VPS13D: One Family, Same Mutations, Two Phenotypes

Abstract

Here, we report two siblings with compound heterozygous variants in VPS13D but a considerable divergent phenotype highlighting the difficulties of phenotype–genotype correlation in this rare disease. A 19-year-old patient presented to our outpatient department with a five-year history of progressive gait impairment. Motor and cognitive development during childhood was described as normal. The patient visited a regular school and was able to participate in physical education until the onset of symptoms. There were no known neurologic diseases in the Caucasian family, consisting of five sisters (II.1–3, II.5, and II.6), and the patient (II.4). However, one younger sister (II.6) of the patient suffered from developmental delay and intellectual disability without further physical impairment, and the oldest sister (II.1) living separate from the family was supposed to have “gait problems”. On examination, the patient presented with saccadic pursuit, gaze-evoked nystagmus, and mild hypophonia, accompanied by mild dysmetria of the lower limbs, spastic tetraparesis pronounced in the lower limbs (MRC 4), and a spastic ataxic gait with footdrop on the left (see Table 1 and Video 1).