HDR syndrome is defined by the triad of hypoparathyroidism, sensorineural deafness and renal disease. There are cases where individuals do not have all of the symptoms, and also cases where individuals have all three symptoms without an identified mutation.
Most patients with HDR syndrome have hypoparathyroidism and may present with congenital anomalies of the kidney and urinary tract (CAKUT) detected on routine prenatal ultrasound, hearing loss diagnosed by routine neonatal hearing screen, or other signs and symptoms of hypocalcemia (non-febrile seizures, tetany, myalgia, neuromuscular irritability). Moderate to severe sensorineural hearing loss is the most consistent feature of the syndrome, affecting almost all individuals. Many have renal issues, including but not limited to nephrotic syndrome, hematuria, proteinuria, proximal and distal renal tubular acidosis, and chronic kidney disease; GATA3 has been shown to be involved in kidney development.
This syndrome can be clinically diagnosed in patients who have all three components, and those who have two components with a positive family history; GATA3 testing is not necessary for the diagnosis in this group of patients. Individuals with isolated non-neurogenic sensorineural deafness and those with isolated renal disease should be suspected of having the syndrome, especially in the presence of a family history of any of the other components of the syndrome. In these instances, confirmatory GATA3 testing is necessary to confirm the diagnosis.
In patients with isolated hypoparathyroidism where sensorineural deafness and renal disease have been conclusively ruled out, no GATA3 studies are needed, as none of these patients had shown GATA3 haploinsufficiency.
GATA3