CHARGE Syndrome

Original Editor - Angeliki Chorti Top Contributors - Angeliki Chorti

Introduction[edit | edit source]


CHARGE syndrome is an autosomal dominant genetic syndrome that presents with a nonrandom pattern of congenital anomalies attributed to mutations in the CHD7 gene.[1] The CHD7 (chromodomain helicase DNA binding protein) gene, present on 8q12 and involved in the aetiology of this syndrome, is responsible for several structural and physiological processes leading to abnormalities. [2] Differences in clinical presentation are the result of unique mutations scattered throughout the gene in the majority of cases. [2]

CHARGE syndrome was initially called Hall-Hittner syndrome since Hall and Hittner were the first to identify it. [3] Later, the name changed to "CHARGE" due to the cluster of features often seen in these cases. The letters stand for: Coloboma of the eye, Heart defects, Atresia of the choanae, Restriction of growth and develpment, and Ear abnormalities and deafness.

Its estimated prevalence is over 1:10,000 and growing, so greater awareness of this condition is deemed necessary to improve survival and outcome. [4][5]

Clinical features[edit | edit source]

Cardinal anomalies related to CHARGE syndrome were first described by Pagon: [3]

  • eye coloboma
  • choanal atresia
  • heart defects
  • genital hypoplasia
  • retarded growth and development
  • behavioural problems and autistic-like behaviour
  • ear malformation and deafness.

A consistent reported feature in CHARGE syndrome is semicircular canal hypoplasia resulting in vestibular areflexia. [2]

Other commonly associated congenital anomalies are: [2]

Diagnosis[edit | edit source]

Diagnosis of CHARGE syndrome is usually determined during the prenatal or neonatal period, initially through the identification of dysmorphic and congenital anomalies. [3]

Diagnostic criteria were initially developed by Blake et al.[4] and further modified by Verloes, [6] who highlighted the importance of the 3C triad (coloboma, choanal atresia, abnormal semicircular canals). Other criteria include orofacial cleft, distinctive facial appearance, tracheoesophageal fistula, limb abnormalities, and rarely, immune deficiencies. [3]

Diagnostic criteria Major Minor Occasional
Blake et al. [4]

Diagnostic criteria interpretation: Definite CHARGE: 4 major or 3 major and 3 minor criteria

Probable/possible CHARGE: 1 or 2 major and several minor criteria


Coloboma -of iris, retina, choroid, disc; microphthalmia;

Choanal atresia;

Cranial nerve (especially VII and VIII) dysfunction;

Characteristic ear abnormalities

Genital hypoplasia;

Developmental delay;

Cardiovascular malformations;

Growth deficiency;

Orofacial cleft;

Tracheoesophageal fistula;

Characteristic face

Renal anomalies;

Hand anomalies;

Abdominal defects;

Spine anomalies;

Neck/shoulder anomalies;

Thymic/parathyroid hypoplasia

Verloes [6]

Diagnostic criteria interpretation:

Typical CHARGE: 3 major, or 2 major and 2 minor criteria

Partial/incomplete CHARGE: 2 major and 1 minor criteria

Atypical CHARGE: 2 major, or 1 major and 3 minor criteria


Coloboma (iris or choroid, with or without microphthalmia);

Choanal atresia;

Hypoplastic semi-circular Canals

Rhombencephalic dysfunction (brainstem dysfunctions, cranial nerve VII to XII palsies and neurosensory deafness);

Hypothalamo-hypophyseal dysfunction (including GH and gonadotrophin deficiencies;

Abnormal middle or external ear;

Malformation of mediastinal organs (heart, esophagus);

Mental retardation

Genetic testing is then carried out to establish a definite diagnosis and confirm the initial suspicion for this genetic disorder. [5]

Differential Diagnosis[edit | edit source]

Differential diagnosis may involve the following syndromes: [5]

  • Abruzzo-Erickson syndrome,
  • Kallmann syndrome,
  • 22q11.2 deletion syndrome,
  • VACTERL/VATER association,
  • Kabuki syndrome,
  • Renal coloboma syndrome,
  • Cat-eye syndrome,
  • Joubert syndrome,
  • BOR syndrome,
  • 5q11.2 microdeletion syndrome and other chromosomal microdeletion syndromes.

