Rare Variant of PTH1R Mutation in an Indian Family

Introduction: Murk Jansen metaphyseal chondrodysplasia is an extremely rare form of skeletal dysplasia. It is caused by the mutation in PTH1R gene (1).

Materials: A 13 year old boy presented with history of progressive bowing of both legs since 5 years of age. He had no history of development delay, seizures, renal stones or abdominal distension. On examination, he was having prominent upper face, prominent tip of nose, long philtrum, small mandible and severe bowing of legs with deformed knee joint. His bone mineral profile came out to be normal. His skeletal survey showed severe metaphyseal dysplasia of long bones of lower limb. His genetic testing revealed heterozygous mutation in PTH1R gene, c.1562G>A variant in exon 16. On extended evaluation, his father and paternal grandmother were also having similar phenotype, however not as severely affected as the index case.

Result: Murk Jansen metaphyseal chondrodysplasia is characterized by severe short stature, short bowed limbs, clinodactyly and dysmorphic facies with metabolic derangement of hypercalcemia and hypophosphatemia (2). The variant present in our patient has not been reported anywhere yet, hence revealing a new molecular mechanism to an already known rare disease.

Conclusion: Molecular diagnosis of skeletal dysplasia is of paramount importance as they are a clinically heterogenous group with varied presentation with non-specific radiological findings, however with different treatment and prognostic implications. References Nampoothiri S, Fernández-Rebollo E, Yesodharan D, et al. Jansen metaphyseal chondrodysplasia due to heterozygous H223R PTH1R mutations with or without overt hypercalcemia. J Clin Endocrinol Metab 2016;101(11):4283-4289. Schipani E, Langman CB, Parfitt AM, et al. Constitutively activated receptors for parathyroid hormone and parathyroid hormone- related peptide in Jansen's metaphyseal chondrodysplasia. N Engl J Med 1996;335(10):708-714.