female epispadias that may present with urinary incontinence.

Treatment in all cases this is usually by surgery details can be found in the background information under ‘symptoms’.

Inheritance patterns
None known.

Prenatal diagnosis
At present difficult but with increasing experience, prenatal diagnosis is possible.

There is no support group for bladder exstrophy in the UK. Families can use Contact’s freephone helpline for advice and information.  You can also meet other families online in our closed Facebook group

Periods of mania may develop quite rapidly over a period of a few days and last for a week or longer. Aspects of mania may include a number (usually three or four) of the followingoccurring together:

• unreal ideas of an individual’s importance
• need for less sleep than normal
• heightened energy
• increased talkativeness
• unrealistic new activities
• inappropriate behaviour
• distracted and agitated behaviour
• mood change affecting personal and school or college life
• risky behaviour leading to financial difficulties
• possible alcohol and drug related misuse.

In bipolar affective disorder the depressive period lasts for at least two weeks and includes at least five of the following:

• constant low mood for most of the day and nearly every day
• sleep disturbance
• weeping and extreme sadness
• tiredness and lack of energy
• lack of interest in most activities
• inability to concentrate
• feelings of guilt, worthlessness and suicide
• appetite changes
• problems in affection and personal relationships.

The cause of bipolar affective disorder is not known, but it is thought that genetic and environmental factors are involved. Stress factors may play a part in the further onset of the disorder in previously diagnosed people.

A diagnosis of bipolar affective disorder type I describes an illness with one or more manic episodes or mixed episodes. People often have one or more major depressive episodes.

Bipolar affective disorder type II is characterised by the occurrence of one or more major depressive episodes accompanied by at least one hypomanic episode.

This usually requires a psychiatrist to complete an assessment to provide a diagnosis and treatment plan.

Treatment with medication is either preventative or symptomatic (treating episodes of mania and depression when they occur). Medication is usually mood stabilising drugs such as atypical antipsychotics (eg aripiprazole, risperidone, olanzapine, lurasidone), lithium and antiepileptic mood stabilizers (eg carbamazepine, sodium valproate and lamotrigine). Sodium valproate should not be used in women of childbearing potential, or in post-pubertal girls, as it can be harmful to the unborn baby. It is often necessary to combine mood stabilisers in order to get good control of the symptoms. These medications can be taken as a long-term preventative measure or as a symptomatic medication.

Inheritance patterns
It is thought that an individual’s genetic make-up might be involved as there is a higher than average chance of developing the condition if other members of the family are affected.

Prenatal diagnosis
None. 

Bipolar UK

Tel: 0333 323 3880
Email: [email protected]
Website: bipolaruk.org.uk

Bipolar UK is a Registered Charity in England and Wales No. 293340. It provides information and support to people affected by bipolar and associated illnesses. Offers support groups across the UK, an active eCommunity and a Support Line.

Group details last reviewed December 2022.

Features of BWS include:

• overgrowth (a high birth weight, and/or children who are bigger than other children)
• hemihypertrophy (one side of the body grows more than the other)
• macroglossia (a large tongue which may cause breathing, feeding or speech difficulties)
• Abdominal wall defects ranging from exomphalos (a hole in the abdomen that allows abdominal organs to poke through the navel see entry Abdominal Wall Defects) to umbilical hernia
• hypoglycaemia (low blood sugar) after birth
• characteristic facial appearance
• visceromegaly (abnormally large abdominal organs)
• kidney abnormalities.

Children with BWS are at an increased risk of developing several types of cancerous and noncancerous tumours, such as a rare form of kidney cancer called Wilms’ tumour, rhabdomyosarcoma (a cancer of muscle tissue), and hepatoblastoma (a form of liver cancer). Not all children with BWS are at risk for Wilms’ tumour but those that are should be screened regularly for these tumours. For those children who do develop a Wilms’ tumour the treatment is generally successful.

The genetic causes of BWS are complex. The condition usually results from the abnormal regulation of genes in a particular region of chromosome 11.

Diagnosis would be made by identifying the key symptoms that indicate a child has the syndrome. Blood tests can help identify low blood sugar levels. Magnetic resonance imaging (MRI) or computed tomography (CT) scans of the abdomen may be necessary as well as ultrasound scanning of the abdomen and X-rays of the long bones.

Genetic studies can be carried out to look for abnormalities in chromosome 11.

Treatments may be given to improve symptoms; at the moment there is no cure for the condition. Infants with low blood sugar may be treated by fluids given through a vein (intravenous solutions). Problems with the abdominal wall may need to be repaired surgically. Children at risk for tumours can undergo regular screening. Children may experience difficulty with feeding and breathing, especially at night due to a large tongue, so strategies to aid these activities may need to be put in place.

