Baraitser-Winter syndrome is a rare but well-defined developmental disorder recognized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, ... Baraitser-Winter syndrome is a rare but well-defined developmental disorder recognized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior-predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss (summary by Riviere et al., 2012). - Genetic Heterogeneity of Baraitser-Winter Syndrome Baraitser-Winter syndrome-2 (BRWS2; 614583) is caused by heterozygous mutation in the ACTG1 gene (102560) on chromosome 17q25.3.
In a girl with unrelated parents, Baraitser and Winter (1988) described a seemingly distinct syndrome of iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, prominent epicanthal folds, short stature, and mental retardation. This report also contained the description ... In a girl with unrelated parents, Baraitser and Winter (1988) described a seemingly distinct syndrome of iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, prominent epicanthal folds, short stature, and mental retardation. This report also contained the description of sibs with similar features who, based on a comparison of phenotypic features and inheritance patterns, Riviere et al. (2012) suggested did not have Baraitser-Winter syndrome. Riviere et al. (2012) reported on 10 children with Baraitser-Winter syndrome and mutations in the ACTB gene. Six of the 10 had short stature; 6 of 9 evaluated had postnatal microcephaly; all 9 evaluated had intellectual disability and seizures, and 4 of 8 had hearing loss; 8 of 10 had trigonocephaly; all 10 had hypertelorism and congenital ptosis, and 9 had high-arched eyebrows. Colobomata of the iris or retina were present in 6 of 10 and all 8 for whom data were available had anterior-to-posterior gradient lissencephaly of the pachygyria or pachygyria-band type. Neither familial recurrence nor consanguinity had been observed in any families, including the 18 reported by them, and no pathogenic copy-number variants had been detected using chromosome microarrays. - Phenotypic Overlap with Fryns-Aftimos Syndrome Riviere et al. (2012) noted substantial phenotypic overlap between Baraitser-Winter syndrome and some patients with Fryns-Aftimos syndrome (606155), including trigonocephaly, hypertelorism, congenital ptosis, high-arched eyebrows, broad nose, and low-set posteriorly rotated malformed ears; both have predominantly proximal contractures and a cortical malformation. One subject (11-11287), reported as patient 1 in the original report of Fryns and Aftimos (2000), was found by Riviere et al. (2012) to carry a mutation in the ACTB gene (102630.0002). - Phenotypic Overlap with Dubowitz Syndrome Johnston et al. (2013) described a 7-year-old girl with microcephaly, dysmorphic facial features, and intellectual disability, who was initially given a clinical diagnosis of Dubowitz syndrome (223370). At birth she was noted to have low-set ears, unilateral ptosis, low anterior hairline, and mild hypertrichosis. MRI of the brain at age 34 months was normal as was renal ultrasound and skeletal survey. Examination at age 4.5 years showed metopic ridging with apparent microcephaly and hoarse voice. Craniofacial findings included asymmetric positioning of the globes with left ptosis, short palpebral fissures, and apparent widely spaced eyes; posteriorly rotated ears with abnormally shaped pinnae; broad nasal root, long columella, and alae nasae flaring; prominent tongue, wide mouth, and bifid uvula. Limb findings included distally placed thumbs, small thenar eminence, camptodactlyly of digits 3, 4, and 5, and prominent fingertip pads. At age 7 years age, she was noted to have obsessive-compulsive behaviors and hyperactivity as well as severe myopia in her right eye, optic nerve asymmetry, and mild conductive hearing loss. Left vertical talus had been treated. Upon discovery of a mutation in the ACTB gene (see MOLECULAR GENETICS), her diagnosis was changed to atypical Baraitser-Winter syndrome, given the absence of some of the characteristic findings of BRWS including lissencephaly, seizures, and iris/retinal coloboma.
Riviere et al. (2012) performed whole-exome sequencing in 3 proband-parent trios and identified de novo missense changes in the cytoplasmic actin-coding genes ACTB and ACTG1 (102560) in 1 and 2 probands, respectively. The ACTB mutation in the proband ... Riviere et al. (2012) performed whole-exome sequencing in 3 proband-parent trios and identified de novo missense changes in the cytoplasmic actin-coding genes ACTB and ACTG1 (102560) in 1 and 2 probands, respectively. The ACTB mutation in the proband was a missense mutation, arg196-to-his (R196H; 102630.0002), that was also found in 6 of 15 additional affected individuals. Three additional de novo missense mutations were identified in the ACTB gene in that cohort. In a 7-year-old girl with microcephaly, dysmorphic facial features including ptosis and low-set ears, and intellectual disability, who was initially given a clinical diagnosis of Dubowitz syndrome (223370), Johnston et al. (2013) identified a de novo missense mutation in the ACTB gene (E117K; 102630.0006) and concluded that the patient had an atypical form of Baraitser-Winter syndrome without lissencephaly, seizures, or iris/retinal coloboma.