Baraitser-Winter Syndrome Research Articles

Severe forms of Baraitser–Winter syndrome are caused by ACTB mutations rather than ACTG1 mutations

ACTB and ACTG1 mutations have recently been reported to cause Baraitser-Winter syndrome (BRWS) - a rare condition characterized by ptosis, colobomata, neuronal migration disorder, distinct facial anomalies and intellectual disability. One of the patients carrying an ACTB mutation was previously diagnosed with Fryns-Aftimos syndrome (FAS), which is a rare and severe, multiple congenital anomaly (MCA) syndrome whose symptoms partially overlap with that of BRWS. However, several patients with Fryns-Aftimos were considered not to fit into the ACTB and ACTG1 spectrum because of their severe impairment and additional malformations. We report on three patients who had been diagnosed with FAS. All three patients carry a mutation in the ACTB gene. On the basis of the ACTB mutations and analysis of the clinical findings, we reclassify the diagnosis of these patients as severe BRWS. We suggest that mutations in ACTB cause a distinctly more severe phenotype than ACTG1 mutations, despite the structural similarity of beta- and gamma-actins and their overlapping expression pattern. We expand the spectrum of BRWS and confirm that FAS is not a separate entity but an early and severe manifestation of BRWS.

Functional Analysis of a De NovoACTBMutation in a Patient with Atypical Baraitser-Winter Syndrome

Exome sequence analysis can be instrumental in identifying the genetic etiology behind atypical disease. We report a patient presenting with microcephaly, dysmorphic features, and intellectual disability with a tentative diagnosis of Dubowitz syndrome. Exome analysis was performed on the patient and both parents. A de novo missense variant was identified in ACTB, c.349G>A, p.E117K. Recent work in Baraitser-Winter syndrome has identified ACTB and ACTG1 mutations in a cohort of individuals, and we rediagnosed the patient with atypical Baraitser-Winter syndrome. We performed functional characterization of the variant actin and show that it alters cell adhesion and polymer formation supporting its role in disease. We present the clinical findings in the patient, comparison of this patient to other patients with ACTB/ACTG1 mutations, and results from actin functional studies that demonstrate novel functional attributes of this mutant protein.

Baraitser Winter's syndrome and GH deficiency

Baraitser Winter's syndrome and GH deficiency

De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome

Brain malformations are individually rare but collectively common causes of developmental disabilities1–3. Many forms occur sporadically and have reduced reproductive fitness, pointing towards a causative role for de novo mutations4,5. Here we report our studies of Baraitser-Winter syndrome, a well-defined syndrome characterized by distinct craniofacial features, ocular colobomata and a neuronal migration defect6,7. By using whole-exome sequencing in three proband-parent trios, we identified de novo missense changes in the cytoplasmic actin genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in fifteen additional patients revealed disease-causing mutations in all probands, including two recurrent de novo mutations (ACTB p.Arg196His and ACTG1 p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover the genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actins in development, and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutations of these two genes.

Baraitser–Winter syndrome: An additional Arab patient

An Arab child is presented herein with a phenotype that fits the rare Baraitser–Winter syndrome. Her clinical features included a unilateral iris coloboma, ptosis, hypertelorism, epicanthic folds, broad nasal bridge, full cheeks, pointed chin, low set abnormal ears and short neck. In addition, she had cardiac defect, previously undescribed brain anomaly, seizures, hypotonia and developmental delay. Chromosomal analysis of the peripheral lymphocytes and FISH study revealed a normal 46, XX karyotype. To date, Baraitser–Winter syndrome has only been reported in 19 patients of different ethnic families. The present case adds a new finding to the spectrum of malformations published before.

A case of Baraitser–Winter syndrome with unusual brain MRI findings: Pachygyria, subcortical-band heterotopia, and periventricular heterotopia

Baraitser–Winter syndrome (BaWS) is characterized by iris coloboma, ptosis, hypertelorism, and mental retardation; it is a rare multiple congenital anomaly or a mental-retardation syndrome of unknown etiology. Patients suffering from this syndrome have been also found to show brain anomalies such as pachygyria, subcortical-band heterotopia (SBH), and hippocampal malformations; therefore, these anomalies have been included in the phenotypic spectrum of this syndrome. We report the case of a Japanese boy suffering from BaWS; the patient’s brain magnetic resonance imaging scan revealed pachygyria, SBH, and periventricular heterotopia. However, the results of the genome-wide array comparative genomic hybridization did not reveal any chromosomal rearrangements.

The Phenotypic Spectrum of Baraitser-Winter Syndrome: A New Case and Review of Literature

The syndrome of iris coloboma, ptosis, hypertelorism, and mental retardation (Online Mendelian Inheritance in Man -- OMIM # 243310), also known as the Baraitser-Winter syndrome, originally was described in a brother and sister and in an unrelated girl in 1988. Six additional individuals with a similar phenotype have been reported in the world literature. Microphthalmos, microcornea, and brain malformations were added to the phenotypic spectrum of this syndrome in 1995. We report a child who presented with the aforementioned findings. Eye examination revealed bilateral microphthalmos and typical iris, optic nerve, and choroidal colobomas. Magnetic resonance imaging of the brain demonstrated pachygyria and cortical atrophy.

Orodigitofacial dysostosis and oculodentodigital dysplasia: Two distinct syndromes with some similarities: By Eliecer Eidelman and Mark L. Wagner. Oral Surg., Oral Med. & Oral Path. 23: 311–319, March, 1967

Baraitser–Winter syndrome (BRWS) is a malformation syndrome, characterized by facial dysmorphism, ocular colobomata, pachygyria, and intellectual defects.A 3.5 year old female child with BRWS has bilateral congenital ptosis, microcornea, iris, choroid, and optic nerve coloboma, retinal detachment, and mental retardation. She has also frontal bossing, prominent forehead, thick eyebrows, transverse slanting, hypertelorism, wide palpebral fissures, and nystagmus. The nose is broad, and bulbous with wide nares, and broad nasal tip. She has also low set posteriorly rotated ears, full cheeks, long philtrum, large mouth (macrostomia), gum hypertrophy, decayed teeth, high arched palate, pointed chin, short neck, low posterior hair line, partial left simian crease, and short fingers. MRI brain shows frontal polymicrogyria.This patient represents a mild case of Baraitser–Winter syndrome.