Paraganglioma and childhood-onset optic atrophy in a SDHA compound heterozygous patient: an example of dual dominant and recessive inheritance.
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SDHA pathogenic variants cause moderate to severe complex II deficiency, which manifests as a mitochondrial disorder in a homozygous/compound heterozygous child, or as hereditary cancer, mostly paraganglioma or pheochromocytoma, in a heterozygous adult. Here, we report the first composite heterozygous SDHA patient (hypomorphic allele p.(Thr508Ile) × null allele p.(Arg451His)) who developed complete congenital optic atrophy and a paraganglioma at the age of 36 yrs. No other germline variants were identified by sequencing panels of genes involved in these two disorders. This raises the question of whether paraganglioma screening should be implemented for carriers of a null SDHA variant.