Inherited syndrome with short stature, mental retardation, ptosis, hypertelorism iris coloboma, and broad nasal bridge.
BWS 1 Synonyms: Baraitser-Wnter Syndrome 1; BWS1; Iris Coloboma, Ptosis, Hypertelorism, Mental Retardation Syndrome; Fryns-Aftimos Syndrome (Cerebro-Fronto-Facial Syndrome Type 3); Cerebro-Fronto-Facial Syndrome Type 1, 2 and 3; Pachygyria, Mental Retardation, Epilepsy and Characteristic Facies Syndrome; Mental Retardation With Epilepsy and Characteristic Facies; Cerebro-Oculo-Facial Lymphatic Syndrome (COFLS); Chromosome 7p22 Deletion Syndrome. BWS 2 Synonyms: Baraitser-Wnter Syndrome 2; BWS2.
First described in 1988 by the English physicians M. Baraitser and R. M. Winter in two siblings and an unrelated third patient.
The exact incidence is unknown, but most likely less than 60 genetically confirmed cases have been described.
Autosomal dominant inheritance. However, BWS occurs most often sporadic and is caused by de novo missense mutations in the cytoplasmic beta- and gamma-actin genes ACTB (Actin Beta) and ACTG1 (Actin Gamma-1) that have been mapped to chromosome 7p22.1 and 17q25.3, respectively. ACTB mutations are most likely associated with a more severe craniofacial phenotype (BWS Type 1), whereas ACTG1 mutations (BWS Type 2) in general result in a significantly milder facial phenotype, but are associated with significant structural brain anomalies.
Based on the typical clinical picture, but genetic studies are required to confirm the diagnosis.
Besides distinctive craniofacial findings, this multiple congenital anomaly syndrome is characterized by developmental delay, which is present in most patients and varies from mild to severe and often correlates with the extent of the anatomical brain anomalies. The most characteristic brain malformation pattern in BWS is related to the agyria-pachygyria-band spectrum. The brain may be structurally normal or exhibit frontal or predominantly central pachygyria that affects approximately two-thirds of patients. Polymicrogyria, lissencephaly, subcortical band heterotopia, or periventricular heterotopias are less common findings. Corpus callosum anomalies (ie, shortening, thickening, or absence/agenesis) are found in about 20% of patients. Seizures of variable severity affect about half of the patients, are usually associated with structural brain anomalies and often difficult to treat. Colobomata (uni- or bilateral and present in about a third of patients) affect the iris, but may also involve the retina and the optic nerve. These features may be the only ones distinguishing this syndrome from ☞Noonan Syndrome. Hypertelorism, ptosis, long and downslanted palpebral fissures, prominent epicanthic folds, thickened and edematous eyelids, and heterochromia of the iris are quite common additional ophthalmologic features, whereas microphthalmia, microcornea, aniridia, refractive errors, and nystagmus are less common. Postnatal microcephaly (in about half of the patients and usually mild), metopic ridging/trigonocephaly (due to premature closure of the metopic suture), prominently arched eyebrows, (potentially progressive) sensorineural hearing ...