Missense Variant Met119Val in ACTB in a Patient with Baraitser-Winter Syndrome Type 1 and Mild Intellectual Disability

Abstract

Here we report on a Brazilian female patient with striking dysmorphic craniofacial features of the Baraitser-Winter syndrome (BRWS), including coarse face with prominent metopic ridge, highly arched eyebrows, ocular hypertelorism, ptosis, long palpebral fissures, broad nasal tip, long philtrum, full cheeks, cleft lip and palate, and low-set ears with abnormal lobe. Other clinical signs included partial agenesis of the corpus callosum, asymptomatic pineal cyst, oligodontia, cervical cystic hygroma, pterygium colli, axillary pterygium, duplicated left hallux and seizures. Sanger sequencing of the ACTB gene showed a heterozygous missense variation NM_001101.5 (ACTB):c.355A>G (p.Met119Val). This variant is located very close to the ACTB variant Thr120Ile, which results in the severe BRWS phenotype with severe intellectual disability and absence of speech, firstly described as Fryns-Aftimos syndrome. Despite this, our patient had mild developmental delay, without impairment of speech, and with moderated learning difficulties.