Condition AZ: w

Also known as: Congenital Suprabulbar Paresis

Background

Worster-Drought syndrome is a form of cerebral palsy. The main problems occur with the mouth, tongue and swallowing (bulbar) muscles being affected. There are usually no obvious causes in the pregnancy or birth but some varieties are genetically determined. Because of the range of problems, the diagnosis is often made quite late.

Credits

Last updated October 2013 by Professor Brian Neville, Emeritus Professor of Paediatric Neurology, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK.

What are the symptoms?

Worster-Drought syndrome is a non-progressive condition. The signs and symptoms include difficulties with voluntary lip, tongue, and palate movements. Sometimes there are changes to the shape of the jaw and tooth alignment, so that dental care is important.

The first indication of the condition is usually when the baby has difficulties with feeding; those most severely affected have sucking difficulties and may require tube feeding for several months. Problems with chewing and swallowing can occur when solid foods are introduced, which may lead to inhalation of food. These difficulties may gradually improve over the first two to three years, but may also persist for many years. Dribbling is very common, but may show steady improvement during childhood. There is also severe speech delay (see entry Speech and Language Impairment). As a result of the swallowing problems, middle ear infections can be quite frequent, and may cause conductive hearing loss. A mild delay in walking and running with clumsiness of the hands with mild spasticity (stiffness) are common. Most children have mild or moderate learning and behaviour difficulties (see entry Learning Disability), which may include hyperactivity and autism spectrum condition. In a significant minority, epilepsy can also occur.

What are the causes?

Worster-Drought syndrome is caused by damage to the perisylvian area of the brain, which controls the mouth and throat muscles. The damage appears to occur in weeks 12 to 16 of pregnancy, and may be due a result of problems with blood supply to the area, or genetic vulnerability.

How is it diagnosed?

Diagnosis of Worster-Drought syndrome is based on the findings of clinical examination by a neurologist.

How is it treated?

The management of Worster-Drought syndrome is very much dependent on the degree of feeding and speech problems. In some cases, speech therapy, medication and occasionally surgical submandibular gland diversion to treat dribbling are required. Where epilepsy is present, it is treated with medication in the usual way. It is very important that cognitive development being ahead of speech is recognised.

Although separately described as a syndrome of quite severe epilepsy, bilateral perisylvian syndrome (see entry Congenital Bilateral Perisylvian syndrome) overlaps almost totally with Worster-Drought syndrome. In this latter condition, magnetic resonance imaging (MRI) shows the characteristic abnormality called perisylvian polymicrogyria. All of the clinical problems are similar to those of the Worster-Drought syndrome with the exception that the rate of epilepsy is higher. There are families with one child with this MRI abnormality and another child with typical Worster-Drought findings and a normal MRI scan. There are some genetic clues now to perisylvian polymicrogyria which are being actively explored.

Inheritance patterns and prenatal diagnosis

Inheritance patterns 
Most cases are sporadic but there have been families with more than one affected member for which the inheritance is still unclear.

Prenatal diagnosis 
None.

Is there support?

Worster-Drought Syndrome Support Group

Email: via website
Website: wdssg.org.uk

The Group is a Registered Charity in England and Wales No. 1095290. It provides information and support to families affected by Worster-Drought Syndrome or Congenital Bilateral Perisylvian Polymicrogyria. They also have a Facebook group and organise family days.

Group details last updated December 2021.

Also known as: DIDMOAD; Diabetes Insipidus; Diabetes Mellitus; Optic Atrophy

Background

Wolfram syndrome is a rare and complex genetic condition, which is sometimes referred to as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). It is classified as a progressive neurodegenerative disease (a disorder that primarily affects the body’s nervous system causing its ability to work correctly to gradually decline). By definition, all people with Classical Wolfram syndrome have both optic atrophy (blindness) and childhood-onset diabetes mellitus (onset under 16 years of age). A significant number also develop diabetes insipidus, and roughly two-thirds develop some degree of deafness, which is usually not severe. Individuals with Wolfram syndrome may also experience problems with the urinary tract, neurological symptoms and psychiatric illness (see entry Mental Health). There are also an increasing number of people affected by Wolfram-related disorders, in which one or more of the clinical complications are present with at least one mutation in the Wolfram gene. These people have a widely variable disease and variable rate of progression.

