DYT-AOPEP: A case series from India expanding the clinical and genetic spectrum

DYT-AOPEP (Aminopeptidase O) or DYT31 is a rare, newly discovered genetic cause of autosomal recessive monogenic adult-onset isolated dystonia. We describe three Indian patients with likely pathogenic variants in the AOPEP gene, expanding the clinicogenetic spectrum DYT-AOPEP.

First proband presented with adult-onset generalised isolated dystonia, which was medically refractory, but responded to GPi-DBS. He harboured a homozygous splice site variant (NM_001193329.3:c.1916+1G > C). The second proband had adult-onset isolated generalised dystonia without any family history, which started in her lower limb. She carried a homozygous stop-gain variant [NM_001193329.3:c.617dup; (p.Tyr206∗)]. The third proband had oromandibular dystonia progressing to generalised dystonia with a homozygous missense stop-gain variant [NM_001193329.3:c.895C > T; (p.Arg299∗)]in the AOPEP gene.

A total of eighteen patients have been described in the literature so far with variable age of onset, isolated limb-onset dystonia, or cervical dystonia, most characteristically retrocollis and is sometimes associated with parkinsonism. Some patients develop mixed hyperkinetic movement disorders. Pallidal deep-brain stimulation is a good therapeutic option in medically refractory cases.

AOPEP is a recently identified gene within the expanding spectrum of dystonia-associated genes. An increasing number of patients with pathogenic variants have been reported in recent studies, supporting its consideration for inclusion in dystonia gene panels and broader population-based screening.