ESPE Abstracts

Aim: We present a case with clinical manifestations of HDR (hypoparathyroidism, sensorineural deafness, and renal dysplasia) syndrome resulting from a missense variant in the GATA3 gene, which is not yet reported in the patients defined in the literature to our knowledge.

Case presentation: A 13-year-old male patient, presented to the emergency department with a suspected seizure history. He reportedly woke up during the night screaming, followed by generalized body stiffening and teeth clenching. There was no history of convulsions previously, nor signs of fever or infection. It was learned that the 49-year-old mother's third pregnancy resulted in a birth at 39 weeks, weighing 2300 grams. At the age of 6, during screening for nocturnal enuresis, a renal ultrasound revealed that the patient had a single kidney. Additionally, a diagnosis of bilateral hearing loss was made by a formal audiogram, and since then, the person has been using hearing aids. School performance ranged from below average to moderate. There was no history of hearing loss or kidney disease in any relatives. In the physical examination, the body weight was 43.9 kg (-0.8 SDS), the height was 164.1 cm (0.51 SDS), and the body mass index was 16.3 (-1.44 SDS). The patient was diagnosed with primary hypoparathyroidism, indicated by low parathyroid hormone levels despite the presence of hypocalcemia. In the urinary system ultrasonography, the right kidney was observed in a normal location, with a size of 121 mm, parenchymal thickness of 19-20 mm, and increased parenchymal echogenicity graded as 1. The left kidney was not visualized. The audiometer revealed bilateral moderate sensorineural hearing loss. Genetic testing was planned due to clinical suspicion of HDR syndrome. In the fourth exon of the GATA3 gene, c.784A>T (p.Arg262Trp) missense variant was detected in heterozygous state. It was not reported in ClinVar, LOVD or large population databases such as gnomAD, ExAC and TOPMed. In silico prediction tools like Revel, SIFT, Varity, AlphaMissense suggested that this variant had a disruptive effect on protein function. To our knowledge, c.784A>T variant was not reported before in individuals clinically diagnosed with HDR syndrome. However a different nucleotide change in the same genomic position, c.784A>G(p.Arg262Gly), was identified in a female patient with hypoparathyroidism, sensorineural deafness, but no renal anomalies (PMID: 21157112).

Conclusion: When encountering individuals with hypocalcemia and hypoparathyroidism, particularly those with a background of sensorineural deafness or renal disease, it is crucial to consider the possibility of HDR syndrome.