First described by Barakat et al. in 1977, Hypoparathyroidism, Sensory Neural Deafness, and Renal Disease, known as “HDR” or “Barakat” syndrome (OMIM 146255), is a clinically heterogeneous, rare autosomal dominant genetic disorder characterized by the triad of Hypoparathyroidism (H), sensorineural Deafness (D), and Renal disease (R). In the majority of cases, the syndrome is caused by deletions or mutation in the zinc-finger transcription factor GATA3 (OMIM 131320) on chromosome 10p14. All pedigrees seem to follow an autosomal dominant pattern with incomplete penetrance and variable expression. The syndrome is considered rare; however, it is probably more common than previously reported, as many patients might have been missed or unreported. Around 64% of reported cases had the full spectrum of HDR. It is possible that some findings could have been overlooked in some of the reported patients or could have appeared later on in life, but it is evident that this syndrome is genotypically heterogeneous. In an extensive review of the literature in 2018, Barakat et al. found a total of 180 cases. Original reports described the syndrome to consist of the triad of “H”, “D”, and “R”; however, subsequent reports described cases with variable expression of this phenotype with equal prevalence across ethnic groups, genders, and ages of diagnosis (from newborns to 60 years of age).
GATA3