Allan-Herndon-Dudley syndrome associated with SLC16A2 c.1384G>A (p.Gly462Arg): A family case report with retrospective molecular diagnosis in a deceased sibling.
Liwei Li, Jiarui Li, Zhenyan Li et al.
✦ AI-curated · Sources linked
Case in brief
A boy evaluated at 4.3 years had profound developmental delay, abnormal tone, dystonia, muscle atrophy, contractures, and bilateral cryptorchidism. Thyroid tests showed elevated T3, low T4, and mildly elevated thyroid-stimulating hormone; brain MRI showed delayed myelination, a thin corpus callosum, and widened frontal subarachnoid spaces. Sequencing identified hemizygous SLC16A2 c.1384G>A (p.Gly462Arg), with the variant confirmed in his heterozygous mother. The same variant was found in an archived neonatal blood spot from his deceased maternal half brother, who had severe developmental delay. At age 5, the proband remained unable to sit, stand, or walk independently.
What made this case unusual
Archived neonatal dried blood spot testing retrospectively confirmed the same SLC16A2 variant in a deceased maternal half brother, extending molecular diagnosis within the family despite the absence of his thyroid and neuroimaging records.
Diagnostic / clinical pearl
In a boy with unexplained severe neurodevelopmental impairment, the combination of high T3 and low T4 should prompt consideration of SLC16A2-related Allan-Herndon-Dudley syndrome.
Why it matters
Molecular testing of archived neonatal blood spots can establish a diagnosis in a deceased relative and provide additional information for family genetic counseling.