O2149: Risk of Hip Displacement in Patients with Leukodystrophy by Genetic Diagnosis

Background: Leukodystrophies (LD) are a broad group of rare genetic disorders that result in the disruption or destruction of central myelination. Clinical characteristics vary both in severity and by the 50 identified subtypes. LD, in contrast to cerebral palsy (CP), is a progressive neuromuscular disorder. Neuromuscular hip displacement is a known complication in patients with LD, but patterns of hip migration and acetabular morphology by genetic variant of LD have not been described.

Methods: Patients with a known LD or progressive white matter disorder who were evaluated with x-rays of the hips/pelvis at a single large tertiary care pediatric hospital from 2010 onwards were included. All anteroposterior radiographs were measured for migration percentage (MP) and acetabular index (AI). The MP of each patient’s more severely displaced hip was utilized. A normal, reduced hip was considered by MP < 30 while a hip-at-risk was identified by 30< MP < 50. Furthermore, subluxed hips were defined by a MP 50≤MP≤80 with a break in Shenton’s line, and hips with a MP>80 were considered dislocated. An AI

Results: A total of 186 patients (78 female, 108 male) with a mean age of 6.48 ± 3.94 years at the most recent hip radiograph met inclusion criteria. A significant difference between LD type and hip classification (normal, hip-at-risk, subluxed, dislocated) (p < 0.001) and overall MP (p < 0.001) was demonstrated. Furthermore, a significant difference between LD type and both left and right AI were appreciated (p=0.037, 0.050 respectively). Post hoc analysis revealed significant pairwise differences which merit discussion. Aicardi-Goutières Syndrome (AGS), Pelizaeus-Merzbacher Disease (PMD), Metachromatic Leukodystrophy (MLD), and Krabbe Disease (KD) showed a significantly higher occurrence of hip migration than Adrenoleukodystrophy (ALD) (p=0.009, 0.049, 0.015, and 0.027 respectively). Similarly, AGS in comparison to Alexander Disease (AxD) demonstrated a higher incidence of more severe dysplasia (p=0.027) (Figure 1). No significant pairwise differences in AI were appreciated by genetic diagnosis.

Conclusion: This is the first reported series in the literature to date on the status of hips in patients with LD across several genetic variations. In contrast to CP, hip disease in LD seems to vary by genetic diagnosis. There appear to be diagnoses which have a greater propensity for hip disease and some which have less. As such, knowing the specific diagnosis in these cases becomes critically important for hip screening and consideration of interventions. Identified risk factors with respect to genetic variation can be used in the development of hip surveillance programs for early detection and management of hip migration in children with LD.