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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
For the benefit of patients.

IllnessCHARGE syndrome, differential diagnosis

Summary

Short information

A guideline-curated gene sequence analysis plus 22 additional gene analyses according to the clinical suspicion CHARGE syndrome

ID
CP0250
Number of genes
22 Accredited laboratory test
Examined sequence length
9,0 kb (Core-/Core-canditate-Genes)
72,4 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

[Sanger]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
CHD78994NM_017780.4AD
BMP41227NM_001202.6AD, AR
EFTUD22919NM_004247.4AD
EYA11779NM_000503.6AD
FGFR12469NM_023110.3AD
GLI24761NM_005270.5AD
GLI34743NM_000168.6AD
JAG13657NM_000214.3AD
KDM6A4206NM_021140.4XL
KMT2D16614NM_003482.4AD
MYCN1395NM_005378.6AD
OTX2870NM_172337.3AD
PAX21254NM_003987.5AD
POLR1C1041NM_203290.4AR
POLR1D402NM_015972.4AD, AR
SEMA3E2328NM_012431.3AR
SIX1855NM_005982.4AD
SIX52220NM_175875.5AD
SOX2954NM_003106.4AD
TBX221563NM_001109878.2XL
TCOF14467NM_001135243.2AD
ZEB23645NM_014795.4AD

Informations about the disease

Clinical Comment

Full-blown CHARGE syndrome includes coloboma, heart defects, atresia choanae, delayed growth, genital and ear abnormalities. The pattern of malformations varies among affected individuals, and the multiple health problems can be life-threatening in infancy. Most CHARGE patients present with colobomas, sometimes along with microphthalmia. Often one or both choanae are blocked, and cranial nerve function is impaired with dysphagia, facial paralysis, hyposmia/anosmia, mild to profound hearing loss also due to middle and inner ear abnormalities. The auricles may be abnormally shaped. Other features include heart defects, slow growth in late infancy, delayed development of motor skills, cleft lip and/or palate, hypogonadotropic hypogonadism, and tracheoesophageal fistulas. Most individuals with CHARGE syndrome also have prominent facial features including facial asymmetry. Affected individuals show a wide range of cognitive functioning, from normal intelligence to severe learning disabilities with absent speech as well as impaired communication. Less common features include kidney abnormalities, immune system problems, scoliosis/kyphosis and limb deformities. Inheritance is autosomal dominant, with many patients harboring spontaneous mutations. When the diagnostic criteria are strictly applied, 90% of affected individuals show pathogenic CHD7 mutations, although from a clinical point of view CHARGE syndrome is often merely to be ruled out, so that the molecular genetic yield is then more like 35%: 98% DNA sequence variations are matched by only 2% duplications/deletions. Atypical phenotypes additionally complicate definitive statements on molecular genetic diagnostic yield.

References: https://www.ncbi.nlm.nih.gov/books/NBK1117/

 

Synonyms
  • DD syndromes: Kallmann s., Kabuki s., VACTERL, Renal coloboma s., Cat-eye s., Joubert s., BOR s.
  • Sympt.: Coloboma, Heart anomaly, choanal Atresia, Retardation, Genital + Ear anomalies, CHARGE
  • Alias: CHARGE association
  • Alias: Hall-Hittner syndrome
  • Allelic: Anterior segment anomalies with/-out cataract (EYA1)
  • Allelic: Deafness, AD 23 (SIX1)
  • Allelic: Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
  • Allelic: Glomerulosclerosis, focal segmental, 7 (PAX2)
  • Allelic: Hajdu-Cheney syndrome (NO`TCH2)
  • Allelic: Holoprosencephaly 9 (GLI2)
  • Allelic: Leukodystrophy, hypomyelinating, 11 (POLR1C)
  • Allelic: Microphthalmia, syndromic 5 (OTX2)
  • Allelic: Osteoglophonic dysplasia (FGFR1)
  • Allelic: Polydactyly, postaxial, types A1 + B (GLI3)
  • Allelic: Polydactyly, preaxial, type IV (GLI3)
  • Allelic:Trigonocephaly (FGFR1)
  • Abruzzo-Erickson [CHARGE-like, XL] syndrome (TBX22)
  • Alagille syndrome 1 (JAG1)
  • Alagille syndrome 2 (NOTCH2)
  • Branchiootic syndrome 1 (EYA1)
  • Branchiootic syndrome 3 (SIX1)
  • Branchiootorenal syndrome 1, with/-out cataracts (EYA1)
  • Branchiootorenal syndrome 2 (SIX5)
  • Cleft palate with ankyloglossia (TBX22)
  • Culler-Jones syndrome [Hypopituitarism, growth hormone deficiency, +/- postaxial polydactyly] (GLI2)
  • Deafness, congenital heart defects + posterior embryotoxon (JAG1)
  • Feingold syndr. 1 [microceph., limb malform., esophagus + duodenal atresia, learn disab./MR] (MYCN)
  • Greig cephalopolysyndactyly syndrome (GLI3)
  • Hartsfield syndrome [holoprosencephaly, ectrodactyly, cleft/lip palate] (FGFR1)
  • Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
  • Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
  • Jackson-Weiss syndrome (FGFR1)
  • Kabuki syndrome 1 (KMT2D)
  • Kabuki syndrome 2 (KDM6A)
  • Leukoencephalopathy with dystonia + motor neuropathy (SEMA3E)
  • Mandibulofacial dysostosis, Guion-Almeida type (EFTUD2)
  • Microphthalmia, syndromic 3 (SOX2)
  • Microphthalmia, syndromic 6 (BMP4)
  • Mowat-Wilson syndrome [complex developmental disorder] (ZEB2)
  • Optic nerve hypoplasia + abnormalities of the central nervous system (SOX2)
  • Orofacial cleft 11 (BMP4)
  • Otofaciocervical syndrome (EYA1)
  • Pallister-Hall s. [Hypothal. hamart., pituit. dysfunct, cent. polydactyly, visc. malform.] (GLI3)
  • Papillorenal syndrome (PAX2)
  • Pfeiffer syndrome (FGFR1)
  • Pituitary hormone deficiency, combined, 6 (OTX2)
  • Retinal dystrophy, early-onset, with/-out pituitary dysfunction (OTX2)
  • Tetralogy of Fallot (JAG1)
  • Treacher Collins syndrome 1 (TCOF1)
  • Treacher Collins syndrome 2 (POLR1D)
  • Treacher Collins syndrome 3 (POLR1C)
Heredity, heredity patterns etc.
  • AD
  • AR
  • XL
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined