CHARGE syndrome is a constellation
of congenital malformations. The name of the condition
is an acronym of some of the
most common features:
C = Coloboma of the eye and Cranial
H = Heart malformation,
A = Choanal Atresia (blockage of the nasal passageways),
R = Retardation of growth after birth
and Retardation of development,
G = Genital hypoplasia (underdevelopment) in males
and urinary tract malformations,
E = Ear malformations and/or deafness.
In addition, there may be cleft lip or palate;
small chin; facial palsy; and esophageal atresia.
Other problems reported in children with CHARGE syndrome
include abnormally small head,
drooping of the eyelids, trouble breathing (due to
the choanal atresia), feeding problems in infancy, omphalocele,
anal stenosis or blockage, and
deficiency of growth hormone. Children with CHARGE
syndrome may die in the newborn period or later in
childhood. Children who survive usually show some degree
of mental deficiency. The range of the mental handicap
Most children with CHARGE syndrome have no family
history of the disorder.Very few people with CHARGE will have 100% of its known features.
Kallmann syndrome (KS) is characterized by hypogonadotropic hypogonadism and impaired sense of smell as the result of deficient hypothalamic gonadotropin-releasing hormone and agenesis of the olfactory lobes. Additional features include unilateral failure of kidney development; abnormalities in tooth development; cleft lip and/or palate; and bimanual synkinesis, which is manifested by involuntary movements of one hand that mimic the other hand.
Mutations on the CHD7 gene (located on Chromosome 8) have been identified in patients with CHARGE syndrome. About 30 CHD7 pathogenic variants have been reported in patients with Kallmann syndrome; they account for ~ 11% of patients with a clinical diagnosis.
Over 150 pathogenic variants in the ANOS1 gene have been reported in patients with Kallmann syndrome. The majority of these variants are truncating (HGMD). They account for ~ 8% of all KS cases. Large deletions have been reported in up to 25% of X-linked KS patients analyzed. Female carriers of ANOS1 pathogenic variants are usually not affected.
Pathogenic variants in the SEMA3E gene appear to be a rare cause of CHARGE or Kallmann syndromes. To date, only one patient with CHARGE syndrome was reported to have a pathogenic missense variant in SEMA3E. A different missense variant was reported in one patient with Kallmann syndrome.
Genes: ANOS1, CHD7, SEMA3E
Disorders: CHARGE Association, Kallman Syndrome 1, Kallman syndrome 5
Methodology: Next-Generation Sequencing
Purpose: Confirmation of Clinical Diagnosis
Test Requisition: Sequencing Requisition
Specimen Requirements: 2-5 mL Blood- Lavender Top Tube
CPT Codes: 81406,81407,81479 Cost: $1400.00 (Oklahoma Medicaid requires preauthorization for this test)
Turn-around-time: 5-6 weeks
1. Pagon RA, Graham JM, Zonana J, Yong SL (1981). "Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association". J. Pediatr. 99 (2): 223–7.
2. Hall BD (1979). "Choanal atresia and associated multiple anomalies". J. Pediatr. 95 (3): 395–8.
3. Vissers, L. E., van Ravenswaaij, C. M., Admiraal, R., Hurst, J. A., de Vries, B. B., Janssen, I. M., et al. (2004). "Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.". Nature Genetics 36 (9): 955–957.
4. Zentner GE, Layman WS, Martin DM, Scacheri PC (2010). "Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome". Am J Med Genet A 152 (3): 674–686.
5. Janssen, N; Bergman, JE; Swertz, MA; Tranebjaerg, L; Lodahl, M; Schoots, J; Hofstra, RM; van Ravenswaaij-Arts, CM; Hoefsloot, LH (2012). "Mutation update on the CHD7 gene involved in CHARGE syndrome.". Human mutation 33 (8): 1149–1160.
6. Kaplan J.D. et al. 2010. American Journal of Medical Genetics. Part A. 152A: 2796-801. PubMed ID: 20949504
7. Marcos S. et al. 2014. The Journal of Clinical Endocrinology and Metabolism. 99: E2138-43. PubMed ID: 25077900
8. Dodé C., Hardelin J.P. 2009. European Journal of Human Genetics. 17: 139-46. PubMed ID: 18985070
9. Ahmadzadeh A. et al. 2015. International Journal of Molecular and Cellular Medicine. 4: 152-9. PubMed ID: 26629483
10. Oliveira L.M. et al. 2001. The Journal of Clinical Endocrinology and Metabolism. 86: 1532-8. PubMed ID: 11297579
11. Lalani S.R. et al. 2012. CHARGE Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301296