Inheritance patterns
Most cases of the condition occur by chance (sporadically). However in some families, BWS may be familial (passed down from one family member to another). As the genetics of the condition is so complex, affected families should be referred to a regional genetics centre for information and support.

Prenatal diagnosis
When a chromosome 11 abnormality has been detected in familial cases this might be checked for using chorionic villus sampling (CVS) or amniocentesis. Ultrasound screening may detect exomphalos if present.( see entry Abdominal Wall Defects).

Beckwith-Wiedemann Support Group

Tel: 01258 817 573 or 07889 211 000
Email: [email protected]
Website: bwssupport.com

The Group provides information and support for parents of children with BWS in the UK. It aims to promote public and professional awareness of the condition and to support and encourage research. The Group is in contact with sister groups in Italy and Spain. 

Group details last reviewed December 2020.

Features of BMD include:

• progressive muscle weakness leading to difficulty with physical activities such as standing up from sitting, climbing up steps, running or walking and, usually later, weakness affecting the upper arms and shoulders
• joint contractures can arise from the tightening of tendons, especially the Achilles tendon
• pseudohypertrophy (enlargement without additional strength) of muscles in the calves and elsewhere
• cardiomyopathy (see entry Cardiomyopathies in children)
• in the later stages of the disease, respiratory muscle weakness may lead to chest infections.

There may also be learning and/or behaviour problems in some children, including difficulty in focusing attention, verbal learning and memory.

BMD is caused by mutations in the dystrophin gene. Female carriers of BMD are usually healthy. However, a small number of female carriers of the defective gene are ‘manifesting carriers’ (females who experience some of the effects of the disorder). These problems are usually milder than in a male and are likely to develop later in life. Occasionally, a manifesting carrier may have significant muscle weakness. Manifesting carriers may also have heart problems, which appear as shortness of breath or inability to do moderate exercise. The heart problems, if untreated, can be serious.

A test will be made for raised levels of creatine kinase (CK) in the blood. Elevated levels of CK are found in the blood of most individuals with BMD from childhood, sometimes from the newborn period. Further tests will be performed to confirm that the muscle weakness arises from destruction of muscle tissue rather than nerve damage. These may include:

• genetic tests to look for mutation(s) in the dystrophin gene, usually carried out on a blood sample
• electrical tests carried out on a muscle and/or nerve
• muscle biopsy (examination of tissue in the pathology laboratory).

Currently there is no known cure for BMD, so treatment aims to control symptoms and maintain quality of life. Physiotherapy may help to maintain muscle strength and the range of joint movement; orthopaedic devices such as braces and the use of wheelchairs can improve mobility. Surgery may sometimes be helpful if tendon contractures are problematic. Medication may also be prescribed for cardiac problems.

Inheritance patterns
BMD is inherited as an X-linked recessive trait. The dystrophin gene is located on the X chromosome, which results in mainly males being affected with the condition.

Prenatal diagnosis
This is usually possible where it is known that BMD affects the family and where the family’s particular mutation in the dystrophin gene is known. Preimplantation genetic testing (or diagnosis) (PGT or PGD) may also be used by a female carrier to avoid transmitting the condition to her children.

Information and support in the UK for Becker muscular dystrophy is provided by Muscular Dystrophy UK (see entry Congenital Muscular Dystrophy).

Symptoms of most kinds of Batten Disease include loss of vision, epilepsy (see entry Epilepsy syndromes in Childhood) and progressive loss of abilities, including walking, speech and eating normally. A number of different genetic types are known.  In the UK, CLN2 (late infantile) and CLN3 (juvenile) are the most common:

• CLN1 disease, infantile: onset usually between six months and two years with developmental delay and seizures. There are some cases where the onset is much later in childhood or adulthood.
• CLN2 disease, late infantile: onset between two and four years with seizures and slowing down of developmental progress.  Atypical cases are recognised with later onset of learning difficulties and movement problems and slower disease progression (some of these have been diagnosed as spinocerebellar ataxia).
• Variant late infantile forms (CLN5, 6, 7, 8 diseases and others): onset between two and six years, often with challenging behaviour, slowed developmental progress and then seizures
• CLN3 disease, juvenile: onset of deteriorating vision between five and nine years. Children remain healthy for several years but then develop epilepsy and slowly become more dependent on others .  Sadly, death can occur at any time from the late teens to the mid-thirties
• Early adult dementia

A number of different genetic mistakes (mutations) cause the different forms of Batten disease. The different genes are called CLN1, CLN2, CLN3, CLN4, CLN5, CLN6, CLN7, CLN8, CLN10, CLN11, CLN12, CLN13 and CLN14. In CLN1, CLN2 and CLN10 diseases the genetic changes result in a shortage of crucial enzymes in the parts of the cells called lysosomes.

