Abstract
The Male-Specific Lethal 2 Homolog (MSL2) gene was recently reported to be responsible for a novel, rather severe neurodevelopmental syndrome including brain abnormalities. We report the first prenatal case of an MSL2-related pathology caused by a de novo MSL2 splice variant (c.142+1G>T). RNA study on amniotic fluid cells showed an intronic inclusion and frameshift, consistent with loss-of-function intolerance. The fetus, who presented with bilateral moderate ventriculomegaly, also carried a paternally inherited 15q13 microduplication. Brain MRI at 2 and 4 months of age showed stable, mildly enlarged lateral ventricles. Clinical evaluation at 11 months revealed only a mild developmental delay. This case illustrates the challenges in predicting the postnatal outcome of recently characterized syndromes with limited documented cases, especially in association with a second independent genetic anomaly. Follow-up will be crucial to better define the developmental impact of this first reported MSL2 splice mutation in combination with the 15q13 microduplication, and characterization of more patients with MSL2 mutations will contribute to expanding the phenotypic spectrum.