Credits

Last updated July 2015 by Dr Timothy G Barrett, Consultant Paediatric Endocrinologist, Birmingham Children’s Hospital, Birmingham, UK.

What are the symptoms?

Wolfram syndrome is characterised by:

  • diabetes insipidus – an inability to concentrate urine because of insufficient production of vasopressin (an antidiuretic hormone)
  • diabetes mellitus – an inability to convert glucose into energy the body can use. Affected people can feel thirsty and pass lots of urine. Insulin injections are essential to treat this form of diabetes
  • optic atrophy – nerve damage to the eye
  • loss of hearing with a weakening of sound frequency, intensity, tone and pitch. This may be caused by damage to the optic nerve connecting each ear to the brain.

Other symptoms that are sometimes present in Wolfram syndrome include:

  • chronic fatigue, persistent low levels of energy and a need for increased amounts of sleep
  • a form of epilepsy characterised by sudden muscle jerks without loss of consciousness (myoclonus)
  • urinary tract disorders, such as frequent urination, incontinence and bed wetting
  • colour blindness (the inability to detect and identify colours accurately). This can occur early on and may be the first sign that there is a problem with the eyes
  • emotional, behavioural and sometimes psychiatric disorders
  • delayed sexual development, more common in boys
  • digestive disorders, such as constipation or diarrhoea. Occasionally this can be severe swallowing problems. Dysfunctions in the autonomic nerves that control digestive functions may cause these symptoms
  • neurological problems owing to damage to the nervous system causing a variety of malfunctions and disorders such as ataxia (tendency to lose balance), sudden muscle jerks, abnormal eye movements, breathing problems and dizziness.

This is a list of conditions that have been reported in patients with Wolfram syndrome; most patients do not get all of these conditions, and some patients experience very few of these.

What are the causes?

Wolfram syndrome is usually caused by a mutation or defect in the WFS1 gene. This defect affects the production and function of Wolframin, a protein found all over the body and used in almost all cells.

How is it diagnosed?

If insulin-dependent diabetes mellitus and optical atrophy symptoms are present by fifteen years of age, Wolfram syndrome is presumed to exist. Genetic testing can confirm the presence of Wolfram syndrome in about 90% of patients with these features.

How is it treated?

The condition is managed by treating the symptoms as they appear. Management of diabetes mellitus can be achieved by insulin prescription, glucose monitoring and changes to diet and exercise. There is no known treatment for optic atrophy. A hearing aid may be used to alleviate hearing loss. Anticonvulsant medication is administered to avoid seizures. A tube or catheter (device used to pass urine from the bladder) may be used several times a day to eliminate urine from the bladder to prevent urine backup and incontinence (loss of bladder control). Antidepressants and psychotherapy may be used to treat depression.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Wolfram syndrome is an autosomal recessive disorder caused by a defect in the WSF1 gene.

Prenatal diagnosis
Prenatal diagnosis for Wolfram syndrome can be conducted and involves molecular analysis of the WFS1 gene. Genetic testing is available on the NHS; the central laboratory providing this is The Regional Genetics Laboratory, Birmingham Women’s Hospital, Edgbaston, Birmingham B15 2TT.

References

  • Barrett TG, Bundey SE. Wolfram (DIDMOAD) syndrome. J Med Genet. 1997;34:838-41.
  • Khanim F, Kirk J, Latif F, et al. WFS1/wolfram in mutations, Wolfram syndrome, and associated diseases. Hum Mutat. 2001;17:357-67.
  • Kredit M. Diabetes insipidus. CME. 2004;22:410-411.
  • Megighian D, Savastano M. Wolfram syndrome. Int J Pediatr Otorhinolaryngol. 2004;68:243-7.
  • Pilz D, Quarrell OW, Jones EW. Mitochondrial mutation commonly associated with Leber’s hereditary optic neuropathy observed in a patient with Wolfram syndrome (DIDMOAD). J Med Genet. 1994;31:328-30.
  • Ryan EA. Treating Diabetes Mellitus. The Canadian Journal of CME. 2004:Sept;103-108.

