Reply to Herz et al. and Humphrey et al. : Genetic heterogeneity of cerebellar hypoplasia with quadrupedal locomotion

Abstract

Mutations in the very low-density lipoprotein receptor VLDLR are responsible for cerebellar hypoplasia with quadrupedal gait (1). The most likely mechanism leading to this phenotype is that VLDLR deficiency in the brain at a key stage of development precludes the normal formation of neural structures critical for gait. Quadrupedal gait is an integral part of VLDLR-associated cerebellar hypoplasia syndrome in these families (1, 2). It is not necessary to invoke an “epiphenomenon” or “unfavorable environmental conditions” to explain the phenotype (3), but rather simply considering clinical heterogeneity in the context of genomic understanding of complex traits is sufficient.