RESUMO
Mutations in genes involved in chromatin remodelling have been implicated in broad phenotypes of congenital abnormalities and neurodevelopment. However, limited genotype–phenotype correlations are available for some of the rarestgenetic disorders that affect chromatin regulation. We hereby describe a 12-year-old girl presented at birth with severe hypotonia, developmental delay, a mid-line capillary malformation and distinctive craniofacial features. During the natural history of her disease, the girl developed severe spasticity and drug-resistant seizures, leading to a diagnosis of Bohring–Opitz syndrome (BOS). We performed whole-exome sequencing (WES) and identified a de novo mutation in ASXL1 (c.2033dupG) which results in the introduction of a premature stop codon (p.R678fs*6). ASXL1 encodes a polycomb repressive complex protein implicated in chromatin regulation and de novo mutations are a known cause of BOS. Phenotypes with segmental craniofacial overgrowth associated to midline capillary malformations enlarge the clinical spectrum of BOS at onset and further expand the differential diagnosis in ASXL1 mutation carriers.
RESUMO
Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP), previously known as macrocephaly-cutis marmorata telangiectatica congenita and macrocephaly-capillary malformation syndrome, is a rare multiple-malformation syndrome that is characterized by progressive megalencephaly, capillary malformations of the midline face and body, or distal limb anomalies such as syndactyly. Herein, we report a female infant case that satisfies the recently proposed criteria of MCAP and describe the distinctive neuroradiological and morphological features. We have also reviewed recently published reports and the diagnostic criteria proposed by various authors in order to facilitate the clinical diagnosis of these children in pediatric neurology clinics.