Childhood onset dystonia, chorea or related movement disorder

Gene: HMBS

Red List (low evidence)

Biallelic inheritance of HMBS pathogenic variants is very rare. PMID: 14262853 De Villeneuve, 1577472 Llewellyn, 15534187 Solis, 14970743 Hessels and 31153822 Dixon. It has been reported in six children (5 families) five children with severe progressive neurological disease only one of these children has been reported to have dystonia.
PMID: 15534187 Solis reported a 28 month old patient with homozygous HMBS variants c.499C>T, p.(Arg167Trp) and who was shown to have approximately 1% of normal hydroxymethylbilane synthase activity, elevated porphyrins and porphyrin precursors, severe psychomotor delay, and central and peripheral neurologic manifestations. Neurologic examination confirmed psychomotor delay and revealed occasional dystonic head positioning and dystonic arm movements, normal appendicular muscle tone and strength, but axial hypotonia, reduced tendon reflexes, and bilateral Babinski responses.
Careful consideration should be given to the reporting of a single pathogenic variant as an incidental finding in the HMBS gene, due to its low clinical penetrance.

Created: 4 Apr 2025, 4:06 p.m. | Last Modified: 4 Apr 2025, 4:06 p.m.

Panel Version: 6.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 14262853
• 1577472
• 15534187
• 14970743
• 31153822
• 15534187

Red List (low evidence)