Nicolaides-Baraitser Syndrome with a Pathogenic de novo Variant in the SMARCA2 Gene: A Case Report

Abstract

Introduction: Nicolaides-Baraitser Syndrome (NCBS) (OMIM #601358) is a rare disorder, with a prevalence of less than 1 in 1,000,000 individuals. It is characterized by developmental delay, intellectual disability, early-onset epilepsy, sparse hair, and distinctive facial features. Diagnosis is established when a pathogenic heterozygous variant in the SMARCA2 gene is identified in an individual with a suggestive phenotype.

Case Report: We present the case of a teenager with a history of parental consanguinity, referred from neonatology due to microcephaly, mild generalized hypotonia, hirsutism, and synophrys. Chromosomal and structural abnormalities were ruled out, and the patient continued to be monitored. Subsequent assessments revealed developmental delay, moderate intellectual disability, low weight and height for age, and sparse hair. A clinical exome trio analysis was ordered, which identified a heterozygous pathogenic variant, c.3476G>A, in the SMARCA2 gene, leading to the diagnosis of NCBS.

Discussion: To date, fewer than 100 cases of NCBS have been described worldwide. This is the second reported case in Colombia and Latin America, with the patient exhibiting most typical disease manifestations, except epilepsy, despite the variant's association with an increased risk of epilepsy.

Conclusions: Given the low prevalence of the clinical syndrome and its association with epilepsy, it is important to have clinical suspicion that allows for accurate diagnosis and appropriate monitoring, particularly for the onset of epileptic seizures.