Is there support?

WellChild Wolfram Syndrome Family Coordinator

Tel: 01242 548 762
Email: rachelbates@wellchild.org.uk
Website: wellchild.org.uk/get-support/information-hub/wolfram-syndrome-resources/

Established in 2012, the WellChild Wolfram Syndrome Family Coordinator provides a listening ear, gives advice and information, and links families to each other and local services. The service is available to families with children under 18 with the syndrome. The Family Coordinator is able to refer children to specialist clinics at Birmingham Children’s Hospital and can act as an advocate for families’ needs.

Group details last updated July 2015.

Wolfram Syndrome UK Support Group

Tel: 01903 211 358
Email: families@wolframsyndrome.co.uk
Website: wolframsyndrome.co.uk

The Group is a Registered Charity in England and Wales No. 1152445. It provides information and support to families affected by Wolfram Syndrome in the UK. The Group offers an online forum and holds an annual meeting for families and medical professionals. 

Group details last updated July 2015.

Also known as:  4p- syndrome; Chromosome 4p- syndrome; Pitt-Rogers-Danks syndrome

Background

Wolf-Hirschhorn syndrome is a rare chromosome disorder. The syndrome is caused by a missing section (deletion) of genetic information from the tip of the short arm of chromosome 4.

Credits

Last updated August 2015 by Dr O Quarrell, Consultant in Clinical Genetics, Department of Clinical Genetics, Sheffield, 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 is provided is for education/information purposes and is not designed to replace medical advice by a qualified medical professional.

What are the symptoms?

There is a wide variation in the degree of problems seen in this condition. Children with Wolf-Hirschhorn usually have:a low birth weight

Affected individuals tend to have similar facial features. These may include a broad bridge to the nose, wide-spaced eyes and a small chin.

Learning difficulties (see entry Learning Disability) are variable and can be moderate to severe.

Children with Wolf-Hirschhorn syndrome may be born with some other congenital problems. The most commonly recognised include: cleft lip and/or palate, congenital heart disease, (see entry Heart Defects), kidney problems, Kidney disease, eye anomalies such as coloboma, undescended testes and hypospadias.

What are the causes?

Wolf-Hirschhorn syndrome is caused by a missing section (deletion) of genetic information from the tip of the short arm of chromosome 4. Some children have a deletion of genetic material from the tip of chromosome 4 which is replaced by extra material from another chromosome – this is called an unbalanced translocation (unbalanced rearrangement). It is the loss of genetic material that causes the features of this condition and is usually more important than gain of extra material from another chromosome.

How is it diagnosed?

A blood sample is taken. The loss of genetic material used to be seen using a microscope but nowadays, microarray comparative hybridisation (array-CGH) and fluorescent in situ hybridisation (FISH) are the techniques used.

Once a child has been diagnosed, the chromosomes of the parents should be checked. These will be normal in the majority of cases, indicating that the deletion or unbalanced translocation occurred by chance (sporadic). In the remaining cases, there may be a chromosome translocation (rearrangement) which one parent may carry in a balanced form.

How is it treated?

Management of the condition is aimed at alleviating any symptoms and supporting those affected so they can reach their full potential. There is no cure for the condition. Epilepsy may be treated with anticonvulsant medication. In some cases a feeding tube is put into the stomach. Specialist support in education will be required. Heart defects, kidney problems or eye problems will need to be assessed and managed by the appropriate specialist. It is difficult to make a prediction but some children survive well into adulthood. Although treatment is symptomatic and supportive it may help if the local doctor makes periodic medical checks; for example, simple checks of kidney function.

Inheritance patterns and prenatal diagnosis

Inheritance patterns

If the loss of genetic material is sporadic, a couple’s chance of having another affected child is low (less than 1%). In the cases in which one parent carries the rearrangement (translocation) in a balanced form, the chance of having a second affected child is assessed on an individual basis. Information and support is available for affected families through a genetics centre.

Prenatal diagnosis

Chorionic villous sampling from 11 weeks of pregnancy and amniocentesis from 15 weeks of pregnancy are available. If one parent has a translocation in a balanced form then pre-implantation genetic diagnosis may be possible but the couple have to meet certain criteria to access NHS funding for this treatment.