Management[edit | edit source]

Management of CHARGE syndrome is complex and lifelong.[7] Due to the broad phenotype that can be expressed, almost all organ and sensory systems can be affected, resulting in a high and extremely variable comorbidity and severity. [8]

Trider et al. [9] have produced a health supervision checklist for examination and treatment across the lifespan, you can find this here. Involved areas for inspection and management are:

  • Genetics
  • Neurology
  • Eyes, ears, nose and throat
  • Cardiology / Respiratory
  • Gastroenterology / Genitourinary
  • Endocrinology
  • Immune system
  • Musculoskeletal
  • Psychology / Developmental

A Multidisciplinary Approach to Management[edit | edit source]

The nature and broad expression of CHARGE syndrome cases leads to a multi-disciplinary approach to management.

This may involve a range of services across the lifespan such as:

  • genetic counseling,
  • neurologists,
  • cardiologists,
  • dieticians,
  • gastroenterologists,
  • endocrinologists,
  • surgical management, e.g. for cochlear implant, heart abnormalities, repair of cleft lip / palate
  • services for persons with vision and hearing loss,
  • physiotherapy,
  • occupational therapy,
  • speech/language therapy,
  • psychiatric interventions
  • behavior therapy and psychological counseling.

Resources[edit | edit source]

The CHARGE Syndrome Foundation

Guidelines: Neuroradiological evaluation

References[edit | edit source]

  1. Hsu P, Ma A, Wilson M, Williams G, Curotta J, Munns CF, Mehr S. CHARGE syndrome: a review. J Paediatr Child Health. 2014 Jul;50(7):504-11.
  2. 2.0 2.1 2.2 2.3 Jongmans MC, Admiraal RJ, van der Donk KP, Vissers LE, Baas AF, Kapusta L, van Hagen JM, Donnai D, de Ravel TJ, Veltman JA, Geurts van Kessel A, De Vries BB, Brunner HG, Hoefsloot LH, van Ravenswaaij CM. CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. 2006 Apr;43(4):306-14.
  3. 3.0 3.1 3.2 3.3 Usman N, Sur M. CHARGE Syndrome. 2023 Mar 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan.
  4. 4.0 4.1 4.2 Blake KD, Davenport SL, Hall BD, Hefner MA, Pagon RA, Williams MS, Lin AE, Graham JM Jr. CHARGE association: an update and review for the primary pediatrician. Clin Pediatr (Phila) 1998 Mar; 37(3):159-73.
  5. 5.0 5.1 5.2 Orphanet. CHARGE Syndrome. Available from: [accessed 7/5/2023]
  6. 6.0 6.1 Verloes A. Updated diagnostic criteria for CHARGE syndrome: a proposal. Am J Med Genet A. 2005 Mar 15;133A(3):306-8.
  7. Allen T. CHARGE syndrome: diagnosis and clinical management in the NICU. Adv Neonatal Care. 2012 Dec;12(6):336-42; quiz 343-4.
  8. de Geus CM, Free RH, Verbist BM, Sival DA, Blake KD, Meiners LC, van Ravenswaaij‐Arts CM.Guidelines in CHARGE syndrome and the missing link: Cranial imaging. Am J Med Genet C Semin Med Genet. 2017 Dec; 175(4): 450–464.
  9. Trider C‐L, Arra‐Robar A, van Ravenswaaij‐Arts C, Blake K. Developing a CHARGE syndrome checklist: Health supervision across the lifespan (from head to toe). Am J Med Genet A, 2017; 173A: 684–91.