CHARGE syndrome

Last revised by Joshua Yap on 26 Mar 2023

CHARGE syndrome is a phenotype associated with CHD7 gene mutation originally defined by a constellation of congenital anomalies:

According to updated diagnostic criteria, the most defining features are the 4 Cs:

  • coloboma
  • choanal atresia
  • cranial nerve anomalies (especially olfactory pathway absence)
  • characteristic ear anomalies (especially semicircular canal dysplasia/aplasia)

The incidence is 1-12 per 100,000 births 6.

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

The diagnosis of CHARGE syndrome can be made on clinical grounds 6,11:

  • definite CHARGE syndrome: 4 major characteristics or 3 major plus 3 minor characteristics
  • possible/probable CHARGE syndrome: one or two major characteristics and several minor characteristics
  1. coloboma (80%): ranges from defect of iris, retina, choroid, or disc, to microphthalmia or anophthalmia
  2. choanal atresia/stenosis (45%) or cleft palate (25-50%)
  3. cranial nerve anomaly/dysfunction
    • olfactory (90%): hyposmia/anosmia
    • facial (40%): facial palsy
    • vestibulocochlear (95-100%): sensorineural deafness
    • glossopharyngeal or vagal (60-80%): velopharyngeal incoordination for suck/swallow
  4. characteristic ear anomalies (some or all of the following) (90%)
    • abnormal auricle: short and wide (lop/cup shaped), absent lobule, truncated helix, prominent antihelix
    • ossicular malformations
    • Mondini malformation
    • absent/hypoplastic semicircular canals

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

Most cases are sporadic but there are occasional autosomal dominant forms. Approximately two-thirds of cases are caused by a defect in the CHD7 (chromodomain helicase DNA-binding protein 7) gene on chromosome 8 4,7.

All CHARGE patients are indicated to undergo CT of the temporal bone and MRI of the brain, ideally in the same anesthesia session 11.

Temporal bone CT demonstrates the following abnormalities: 

Brain MRI demonstrates the following abnormalities 7,9:

  • temporal bone
    • vestibular dysplasia (100%)
    • semicircular canal dysplasia (100%)
    • internal auditory canal dysplasia (100%)
    • cochlear dysplasia (89%)
    • cochlear nerve deficiency/absence (15-83%) 8
    • absent cochlear aperture (44%)
    • enlarged vestibular aqueduct (6%)
  • face
    • cleft lip/palate (50%)
    • parotid dysplasia (60%)
    • coloboma (40%)
    • choanal atresia (20%)
  • skull base
    • basioccipital hypoplasia (90%)
    • coronal clival cleft (87%)
    • dorsally angulated clivus (70%)
    • J-shaped sella (70%)
    • bony olfactory groove dysplasia (75%)
  • brain
    • olfactory nerve hypoplasia (100%)
    • olfactory sulcus dysplasia (100%)
    • brainstem hypoplasia (50%)
    • ventriculomegaly (30%)
    • vermian hypoplasia (20%)

The prognosis is variable depending on the extent of defects.

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.

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Cases and figures

  • Case 1: pneumonia and CHARGE syndrome
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