Identification and characterisation of a novel homozygous KDM5A variant associated with severe axial hypotonia, seizures, and cardiac anomalies.
Serdar Bozlak, Cuneyd Yavas, Yusuf Seflekci et al.
✦ AI-curated · Sources linked
Case in brief
A patient with severe neurodevelopmental delay had neuromotor delay, profound axial hypotonia with absent head control, mild upper-limb spasticity, a history of seizures, facial dysmorphism and congenital heart disease. Exome sequencing identified a novel homozygous KDM5A c.2836 C > T p.(Gln946Ter) variant. KDM5A mRNA expression was reduced, but the decrease was not statistically significant. The findings supported El Hayek-Chahrour neurodevelopmental disorder and broadened its reported clinical spectrum to include severe motor impairment and complex cardiac involvement.
What made this case unusual
The cardiac findings included a major aortopulmonary collateral artery, described as previously undescribed in this condition. The authors also noted that reduced KDM5A expression was not statistically significant, raising the possibility that pathogenicity involves altered protein function rather than transcript depletion.
Diagnostic / clinical pearl
In a patient with severe neurodevelopmental impairment and congenital heart disease, exome sequencing can identify a biallelic KDM5A variant and help delineate the syndrome’s clinical spectrum.