The first symptoms of late infantile and variant late infantile types of Batten disease (CLN2, CLN5, CLN6, CLN7, CLN8 and others) are often slowing of developmental progress and epilepsy in young children. Children are seen by paediatricians and often referred to paediatric neurologists who arrange for lots of tests to be done including brain scans, electroencephalograms (EEGs; ‘brain wave’ tests) and blood and urine tests to look for many different causes. The Batten disease tests are usually done at the same time as many other tests. An enzyme or genetic test confirms the diagnosis of one of the types of Batten disease.

CLN3 disease (also known as juvenile Batten disease) may be first suspected during an eye examination. An optician or ophthalmologist may detect abnormalities in the back of the eye. Referral will be made to a neurology specialist for further testing and diagnosis. Diagnosis is usually made following blood tests, including genetic tests.

Management of all types of Batten disease will be directed towards controlling symptoms and providing support to those affected and their families. Currently, there is no known cure for these conditions, although research is underway and new treatments are becoming  available in some countries. Seizures are treated with anticonvulsant medications. Physical therapy and occupational therapy may be of help in maintaining movement and muscle function. Appropriate education, short-breaks, care and family support are essential.  Further information about clinical trials and new or experimental treatments is available on the Batten Disease Family Association website.

Inheritance patterns
Autosomal recessive for all the childhood variants, though it is thought that some of the rare adult forms can be inherited in an autosomal dominant way. Affected families should be referred to a genetics centre for information and support.

Prenatal diagnosis
Prenatal diagnosis using chorionic villus sampling is available in the UK if the genetic mutation in a family is already known.

Batten Disease Family Association

Tel: 07876 682589
Email: [email protected]
Website: bdfa-uk.org.uk

The Association is a Registered Charity in England and Wales No. 1084908. It offers informed guidance and support to everyone who is affected by Batten disease, and the professionals who work with them.

Group details last reviewed December 2020.

Primary features:

• rod/cone dystrophy – a progressive eye condition, which can lead to blindness
• obesity, childhood-onset with fat distributed particularly around the trunk (middle of body)
• polydactyly (extra fingers and/or toes)
• hypogenitalism (underdeveloped genitals)
• mild-to-severe learning difficulties (see entry Learning Disability)
• renal abnormalities (such as cysts) and impaired renal function
• endocrine disturbances that involve pituitary, thyroid, adrenal glands, the ovaries and testes (may lead to subfertility).

Secondary features may include:

• speech problems
• developmental delay (see entry Global Developmental Delay)
• behavioural abnormalities
• eye abnormalities, including strabismus (cross-eyed), cataracts, and astigmatism (abnormally shaped eyeball)
• balance disturbance and broad gait (walking)
• reduced fine motor skills
• brachydactyly (short fingers and/or thumbs)
• syndactyly (digits joined together)
• diabetes mellitus
• dental and roof of mouth abnormalities (high-arched palate)
• cardiovascular anomalies (high blood pressure, abnormal heart valves)
• hepatic (liver) problems
• olfactory dysfunction (lack of ability to smell)
• Situs inversus (misplacement of internal organs – eg mirror-image).

In children with BBS, night-blindness usually occurs by seven to eight years of age and total blindness is typical by the third decade.

Twenty-one genes are known to be associated with BBS. Two mutations in any one of these genes are enough to manifest the syndrome. Not all people (~15%) with BBS have mutations in these known genes, so more remain to be discovered. It is now known that these mutations result in abnormal cilia function. These are finger-like projections that are important for cells to sense their surrounding environment and communicate with one another.

Diagnosis is made on the basis of clinical features initially. A diagnosis can be confirmed by testing DNA to see if the mutation(s) causing the condition lie in one of the 21 genes already identified.

There is no cure for BBS. Treatment aims to reduce the symptoms experienced by a person with BBS. Regular eye check-ups by an ophthalmologist will highlight any existing problems. Visual aids and educational programmes can assist with visual difficulties. Obesity is managed with diet, exercise and behavioural therapies. Hypercholesterolemia (high cholesterol) and diabetes mellitus may be treated with the appropriate medications and changes to diet. Early intervention, special education provision and speech and language therapy can help with learning.

