Unveiling HDR Syndrome in a 4-Year-Old Boy with Hypocalcemic Convulsions

Introduction
Hypocalcemic convulsions in young children is rarely due to congenital hypoparathyroidism (HP). HP, Sensorineural Deafness, and Renal Disease (HDR) syndrome was diagnosed in a toddler with hypocalcemic convulsions.
Clinical case
A 3.5-year-old boy presented with febrile seizures. His medical history was unremarkable, aside from prematurity and recurrent otitis media. His father had been diagnosed with idiopathic HP at the age of 10 years, while his deafness was attributed to recurrent otitis media during childhood. Physical examination showed mild micrognathia. Biological assessment showed a low serum calcium level (1.70 mmol/L) and elevated serum phosphorus (2,61 mmol/l). Hormonal analysis revealed a normal serum PTH (31.1 ng/L). A familial form of hypoparathyroidism was suspected and treatment with alphacalcidol was initiated. Renal ultrasound and hearing testing were normal. A CGH-array and CaSR gene sequencing showed no abnormalities. Additional next-generation DNA sequencing at the of 5.9 years, when a 40 dB bilateral hearing loss was observed, identified a heterozygous, paternally inherited pathogenic variant in the GATA3 gene (NM 001002295.2 (GATA3): c. 123C>G), confirming the diagnosis of HDR syndrome.
Discussion
HDR syndrome (MIM #146255) is a rare autosomal dominant disorder, characterized by HP, sensorineural deafness, and renal dysplasia, is caused by loss-of-function variants in the GATA3 gene. Clinical presentation is very heterogenous. Median age of HP onset is 11 years. Deafness in general occurs earlier and is typically bilateral and more pronounced at higher frequencies.
Conclusion
HP should be suspected when hypocalcemia is accompanied by hyperphosphatemia, even if serum PTH levels are (inappropriately) normal. HDR syndrome should be included in the differential diagnosis of a familial HP, even in the absence of renal dysplasia or hearing loss. Early diagnosis of HDR syndrome enables timely detection and treatment of hearing loss and renal insufficiency if renal dysplasia is present.