Molecular Genetics of Nail–Patella Syndrome

Abstract

Nail–patella Syndrome (NPS) is a pleiotropic disorder affecting development of the limbs, kidneys, eyes and central nervous system, which is the result of heterozygous, loss‐of‐function mutations in the transcription factor, LIM‐homeobox 1β (LMX1B). There is no correlation between the type or nature of individual mutations and the severity of the phenotype. The availability of animal models, together with analysis of gene expression patterns during development, has substantiated that the range of clinically relevant signs and symptoms is greater than appreciated previously. Evidence is building that attention deficit±hyperactivity disorder and depression may be constituent parts of the syndrome. The variation in the range and severity of symptoms, and the diverse range of affected tissues, make NPS an appropriate model in which to study the effects of gene interactions on the observed phenotype. Key Concepts: NPS is a pleiotropic, clinically variable autosomal dominant disorder. LMX1B is a member of a gene family primarily involved in regulating neuronal patterning. Loss of function mutations in LMX1B cause NPS but do not predict disease severity. Analysis of Lmx1b expression has helped explain previously unknown neural aspects of NPS. Physicians should be aware of the extra‐skeletal aspects of NPS and institute appropriate monitoring and treatment.