In cases of severe renal (kidney) abnormality, renal transplantation may be required. Genital abnormalities, for example hypospadias, may be surgically corrected. Hormone replacement therapy can be initiated for hypogonadism (where sex glands produce little or no sex hormones). Cardiac abnormalities need to be monitored and may be corrected surgically. Surgery to remove extra digits prevents difficulties walking and balancing and poor fitting of footwear.

Inheritance patterns
Inheritance is autosomal recessive (two mutations required to manifest the disease).

Prenatal diagnosis
A number of features (e.g. extra digits, hyperechogenic kidneys) can be determined on high-definition ultrasound scanning of the fetus. This, however, is not a test of exclusion of the condition. If two gene mutations can be identified in a BBS family then a molecular genetic DNA test can be offered prenatally.

Bardet-Biedl Syndrome UK (Formerly LMBBS)

Tel: 07591 206680
Email: [email protected]
Website: bbsuk.org.uk

The charity is a Registered Charity in England and Wales No. 1027384 and in Scotland No. SCO41839. It provides information and support for people with Bardet-Biedl Syndrome and their families and carers throughout the UK. The Charity holds an annual family conference and activities throughout the year and through the BBS UK Clinics provides further support and facilitation services alongside the NHS.

Group details last updated April 2018.

There is no support group for Bannayan-Riley-Ruvalcaba syndrome in the UK. Families can use Contact’s freephone helpline for advice and information. You can also meet other families online in our closed Facebook group

The features of Barth syndrome are very variable but the majority of patients develop heart failure (cardiomyopathy) within the first year. Heart failure in young children tends to cause rapid, laboured breathing and poor feeding. Sweating with feeds is common. The heart tends to be swollen like a floppy bag (called dilated cardiomyopathy or DCM), and may have a thickened white inner lining (known as endocardial fibroelastosis or EFE) or deep pockets in the wall of one of the major pumping chambers (called left ventricular non-compaction or LVNC). Potentially serious cardiac rhythm problems may occur and there may be a previous family history of sudden death.

The blood neutrophil count varies unpredictably between low and normal but can be normal at all times in 10% of affected males. When it is very low (termed severe neutropenia), boys may develop sore red gums (complaining when their teeth are brushed), mouth ulcers, nappy rashes and bacterial infections. Muscles are weak and affected babies are often slow to sit, walk or run (called ‘delayed motor milestones’ or ‘motor delay’). They may have difficulty when rising from sitting on the floor, have a rather waddling gait on running and difficulty in kicking a football.

Barth syndrome is caused by mutations in a gene called tafazzin (TAZ), which is located on the X chromosome. Although the mechanism is not clearly understood, this seems to affect the cell’s ability to produce energy, explaining weak muscles, fatigue, poor stamina and heart muscle failure.

Analysis of phospholipids called cardiolipins in blood or tissue samples, can be obtained via the NHS national service for the disease. Patients with abnormal cardiolipin ratios are then offered sequencing of the causative TAZ gene.

Often the heart failure can be controlled by drug treatment (although boys may stabilise for a period but then deteriorate unexpectedly). Heart transplantation may be necessary if heart failure cannot be controlled.

Preventative daily antibiotics will reduce the risk of bacterial infection if boys are severely neutropenic. However, many boys require the use of a medicine called granulocyte colony stimulating factor (G-CSF), usually given three times per week, to prevent bacterial infections and improve quality of life.

Inheritance patterns
Barth syndrome is inherited as an X-linked recessive trait. Detailed genetic counselling is advisable when Barth syndrome is identified in a family.

Prenatal diagnosis
Prenatal diagnosis is possible at an early stage in pregnancy in families where the mutation is known. Several blood tests taken from a mother after seven weeks of pregnancy can now identify whether she is carrying a male foetus with at least 98% certainty. This may help parents in their decision about going on to a test such as chorionic villus sampling (from 11 weeks of pregnancy onwards) or amniocentesis (from 15 weeks onwards). These tests exclude the disease by testing for the change in the TAZ gene but carry a very small risk of causing miscarriage.

Barth Syndrome Trust

Tel: 01794 518785
Email: via website
Website: barthsyndrome.org.uk

The Trust is a Registered Charity in England and Wales No. 1100835, established in 2003. It provides information and support to those affected by Barth syndrome and their families. The Trust aims to raise awareness of the syndrome amongst health professionals and raises funds to support research. It is involved in delivering a specialised service through the Bristol Royal Hospital for Children.

Group details last checked March 2017.