First report of an inherited MYCBP2 neurodevelopmental disorder: review of proband and parent presentation

TL;DR

This paper reports the first inherited case of a MYCBP2-related neurodevelopmental disorder, showing how it affects two generations.

Contribution

The first documented inherited case of a MYCBP2 neurodevelopmental disorder is presented, highlighting intergenerational variability.

Findings

A proband with a maternally inherited MYCBP2 variant showed significant developmental delays.

The proband’s mother exhibited subtle executive inefficiency but generally intact cognition.

Assessing parental genotype and phenotype can help predict developmental outcomes in inherited disorders.

Abstract

MYCBP2-associated neurodevelopmental disorder is an autosomal dominant genetic disorder, previously described with de novo variants. We present the case of a two-generation review of a proband with a maternally inherited heterozygous pathogenic variant in MYCBP2, c.4409dup (p.Leu1470Phefs*7). Neuropsychology assessment indicated developmental delays with proband’s scores falling well below age-level expectations, while proband’s mother demonstrated generally intact cognition with evidence of subtle executive inefficiency. Assessment of parental genotype and phenotype can help to anticipate child’s developmental trajectory, especially in genetic disorders associated with highly variable expressivity. However information gaps on familial impact of inherited neurodevelopmental disorders across generations remain.

Figures