CHARGE syndrome

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

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 :

  • 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
Associations

Pathology

CHARGE syndrome is thought to occur due to a disturbance in embryonic differentiation ~35 to 45 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 .

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 independently 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.