Barakat syndrome

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Barakat syndrome, also known as HDR syndrome, was first described by Dr Amin Barakat et al in 1977. It is a genetic developmental disorder 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, pevicalyceal deformity, vesicoureteral reflux, chronic kidney disease, hematuria, proteinuria and renal scarring. The frequency is unknown, but the disease is considered to be very rare.

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 appear to be the underlying cause of this syndrome. 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. 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.

References

#Barakat, AY, D'Albora, JB, Martin, MM, Jose, PA. Familial nephrosis, nerve deafness, and hypoparathyroidism. J. Pediat 1977; 91: 61-4.
#Bilous, RW, Murty, G, Parkinson, DB, Thakker, RV, Coulthard, MG, Burn, J, Mathias, D, Kendall-Taylor, P. Brief report: Autosomal dominant familial hypoparathyroidism, sensorineural deafness, and renal dysplasia. New Eng J Med 1992; 327: 1069-74.
#Online Mendelian Inheritance in Man, Johns Hopkins University
#Hasegawa,T, Hasegawa, Y, Aso, T.; Koto, S, Nagai, T, Tsuchiya, Y, Kim, K, Ohashi, H, Wakui, K, Fukushima, Y. HDR syndrome (hypoparathyroidism, sensorineural deafness, renal dysplasia) associated with del(10)(p13). Am J Med Genet 1997; 73: 416-8.
#Fujimoto, S, Yokochi, K, Morikawa, H, Nakano, M, Shibata, H, Togari, H, Wada, Y. Recurrent cerebral infarctions and del (10) (p14p15.1) de novo in HDR (hypoparathyroidism, sensorineural deafness, renal dysplasia) syndrome. Am J Med Gene 1999; 86: 427-9.
#Nesbit MA, Bowl MR, Harding B, Ali A, Ayala A, Crowe C, Dobbie A, Hampson G, Holdaway I, Levine MA, McWilliams R, Rigden S, Sampson J, Williams AJ, Thakker RV. Characterization of GATA3 mutations in the hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome. J Biol Chem 2004; 279: 22624-34.
#Zahirieh A, Nesbit AM, Ali A, Wang K, He N, Stangou M, Bamichas G, Sombolos, K, Thakker RV, Pei Y. Functional analysis of a vovel GATA3 mutation in a family with the hypoparathyroidism, deaness and renal dysplasia (HDR) syndrome. J Clin Endocrinol Metab 2005; 4: 2445-50.
#Engel, JD, Professor and Chair, Dept. Cell & Developmental BiologyUniversity of Michigan, personal communication, 2008.

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