ACTB-related Syndrome; Baraitser-Winter Syndrome 1; Baraitser-Winter Syndrome 2; BWCFF Syndrome; BWS1 Syndrome; BWS2 Syndrome; Fryns-Aftimos Syndrome

Baraitser-Winter syndrome (BWS) is a condition that affects the development of many parts of the body, particularly the face and the brain. Structural brain abnormalities are also present in most people with BWS. The most frequent brain abnormality associated with BWS is pachygyria, which is an area of the brain that has an abnormally smooth surface with fewer folds and grooves. Less commonly, affected individuals have lissencephaly, which is similar to pachygyria but involves the entire brain surface. These structural changes can cause mild to severe intellectual disability, developmental delays, and seizures. BWS is caused by autosomal dominant de novo (new) mutations in the ACTB (type 1) or ACTG1 (type 2) gene.

Diagnostic testing: The diagnosis of BWS is based on:

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  Clinical examination;

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  Symptoms;

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  Genetic testing for mutations in the ACTB (type 1) or ACTG1 (type 2) gene;

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  Magnetic resonance imaging (MRI) of the brain; and

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  Ophthalmology evaluation.

Physical findings: Signs and symptoms of BWS may include:

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  A long space between the nose and upper lip;

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  Bulbous nose (a nose that may appear disproportionately large) with broad nasal tip and prominent nasal bridge;

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  Developmental delay;

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  Droopy eyelids (ptosis);

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  Congenital nonmyopathic ptosis;

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  Ear abnormalities;

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  Abnormalities of the kidneys and urinary system;

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  Large eyelid opening;

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  Limited movements of large joints (i.e. elbows and knees);

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  Ocular coloboma (an area of missing tissue in the eye);

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  Pointed chin;

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  Prominent metopic ridge, and highly arched eyebrows;

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  Sensorineural hearing loss;

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  Seizures;

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  Short stature;

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  Muscle wasting in the shoulder girdle; and

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  Widely spaced eyes.

ICD-9: 317-319.99; 759.89

ICD-10: Q87.0; Q87.89

The prognosis for children with BWS varies depending on the severity of their symptoms. Neuromuscular involvement tends to worsen over time, with progressive muscle wasting and weakness, progressive scoliosis, osteoporosis, and loss of ambulation in the fifth decade of life.

Neurological decline with feeding difficulties and recurrent pneumonia may occur as the individual ages. Life span may be reduced due to acute ileus (functional intestinal obstruction in which muscles fail to contract causing a buildup of gas and other liquid or solid content).

Currently there is no cure for BWS. Treatment is symptomatic, involving neurological care for seizures and specialized support for developmental delays (physical/speech therapy). Abnormal vision is treated by an ophthalmologist; hearing aids may be prescribed for hearing deficits. Muscle wasting and joint limitation may require orthopedic monitoring and physical therapy to slow progressive joint ankyloses and scoliosis. Gastrointestinal (GI) disorders associated with BWS, such as intestinal malrotation, chronic intestinal pseudo-obstruction, and feeding difficulties—are primarily treated by pediatric gastroenterologists. Treatment focuses on managing the symptoms and improving the quality of life.

Suggested MER for Evaluation:

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  Clinical history and examination that describes the clinical features of the impairment;

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  Genetic testing confirming gene mutations of ACTB (type 1) or ACTG1 (type 2) gene;

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  Neuroimaging; and

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  Neurological assessment.

Suggested Listings for Evaluation:

1.18

2.10

2.11

10.06

11.02

12.05

101.18

101.24

102.10

102.11

110.08B

111.02

111.09

112.05

112.14

1.15

11.07