SUN-759 - Phenotypic Variability in HDR (Barakat) Syndrome: Two GATA3-Mutation Cases Emphasizing the Need for Early Surveillance

HDR (Hypoparathyroidism, Sensorineural Deafness, Renal Anomalies) syndrome, or Barakat syndrome, is a rare autosomal dominant disorder caused by pathogenic variants in the GATA3 gene and demonstrates wide phenotypic variability across affected individuals and families. We present two adults with hypoparathyroidism and confirmed GATA3 variants who exhibited divergent extra-parathyroid manifestations, underscoring the importance of early recognition, genetic evaluation, and longitudinal surveillance.
Case 1 is a 60-year-old woman diagnosed with hypoparathyroidism at age 28 following a generalized tonic–clonic seizure two months postpartum. She reported longstanding paresthesias and sensorineural hearing loss and had a family history notable for paternal hearing loss. Genetic testing revealed a GATA3 variant of uncertain significance. She had no structural renal anomalies but demonstrated progressive chronic kidney disease over time (eGFR 45 mL/min/1.73 m²). She remains clinically stable on calcitriol with dietary phosphate restriction.
Case 2 is a 28-year-old man who presented with symptomatic hypocalcemia, muscle cramps, and carpopedal spasm. Laboratory evaluation showed severe hypocalcemia with inappropriately low PTH and vitamin D deficiency. He was found to have bilateral sensorineural hearing loss and a strong family history of hypocalcemia, hearing loss, and unilateral renal agenesis. Genetic testing identified a heterozygous pathogenic GATA3 frameshift variant (c.708dup; p.Ser237Glnfs*67), confirming autosomal dominant HDR syndrome.
These cases illustrate intrafamilial and interindividual heterogeneity in HDR syndrome, ranging from isolated endocrine disease to more complete syndromic involvement. Even patients lacking renal or auditory abnormalities at presentation may develop late complications. Clinicians should maintain a high index of suspicion for HDR syndrome in individuals with unexplained hypoparathyroidism, particularly when accompanied by hearing loss or suggestive family history. We emphasize the importance of genetic testing, cascade family screening, and structured surveillance including periodic audiometry, renal assessment, and biochemical monitoring to enable anticipatory management and reduce long-term morbidity.

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