Is there support?

Wolf-Hirschhorn Syndrome Support Group

Tel: 07917 334407
Email: sdall04@yahoo.com
Website: whs4pminus.co.uk

The Group is a Registered Charity in England and Wales No. 1038219. It provides information and support to families affected by Wolf Hirschhorn Syndrome and holds a national meeting every two years.

Group details last updated May 2017.

Also known as: Infantile Hypercalcaemia; Williams-Beuren syndrome

Background

Williams syndrome is a rare congenital (present at birth) condition that is caused by missing genetic material from chromosome 7. Individuals with Williams syndrome are affected to differing degrees and display typical facial features as well as developmental delay.

Credits

Medical text written July 2011 by Dr K Metcalf, Consultant Clinical Geneticist, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

What are the symptoms?

Individuals with Williams syndrome display typical facial features, including:

  • prominent cheeks
  • upturned nose
  • wide mouth
  • irregular, widely spaced teeth.

Children may have a heart problem, typically supravalvular aortic stenosis, peripheral pulmonary artery stenosis or both. These are often present at birth or develop in early childhood.

Some children develop hypercalcaemia (abnormally high levels of calcium), usually within the first two years of life but this tends to correct itself after the third year. Hypercalcaemia may cause failure to thrive, feeding problems, irritability, vomiting, constipation and kidney problems. A number of other health problems are more common in Williams syndrome. Monitoring for high blood pressure is particularly important throughout life.

Children with Williams syndrome are usually developmentally delayed, with most having moderate learning difficulties (see entry Learning Disability). They may be slow to develop language, but by school age their spoken language is usually a relative strength. They are often clumsy and have difficulties in the integration of visual-spatial information. Most children with Williams syndrome are outgoing and socially disinhibited towards adults, including strangers, but they tend to have poor relationships with other children.

Typical behaviour difficulties include overactivity, poor concentration and distractibility, excessive anxiety, attention seeking behaviours and high rates of preoccupations and obsessions. Many children are hypersensitive to particular sounds, a condition known as hyperacusis, including electrical noises (eg vacuum cleaners).

Despite their relatively good verbal and social skills, most adults with Williams syndrome are unable to live independently and require ongoing support and supervision in everyday activities.

What are the causes?

Williams syndrome is a sporadic syndrome that occurs because of a microdeletion of chromosome 7 (7q11.23) involving 26 to 28 genes. This deletion results in the protein elastin not being produced. Elastin is responsible for providing strength and elasticity to blood vessel walls.

How is it diagnosed?

Clinical diagnosis is based on a variety of characteristics common to Williams syndrome, including the typical facial features, heart problems, poor feeding and developmental delay.

Williams syndrome is confirmed by a taking a blood sample, which is then tested to see if the relevant microdeletion is present. Fluorescent in situ hybridisation (FISH) or microarray comparative hybridisation (array-CGH) are two tests that can be used to see if there is material missing from chromosomes.

How is it treated?

There is no cure for Williams syndrome. Hypercalcaemia can be addressed by a low-calcium diet. Individuals will need to be managed by a multidisciplinary team of specialists who can help support their medical, educational and social care needs.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Most cases are sporadic and due to a new chromosome deletion arising in the child. Children of affected individuals however would be expected to have a 50 per cent chance of inheriting Williams syndrome.

Prenatal diagnosis
For couples who already have a child with Williams syndrome seeking reassurance, or for pregnancy in someone affected by Williams syndrome, prenatal diagnosis by FISH testing of chorionic villus biopsy or amniocentesis is possible.

Is there support?

Williams Syndrome Foundation

Tel: 01732 365 152
Email: enquiries@williams-syndrome.org.uk
Website: williams-syndrome.org.uk

The Foundation is a Registered Charity in England and Wales No. 281014. It provides information and support for individuals with Williams Syndrome, their families and professionals. The Foundation actively supports research into the educational, behavioural, social, scientific and medical aspects of the Syndrome. 

Group details last updated September 2014.

As Williams syndrome is a metabolic disease, support and advice are also available from Climb (see entry Inherited Metabolic diseases).

