Introduction to CHARGE syndrome

CHARGE syndrome (OMIM 214800) is a variable multiple congenital anomaly syndrome. It occurs in approximately 1 in 15,000-17,000 newborns (Janssen et al. 2012).

CHARGE is an acronym that summarizes six cardinal clinical features of the syndrome:

• Coloboma of the eye (a closure defect of the iris and/or retina)
• Heart defect
• Atresia of choanae (a blocked passage of the nose to the throat)
• Retardation of growth and/or development
• Genital hypoplasia (e.g. a micropenis in boys and delayed puberty)
• Ear abnormalities often combined with deafness and balance problems due to semicircular canal abnormalities

Other clinical findings are: dysfunction of the cranial nerves (resulting in facial palsy ad swallowing problems), anosmia (inability to smell), renal abnormalities and cleft lip/palate.

In 2004 the CHD7 (Chromodomain Helicase DNA binding protein 7) gene was discovered to be the major gene involved in CHARGE syndrome. CHD7 mutations or deletions are found in over 90% of typical CHARGE patients (Vissers et al 2004).

However, the clinical CHARGE spectrum is broad and some individuals with a CHD7 mutation can be very mildly affected. Finding a CHD7 mutation has important implications for clinical surveillance and genetic counselling. We therefore drew up a guideline to help clinicians decide when to perform CHD7 analysis (Bergman et al. 2011). Ultimately the molecular diagnosis became part of the clinical criteria for CHARGE syndrome (Hale et al 2017).

The care for patients with typical CHARGE syndrome and all patients with a CHD7 mutation is usually complex. The follow-up should therefore ideally be done by a multidisciplinary team of experts. In the University Medical Centre Groningen, we hold a CHARGE outpatient clinic (EN)/  Expertisecentrum Uniek CHARGE syndroom (NL) in which several specialisms are involved.

We continuously try to improve the medical care for individuals with CHARGE syndrome as can be read in our paper on surveillance and in the overview that we wrote for Genereviews.

Research topics that we explored in the past

(for publications see “publications on CHARGE syndrome”)

• The clinical and pathogenetic overlap between CHARGE and Kallmann syndromes
• Smell and pubertal development in CHARGE syndrome
• Congenital heart defects in CHARGE syndrome
• The clinical overlap between CHARGE and 22q11.2 deletion syndrome
• Immunological problems in CHARGE syndrome
• Adrenal function in patients with CHARGE syndrome
• Hearing and swallowing in CHARGE syndrome
• Cochlear implants in CHARGE syndrome
• Neuroradiology findings in CHARGE syndrome and their relation with the clinical phenotype
• Exome sequencing in CHARGE patients without a CHD7 mutation
• Guidelines for CHD7 diagnostics
• Missense mutations in CHD7; interpretation and clinical phenotype

Our current research

• Database for CHD7 mutations
• Growth charts for children with CHARGE syndrome
• Puberty induction in CHARGE syndrome
• Early motor development in CHARGE syndrome

Contact person: Dr. M. Hitzert, MD, PhD clinical geneticist and coordinator of the centre of expertise Uniek email