Clinical manifestations of Armfield syndrome in females with heterozygous FAM50A variants and skewed X-chromosome inactivation.
Francisco Javier Cotrina-Vinagre, Emma Soengas-Gonda, Juan F Quesada-Espinosa et al.
✦ AI-curated · Sources linked
Case in brief
A Spanish female patient presented with macrocephaly, global developmental delay, and leukoencephalopathy. Whole-exome sequencing identified a novel de novo heterozygous FAM50A variant, c.905 A > T (p.His302Leu). RNA expression analysis showed preferential expression of the variant from the paternal allele, associated with skewed X-chromosome inactivation. The report also identified an unrelated female with MRXSA and a different novel heterozygous FAM50A variant, c.866G > A (p.Arg289Gln).
What made this case unusual
Leukoencephalopathy was described as a previously unrecognized feature associated with FAM50A-related MRXSA; in the Spanish patient, skewed X-chromosome inactivation was identified as a potential pathogenic mechanism.
Diagnostic / clinical pearl
Consider FAM50A-related MRXSA in females with developmental delay and compatible findings; RNA expression analysis can help assess the significance of a heterozygous variant and skewed X-chromosome inactivation.
Why it matters
The reported cases broaden the described clinical and potentially neuroradiological spectrum associated with FAM50A variants.