CHARGE syndrome

CHARGE syndrome is an acronym that classically describes a combination head and neck, cardiac, CNS and genitourinary disorders:

• C: coloboma
• H: heart defects (congenital heart disease)
• A: atresia (choanal)
• R: retardation (mental)
• G: genital hypoplasia
• E: ear abnormalities/deafness

PathologyClinical presentation

ItCHARGE syndrome is thought to occur due to disturbance in embryonic differentiation ~35^th to 45^th day of gestation.

Genetics

Most casesusually suspected at birth once multiple congenital abnormalities are sporadic but there are occasional autosomal dominant formsidentified. Approximately two-thirds of cases is caused by a defect in the CHD7 gene on chromosome 8 ⁴.

Diagnosis

The diagnosis of CHARGE syndrome can be made on clinical grounds ⁶:

• definite CHARGE syndrome: four major characteristics or three major characteristics and three minor characteristics
• possible/probable CHARGE syndrome: one-to-two major characteristics and several minor characteristics

Major criteria

• coloboma (~85%)
• choanal atresia/stenosis (~55%) (or cleft palate)
• cranial nerve dysfunction, e.g. facial palsy (~40%), dysphagia (~80%)
• CHARGE syndrome ear (some or all of the following)
  • atretic outer ear
  • ossicular chain malformation
  • Mondini malformation
  • absent/hypoplastic semicircular canals

Minor criteria

• genital hypoplasiaurogenital abnormalities
  • kidney
    • duplex kidney
    • developmental delayrenal hypoplasia/solitary kidney
  • penis
    • hypospadias
    • penile agenesis
  • scrotum/testicles
    • bifid scrotum
    • cryptorchidism
  • vaginal atresia
  • uterine atresia
• congenital heart disease, e.g.
  • tetralogy of Fallot
  • atrioventricular canal defect
  • double outlet right ventricle
• short stature
• cleft palate +/- lip
• oesophageal atresia / tracheo-oesophageal fistula (~15%) ²
• characteristic facies
• developmental delay

Associations

• microphthalmia/anophthamiaanophthalmia
• intra-uterine growth retardation (IUGR)
• congenital renal anomalies
• coronal clival cleft ⁷

Treatment and prognosis

The prognosis is variable dependentdepending on the extent of defects. In sporadic forms, the risk of recurrence is at ~1%.

History and etymology

This constellation of pathology was initially described by B D Hall and separately by H M Hittner in 1979. The term "CHARGE" was first coined by R A Pagon to describe an association between the symptoms and subsequent work isolated a common genetic defect seen in 60% of individuals: the CHD7 defect.