Barakat syndrome
Rare genetic disorder with hypoparathyroidism, deafness, and kidney disease.
Barakat syndrome, also called HDR syndrome, is a rare genetic disorder defined by the combination of hypoparathyroidism, sensorineural deafness, and kidney disease. It was first documented in 1977 by Amin J. Barakat and colleagues. The condition follows an autosomal dominant inheritance pattern, though it shows incomplete penetrance and variable expressivity, meaning not everyone with the genetic change develops all features, and symptoms can differ widely.
The hallmark signs include hypoparathyroidism, sensorineural hearing loss, and renal abnormalities. Hearing loss typically appears in childhood or adolescence, is often bilateral, and can range from mild to profound. Affected individuals may present at any age with low calcium levels, muscle spasms (tetany), or seizures without fever. Kidney problems can include nephrotic syndrome, cystic kidneys, renal dysplasia, underdevelopment or absence of a kidney, pelvic or calyceal deformities, vesicoureteral reflux, chronic kidney disease, blood or protein in the urine, and kidney scarring. Other reported features include intellectual disability, polycystic ovaries, distinct facial characteristics, ischemic stroke, and retinitis pigmentosa.
Genetically, the syndrome is caused by a defect on chromosome 10p (specifically at 10pter-p13 or 10p14-p15.1). Most cases involve deletions or mutations in the GATA3 gene, which codes for a zinc-finger transcription factor. This haploinsufficiency disrupts the development of the inner ear’s sensory domain, leading to increased cell death in the cochlear duct and resulting deafness. Because the range of symptoms is so broad, Barakat syndrome is thought to be a low-penetrance haploinsufficient disorder, where an individual’s genetic background strongly influences disease severity.
Diagnosis requires a thorough evaluation of each affected person, and siblings should be screened for hearing loss, parathyroid issues, and kidney disease. The syndrome should be considered in infants with a prenatal diagnosis of a chromosome 10p defect or those with well-defined urinary tract abnormalities.
Treatment focuses on managing symptoms as they arise. This includes genetic counseling, correcting calcium levels, addressing hearing problems, monitoring kidney function, and keeping a close watch on any kidney cysts.
Prognosis depends largely on the severity of kidney disease.
- First described
- 1977
- Inheritance
- Autosomal dominant
- Gene locus
- 10pter-p13 or 10p14-p15.1
- Causative gene
- GATA3
- Reported cases
- 180 as of 2023
- Key features
- Hypoparathyroidism, sensorineural deafness, renal disease
Lore & Background
The syndrome is inherited as an autosomal dominant trait. The defect in most cases maps to chromosome 10p, and haploinsufficiency or mutations in the zinc-finger transcription factor GATA3 appear to be the underlying cause. This leads to failure in the specification of the prosensory domain and increased cell death in the cochlear duct, causing deafness. The spectrum of phenotypic variation is large, and the disorder likely arises as a low-penetrance haploinsufficient disorder where genetic background plays a major role in severity. Other reported features include intellectual disability, polycystic ovaries, distinct facial characteristics, ischemic stroke, and retinitis pigmentosa.
Reader's Guide
Barakat syndrome is significant as a rare genetic disorder that illustrates the pleiotropic effects of GATA3 haploinsufficiency, linking parathyroid, auditory, and renal development. Its variable expressivity and incomplete penetrance highlight the complexity of genotype-phenotype correlations. Diagnosis requires thorough evaluation of affected individuals and siblings for deafness, parathyroid, and renal disease, and should be considered in infants with chromosome 10p defects or urinary tract abnormalities. Management focuses on treating clinical abnormalities at presentation, including calcium correction, hearing treatment, kidney function monitoring, and cyst surveillance. Prognosis depends on kidney disease severity; life expectancy is unaffected if the disease is mild. With only 180 reported cases as of 2023, the syndrome remains very rare, and its frequency is unknown. The condition underscores the importance of genetic counseling and multidisciplinary care for affected families.
Did You Know?
- Around 65% of people with Barakat syndrome have all three features: hypoparathyroidism, sensorineural deafness, and kidney disease.
- The syndrome is caused by deletions or mutations in the GATA3 gene on chromosome 10p.
- Sensorineural deafness in Barakat syndrome typically presents in childhood or adolescence and is usually bilateral.
- As of 2023, only 180 cases have been documented in global medical literature.
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