A Homozygous PTRHD1 Missense Variant (p.Arg122Gln) in an Individual with Intellectual Disability, Generalized Epilepsy, and Juvenile Parkinsonism.

Biallelic variants in PTRHD1 have been linked to autosomal recessive intellectual disability, spasticity, and juvenile parkinsonism with only a limited number of patients reported so far. Here, we describe the clinical and genetic findings of another female individual of Austrian origin who also experienced infantile neurodevelopmental abnormalities, intellectual disability, and childhood-onset parkinsonian features, all of which are in concordance with the known phenotypic spectrum. In addition, she developed genetic generalized epilepsy around the age of 4 years, persisting into adulthood. Using diagnostic exome sequencing, we identified the homozygous missense variant c.365G>A, p.(Arg122Gln) in PTRHD1 (NM_001013663). In conclusion, we confirm previous reports suggesting an association between biallelic PTRHD1 variants and parkinsonism with neurodevelopmental abnormalities. Moreover, we hypothesize that generalized epilepsy may be part of the phenotypic spectrum.