Concerns regarding linear growth and dysmorphic features are common in several genetic syndromes. Among these, PTHLH-related brachydactyly type E (BDE), which is inherited in an autosomal dominant manner, is a rare but distinct genetic disorder. This condition is caused by heterozygous variants in the PTHLH gene, which encodes a parathyroid hormone-related protein, a key regulator of endochondral bone development. To date, very few cases of this condition have been reported. Here, we describe a case of a PTHLH gene variant (heterozygous for c.54C>G p.Tyr18Ter) in an Indian boy who presented with linear growth problems, BDE, and subtle dysmorphism. This case underscores the importance of genetic evaluation to clarify ambiguous clinical presentations and guide appropriate management strategies. This detailed phenotypic characterization of the early truncating PTHLH variant p.Tyr18Ter expands the clinical spectrum associated with PTHLH haploinsufficiency.
Hulse et al. (Thu,) studied this question.