CHARGE syndrome

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

• C: coloboma
• H: heart defects (congenital heart disease)
• A: atresia (choanal)
• R: retardation of growth and development
• G: genital and/or urinary abnormalities
• E: ear abnormalities and/or deafness

Clinical presentation

CHARGE syndrome is usually suspected at birth once multiple congenital abnormalities are identified. 

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

• urogenital abnormalities
  • kidney
    • duplex kidney
    • renal hypoplasia/solitary kidney
  • penis
    • hypospadias
    • penile agenesis
  • scrotum/testicles
    • bifid scrotum
    • cryptorchidism
  • vaginal atresia
  • uterine atresia
• congenital heart disease
  • 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/anophthalmia
• intra-uterine growth restriction (IUGR)
• congenital renal anomalies
• coronal clival cleft ⁷
• agenesis/hypoplasia of semicircular canals (highly characteristic) ^8,9

Pathology

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

Genetics

Most cases are sporadic but there are occasional autosomal dominant forms. Approximately two-thirds of cases are caused by a defect in the CHD7 gene on chromosome 8 ^4,7.

Treatment and prognosis

The prognosis is variable depending 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 separatelyindependently 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.