Barakat syndrome
| Barakat syndrome | |
|---|---|
| Specialty | Medical genetics  |
Barakat syndrome, is a rare disease characterized by hypoparathyroidism, sensorineural deafness and renal disease, and hence also known as HDR syndrome. It was first described by Amin J. Barakat et al. in 1977.[1]
Presentation
It is a genetic developmental disorder[2] with clinical diversity characterized by hypoparathyroidism, sensorineural deafness and renal disease. Patients usually present with hypocalcaemia, tetany, or afebrile convulsions at any age. Hearing loss is usually bilateral and may range from mild to profound impairment. Renal disease includes nephrotic syndrome, cystic kidney, renal dysplasia, hypoplasia or aplasia, pelvicalyceal deformity, vesicoureteral reflux, chronic kidney disease, hematuria, proteinuria and renal scarring.
Genetics
The defect in the majority of cases has mapped to chromosome 10p (Gene Map Locus: 10pter-p13 or 10p14-p15.1). Haploinsufficiency (deletions) of zinc-finger transcription factor GATA3 or mutations in the GATA3 gene[3] appear to be the underlying cause of this syndrome. It causes the failure in the specification of prosensory domain and subsequently leads to increased cell death in the cochlear duct thus causing deafness.[4] Since the spectrum of phenotypic variation in affected patients is quite large, Barakat (HDR) syndrome probably arises as a low penetrance haploinsufficient disorder in which the patients' genetic background plays a major role in the severity of the disease.
Inheritance is probably autosomal dominant.
Diagnosis
A thorough diagnosis should be performed on every affected individual, and siblings should be studied for deafness, parathyroid and renal disease. The syndrome should be considered in infants who have been diagnosed prenatally with a chromosome 10p defect, and those who have been diagnosed with well defined phenotypes of urinary tract abnormalities. Management consists of treating the clinical abnormalities at the time of presentation. Prognosis depends on the severity of the kidney disease.
Epidemiology
The frequency is unknown, but the disease is considered to be very rare.[5]
References
- ^ Barakat AY, D'Albora JB, Martin MM, Jose PA (July 1977). "Familial nephrosis, nerve deafness, and hypoparathyroidism". J. Pediatr. 91 (1): 61–4. doi:10.1016/S0022-3476(77)80445-9. PMID 874665.
- ^ William B. Coleman (9 February 2010). Essential Concepts in Molecular Pathology. Academic Press. pp. 297–. ISBN 978-0-12-374418-0. Retrieved 5 December 2010.
- ^ Bernardini L, Sinibaldi L, Capalbo A, et al. (July 2009). "HDR (Hypoparathyroidism, Deafness, Renal dysplasia) syndrome associated to GATA3 gene duplication". Clin. Genet. 76 (1): 117–9. doi:10.1111/j.1399-0004.2009.01170.x. PMID 19659764.
- ^ Luo, X.-j.; Deng, M.; Xie, X.; Huang, L.; Wang, H.; Jiang, L.; Liang, G.; Hu, F.; Tieu, R.; Chen, R.; Gan, L. (10 May 2013). "GATA3 controls the specification of prosensory domain and neuronal survival in the mouse cochlea". Human Molecular Genetics. 22 (18): 3609–3623. doi:10.1093/hmg/ddt212. PMID 23666531.
- ^ Ranjbar-Omrani, G; Zamiri, N; Sabayan, B; Mohammadzadeh, A (May 2008). "Concomitant hypoparathyroidism, sensorineural deafness, and renal agenesis: a case of Barakat syndrome". Archives of Iranian medicine. 11 (3): 337–40. PMID 18426329.
External links
- Gaynor KU, Grigorieva IV, Nesbit MA, et al. (October 2009). "A missense GATA3 mutation, Thr272Ile, causes the hypoparathyroidism, deafness, and renal dysplasia syndrome". J. Clin. Endocrinol. Metab. 94 (10): 3897–904. doi:10.1210/jc.2009-0717. PMID 19723756.[permanent dead link]