Суміжна патологія/ Concomitant pathology

Синдром Bardet-Biedl

Disease summary

Bardet-Biedl syndrome (BBS) is a rare, autosomal-recessive ciliopathy characterized by retinal dystrophy, obesity, renal abnormalities, and genital abnormalities, postaxial polydactyly and learning difficulties. To date, mutations in more than 20 different genes have been described as being responsible for BBS (ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CCDC28B, CEP290, IFT27, LZTFL1, MKKS, MKS1, SDCCAG8, TMEM67, TRIM32, TTC8, WDPCP) 1, 11.

Autosomal recessive, digenic recessive inheritance

 1/100,000-160,000 (Northern European and North American populations); 1/13,500 (Arab populations) 1, 2, 11.
 Primary clinical features for Bardet-Biedl syndrome include the following:
  • Rod-cone dystrophy, (>90% of cases)1
  • Postaxial polydactyly (21% of cases)1
  • Truncal obesity(72-92% of cases)1
  • Learning disabilities and cognitive impairment.
  • Hypogonadism (males) or genital abnormalities (in females)2
  • Renal anomalies (53-82% of cases) 3, 1, 11.

Secondary clinical features of Bardet-Biedl syndrome include the following1, 11:

  • Speech delay/disorder
  • Developmental delay
  • Behavioral abnormalities
  • Eye abnormalities (strabismus, cataracts, and astigmatism)
  • Brachydactyly/syndactyly
  • Ataxia/poor coordination/imbalance and mild hypertonia
  • Diabetes mellitus
  • Orodental abnormalities (dental crowding, hypodontia, small dental roots, and high-arched palate)
  • Cardiovascular anomalies5.
  • Hepatic involvement
  • Hirschsprung disease
  • Anosmia
 The diagnosis of Bardet-Biedl syndrome relies on clinical findings and family history.
  • Suggested criteria is the presence of:

            o    4 primary features or

            o    3 primary features + 2 secondary features

  • Diagnosis is confirmed by the identification of a pathogenic variant in one of the following genes: ARL6, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, CCDC28B, CEP290, IFT27, LZTFL1, MKKS, MKS1, SDCCAG8, TMEM67, TRIM32, TTC8, WDPCP.
 There is no cure for Bardet-Biedl syndrome to date, but treatment can relieve symptoms 11.
  • Visual aids and educational programs for the visually impaired.
  • Obesity is managed with diet, exercise, and behavioral therapies.
  • Speech therapy for speech delay/impairment.
  • Renal anomalies and hypertension are treated as in the general population.
  • Hydrocolpos, vaginal atresia, or hypospadias may be surgically corrected.
  • Hormone replacement therapy for hypogonadism.
  • Cardiac abnormalities are treated as in the general population.

 

References

  1. Forsythe E, Beales PL. Bardet-Biedl syndrome. Eur J Hum Genet. 2013;21:8–13.
  2. Deveault et al. BBS genotype-phenotype assessment of a multiethnic patient cohort calls for a revision of the disease definition. Hum Mutat. 2011;32:610–9.
  3. Imhoff et al. Bardet-Biedl syndrome: a study of the renal and cardiovascular phenotypes in a French cohort. Clin J Am Soc Nephrol. 2011;6:22–9.
  4. Beales et al. New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J Med Genet. 1999;36:437–46.
  5. Elbedour et al. Cardiac abnormalities in the Bardet-Biedl syndrome: echocardiographic studies of 22 patients. Am J Med Genet. 1994;52:164–9.
  6. Katsanis N. The oligogenic properties of Bardet-Biedl syndrome. Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R65-71. Epub 2004 Feb 19.
  7. Stoetzel et al. BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nat Genet. 2006;38:521–4.
  8. Nishimura et al. Comparative genomics and gene expression analysis identifies BBS9, a new Bardet-Biedl syndrome gene. Am J Hum Genet. 2005;77:1021–33.
  9. Stoetzel et al. Identification of a novel BBS gene (BBS12) Highlights the Major Role of a Vertebrate-Specific Branch of Chaperonin-Related proteins in Bardet-Biedl syndrome. Am J Hum Genet. 2007;80:1.
  10. Leitch et al-. Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nat Genet. 2008;40:443–8.
  11. Forsythe et al. Bardet-Biedl Syndrome. Pagon RA, Adam MP, Ardinger HH, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2017.

Джерело: https://www.centogene.com/science-education/centopedia/factsheets/ngs-panel-genetic-testing-for-bardet-biedl-syndrome.html

Також інформацію можна отримати на сайті: https://www.bardetbiedl.org/what-is-bbs/

відdr.shevchuk