Background

West syndrome is the term used to describe a type of epilepsy which most typically starts in the first year of life, between four and 8 months of age. It may, however, start younger than this.

Credits

Medical text written November 2002 by Dr J Livingston, Consultant Paediatric Neurologist, Leeds General Infirmary, Leeds, UK. Last updated October 2015 by Professor Brian Neville, Emeritus Professor of Paediatric Neurology, UCL Institute of Child Health and Great Ormond Street Hospital, London, UK.

What are the symptoms?

The hallmark of West syndrome is the occurrence of a particular type of epileptic seizure called a spasm. Spasms typically produce a sudden jerk of the body followed by stiffening of the limbs. Different types of spasms may occur, but most typically a child will suddenly bend forward with elevation of the arms or legs. These attacks usually occur in runs or clusters when one spasm occurs after another at five to 15 second intervals for a period of several minutes. These episodes may occur several times per day. Very commonly, when a child starts to have spasms, there is change in their behaviour and they stop vocalising and making visual contact.  This commonly persists.

What are the causes?

West syndrome is not one condition but is a symptom of many different brain disorders. A cause can be found in most children, but in a small proportion no obvious cause can be identified. Sometimes West syndrome occurs in children with severe abnormalities of the brain such as congenital infections, severe brain injury due to birth asphyxia (lack of oxygen) or severe malformations of the brain. Sometimes very rare genetic or metabolic diseases cause West syndrome. One of the most common causes of West syndrome is tuberous sclerosis. Chromosome abnormalities may also cause West syndrome. It is therefore very important when a diagnosis of West syndrome is made that an extensive search is carried out to find the underlying cause.

How is it diagnosed?

The diagnosis of West syndrome is based on the occurrence of infantile spasms and the presence of a very abnormal EEG (brain wave recording). The most typical EEG abnormality is called ‘hypsarrhythmia’; however, other abnormal patterns may occur.

How is it treated?

The most common treatments for West syndrome are vigabatrin (an anti-epileptic drug) or corticosteroids (prednisolone, hydrocortisone, corticotrophin, or adrenocorticotropin [ACTH]). In many children the spasms will stop with appropriate treatment; however, after a period of time they will often relapse and require a change of treatment. Some would now suggest treatment with both drugs.

Inheritance patterns and prenatal diagnosis

Inheritance patterns 
This depends on the underlying cause and genetic advice should be sought.

Prenatal diagnosis 
None.

Is there support?

West Syndrome Support Group

Tel: 01252 654 057
Email: kimdenise44@gmail.com

The Group is run by parents and offers support and a sympathetic ear to families of children affected by West Syndrome.

Group details last updated February 2016.

UK Infantile Spasms Trust

Email: via website
Website: ukinfantilespasmstrust.org

The Trust is a Registered Charity no. 1172167. They provide information and support to children, parents and carers of those affected by Infantile Spasms or West Syndrome. They also offer an active Facebook group. They aim to promote research and raise awareness of the conditions.

Group details added April 2017.

Overview

Waardenburg syndrome (WS) is a genetic condition that causes hearing impairment (see entry Deafness) from birth, colour changes in the iris of the eye, hair, and skin, and a characteristic facial appearance. Some individuals may have a white forelock (white lock of hair growing above the forehead) and slightly widely spaced eyes as well as different coloured eyes (usually one blue and one brown). Infrequently, WS may be associated with other conditions such as congenital heart disease (such as a ‘hole in the heart’) or the gastrointestinal problems of Hirschsprung’s disease. Four main types of WS exist based upon detection of the change (mutation) in the causative gene. Diagnosis will be made based on common symptoms being present. No specific management is available for Waardenburg syndrome. Attention must be paid to any hearing loss, and hearing aids and appropriate schooling may be needed. Special diets and medicines to keep the bowel moving are required by those who have constipation. The different types of WS 1-4 may be inherited in different ways based on the causative gene. Affected families should be referred to a genetics centre for information and support.

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 January 2012 by Dr Adam Shaw, Contact a Family Medical Advisory Panel.

Is there support?

There is no support group for Waardenburg syndrome in the UK. Families can use Contact’s freephone helpline for advice, information and, where possible, links to other families. You can also join our private Facebook group.