Barakat syndrome
| Barakat syndrome | |
|---|---|
| Other names | HDR syndrome[1] |
 | |
| This condition is inherited in an autosomal dominant manner. | |
| 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 is an autosomal dominant condition with incomplete penetrance and variable expressivity[2] that was first described by Amin J. Barakat et al. in 1977.[3]
Signs and symptoms
[edit]It is a genetic developmental disorder[4] with clinical diversity characterized by hypoparathyroidism, sensorineural deafness and renal disease.[5] Sensorineural deafness typically presents in childhood or adolescence. Affected people usually present with hypocalcaemia, tetany, or afebrile convulsions at any age.[1] 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.[citation needed]
Other reported features include: intellectual disability, polycystic ovaries, particular distinct facial characteristics, ischaemic stroke and retinitis pigmentosa.[5]
Genetics
[edit]Barakat syndrome is a rare condition inherited as autosomal dominant trait.[5][6]
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[7] 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.[8]
Since the spectrum of phenotypic variation in affected people is quite large, Barakat syndrome probably arises as a low penetrance haploinsufficient disorder in which their genetic background plays a major role in the severity of the disease.[9][2]
Diagnosis
[edit]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.[citation needed]
Treatment
[edit]Management consists of treating the clinical abnormalities at the time of presentation and includes genetic counselling, correcting calcium, treating hearing problems, monitoring kidney function and close monitoring of cysts of the kidney.[1][5]
Prognosis
[edit]Prognosis depends on the severity of the kidney disease. Life expectancy is unaffected if the disease is mild.[1]
Epidemiology
[edit]The frequency is unknown, but the disease is considered to be very rare.[10] Both male and females have been noted to be affected by hypoparathyroidism, sensorineural deafness, and renal disease.[1] However, specific symptoms and severity can vary. Around 65% of people with Barakat syndrome have hypoparathyroidism, sensorineural deafness and kidney disease together.[5] As of 2023, the global medical literature has documented 180 reported cases.[11]
References
[edit]- ^ a b c d e "Hypoparathyroidism sensorineural deafness renal disease syndrome". www.orpha.net. Retrieved 29 March 2019.
- ^ a b Barakat, Amin J.; Raygada, Margarita; Rennert, Owen M. (2018-04-16). "Barakat syndrome revisited". American Journal of Medical Genetics Part A. 176 (6): 1341–1348. doi:10.1002/ajmg.a.38693. ISSN 1552-4825. PMID 29663634. S2CID 4898362.
- ^ 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.
- ^ a b c d e "Barakat syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. National Institutes of Health. 7 September 2018. Archived from the original on 12 November 2019. Retrieved 12 November 2019.
- ^ Ferraris, Silvio; Del monaco, Angelo Giovanni; Garelli, Emanuela; Carando, Adriana; De Vito, Barbara; Pappi, Patrizia; Lala, Roberto; Ponzone, Alberto (2009-03-24). "HDR syndrome: A novel "de novo" mutation in GATA3 gene". American Journal of Medical Genetics Part A. 149A (4): 770–775. doi:10.1002/ajmg.a.32689. ISSN 1552-4825. PMID 19248180. S2CID 30760817.
- ^ 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. S2CID 37338806.
- ^ 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. PMC 3749857. PMID 23666531.
- ^ Joseph, Anne D. D.; Sirisena, Nirmala D.; Kumanan, Thirunavukarasu; Sujanitha, Vathualan; Strelow, Veronika; Yamamoto, Raina; Wieczorek, Stefan; Dissanayake, Vajira H. W. (2019-10-28). "Hypoparathyroidism, Sensorineural deafness and renal disease (Barakat syndrome) caused by a reduced gene dosage in GATA3: a case report and review of literature". BMC Endocrine Disorders. 19 (1): 111. doi:10.1186/s12902-019-0438-4. ISSN 1472-6823. PMC 6816161. PMID 31660939.
- ^ 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.
- ^ Arciniegas Berkešová, Beáta; Borbély, Zoltán (2023-05-16). "Barakat syndrome". Vnitřní lékařství. 69 (3): E16–E19. doi:10.36290/vnl.2023.036. ISSN 0042-773X. PMID 37468331.
Further reading
[edit]- 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.