Aliases: CHARGE association; Coloboma, Heart, Choanal Atresia, Retardation, Genital, and Ear Anomalies.
Gene(s) involved: CHD7: Chromodomain helicase DNA binding protein 7, at 8q12.2
Brief description of disorder: CHARGE syndrome is a widely variant syndrome presenting with common findings: ocular coloboma (>80%), heart anomalies, choanal atresia (>50%), developmental and/or growth retardation, genital anomalies, and ear anomalies or hearing loss (>90%). Facial palsy (40%), auditory nerve hypoplasty, dysphagia and aspiration (>70%), and/ or hyposmia or anosmia are other associated major findings in CHARGE.
Minor findings include developmental delay (~100%); heart defects (75-85%); growth retardation postnatally (~70%); cleft lip/palate (15-20%); genital hypoplasia (75%); characteristic facies inclusive of a prominent nasal bridge, flattened midface, broad, prominent forehead, and square-shaped face (70-80%); and tracheoesophageal defects (15-20%).
Clinical diagnosis of CHARGE syndrome is indicated for individuals presenting with all four major findings OR with three major and three minor findings. Probable or possible CHARGE is indicated for individuals with at least one major finding and some of the minor findings.
Occasional associated findings include protruding jaw, limb and bone abnormalities, clinodactyly, polydactyly, scoliosis, gastroesophageal reflux, chronic sinusitis, feeding difficulties, webbed neck, palmar crease anomalies, and behavioral characteristics, such as ADHD, autistic-like behaviors, obsessive-compulsive disorder, and aggressive behaviors.
CHARGE has a penetrance rate of 100%, thus heterozygous individuals will manifest signs and symptoms of this disorder. It is important to note that due to the variability of presentation, family members may not directly report any history consistent with CHARGE.
The prevalence of CHARGE syndrome is estimated to be between 1 in every 8,500 to 10,000 births.
Inheritance pattern: CHARGE syndrome results from a de novo genetic change in most instances. There have been documented cases of CHARGE being transmitted in an autosomal dominant fashion.
Genetics: CHARGE is caused by mutations in the CHD7 gene at 8q12.2. Affected individuals have a detectable CHD7 mutation in at least 60% of the cases. Missense, nonsense, frameshift, stop codons, microdeletions, duplications, deletions, translocations, and insertions are all mechanisms resultant in CHARGE. Cytogenetic chromosome analysis is recommended due to the occasional occurrence of chromosomal aberrations.
Test method: Conventional G-banded cytogenetic analysis, FISH, and aCGH can be used to detect deletions and duplications. Mutation analysis is not available at this lab.
Test sensitivity: Cytogenetic analysis detects approximately 25% of deletions that are greater than 5 Mb. FISH and aCGH will detect 98-100% of deletions/ duplications that are greater than 100 kb; however deletions/ duplications that are smaller than 100kb will not be detected by aCGH and deletions/ duplications that are smaller than the FISH probe will not be detected by FISH.
Specimen requirements for Cytogenetic Analysis, FISH, and Array:
Adult: 3-5 ml peripheral blood in a sodium-heparin tube.
Newborn: 1-3 ml blood in a sodium-heparin tube.
Turn-around-time:
Newborns: 2-3 days
Non-STAT: 2-14 days
FISH: 6-8 days
Array: 7-14 days
References:
GeneReviews
Jones KL (2006). CHARGE Syndrome. In K.L. Jones (6th Edition), Smith’s Recognizable Patterns of Human Malformation (pp. 276-277). Philadelphia: Elsevier.
revised 5-24-2011
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