CHARGE syndrome

CHARGE syndrome was formerly referred to as CHARGE association, which indicates a non-random pattern of congenital anomalies that occurs together more frequently than one would expect on the basis of chance, but for which a common cause has not been identified. Very few people with CHARGE will have 100% of its known features. In 2004, mutations on the CHD7 gene (located on Chromosome 8) were found in 10 of 17 patients in the Netherlands, making CHARGE an official syndrome.{{cite journal | vauthors = Vissers LE, van Ravenswaaij CM, Admiraal R, Hurst JA, de Vries BB, Janssen IM, van der Vliet WA, Huys EH, de Jong PJ, Hamel BC, Schoenmakers EF, Brunner HG, Veltman JA, van Kessel AG | title = Mutations in a new member of the chromodomain gene family cause CHARGE syndrome | journal = Nature Genetics | volume = 36 | issue = 9 | pages = 955–957 | date = September 2004 | pmid = 15300250 | doi = 10.1038/ng1407 | doi-access = free }} A 2006 US study of 110 individuals with CHARGE syndrome showed that 60% of those tested had a mutation of the CHD7 gene.{{cite journal | vauthors = Lalani SR, Safiullah AM, Fernbach SD, Harutyunyan KG, Thaller C, Peterson LE, McPherson JD, Gibbs RA, White LD, Hefner M, Davenport SL, Graham JM, Bacino CA, Glass NL, Towbin JA, Craigen WJ, Neish SR, Lin AE, Belmont JW | title = Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation | journal = American Journal of Human Genetics | volume = 78 | issue = 2 | pages = 303–314 | date = February 2006 | pmid = 16400610 | pmc = 1380237 | doi = 10.1086/500273 }}

In 2010, a review of 379 clinically diagnosed cases of CHARGE syndrome, in which CHD7 mutation testing was undertaken found that 67% of cases were due to a CHD7 mutation.{{cite journal | vauthors = Zentner GE, Layman WS, Martin DM, Scacheri PC | title = Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome | journal = American Journal of Medical Genetics. Part A | volume = 152A | issue = 3 | pages = 674–686 | date = March 2010 | pmid = 20186815 | pmc = 2918278 | doi = 10.1002/ajmg.a.33323 }}

The diagnosis of CHARGE syndrome is often difficult, because it is rare. The syndrome spans many disciplines, and as such, the symptoms may be recognized by a pediatrician, family medicine physician, oral and maxillofacial surgeon, ENT specialist, ophthalmologist, endocrinologist, cardiologist, urologist, developmental specialist, radiologist, geneticist, physiotherapist, occupational therapist, speech therapist, or orthopedic specialist.{{Cite web|date=2016-06-20|title=Genetics: Diagnosis, Testing & Recurrence {{!}} Charge Syndrome Foundation |url=https://www.chargesyndrome.org/ |access-date=2022-02-20 |website=Charge Syndrome Foundation {{!}} A better world for people with CHARGE Syndrome.|language=en}}

Although genetic testing positively identifies nearly two thirds of children with CHARGE syndrome, diagnosis is still largely clinical. The following signs were originally identified in children with this syndrome, but are no longer used to make the diagnosis alone.

• C – Coloboma of the eye, central nervous system anomalies
• H – Heart defects
• A – Atresia of the choanae
• R – Restricted growth and/or development
• G – Genital and/or urinary defects (hypogonadism, undescended testicles, besides hypospadias)
• E – Ear anomalies and/or deafness and abnormally bowl-shaped and concave ears, known as "lop ears".

Genetic testing for CHARGE syndrome involves specific genetic testing for the CHD7 gene. The test is available{{when|date=July 2016}} at most major genetic testing laboratories. Insurance companies sometimes do not pay for such genetic tests, though this is changing rapidly as genetic testing is becoming standard across all aspects of medicine. CHARGE syndrome is a clinical diagnosis, which means genetic testing is not required in order to make the diagnosis. Rather, the diagnosis can be made based on clinical features alone.

Once the diagnosis is made based on clinical signs, it is important to investigate other body systems that may be involved. For example, if the diagnosis is made based on the abnormal appearance of the ears and developmental delay, it is important to check the child's hearing, vision, heart, nose, and urogenital system. Ideally, every child newly diagnosed with CHARGE syndrome should have a complete evaluation by an ENT specialist, audiologist, ophthalmologist, pediatric cardiologist, developmental therapist, and pediatric urologist.

[https://onlinelibrary.wiley.com/doi/10.1002/ccr3.8670 Recent research] led by Yu Liang from Shijiazhuang Fourth Hospital and Sijie He from BGI Genomics, highlighted the use of prenatal ultrasound to detect CHARGE syndrome. Key findings indicated the difficulty in diagnosing CHARGE syndrome without genetic testing,{{cite journal | vauthors = Liang Y, He S, Yang L, Li T, Zhao L, Sun CX | title = CHARGE syndrome with early fetal ear abnormalities: A case report | journal = Clinical Case Reports | volume = 12 | issue = 3 | pages = e8670 | date = March 2024 | pmid = 38505478 | pmc = 10948373 | doi = 10.1002/ccr3.8670 }} {{lay source |template=cite news |url=https://www.bgi.com/global/news/study-reveals-how-fetal-ear-shape-could-signal-rare-genetic-condition-bgi-insight |title=Study Reveals How Fetal Ear Shape Could Signal Rare Genetic Condition |date= 2 May 2024 |work=BGI Insight |location= Shenzhen, China }} as mutations in the CHD7 gene are not always listed in public databases.{{cite web | title = Genome Aggregation Database | url = http://gnomad.broadinstitute.org/ }} and predicted to be deleterious by CADD{{cite web | url = https://cadd.gs.washington.edu/ | title = CADD }} and MutationTaster.{{cite web | url = https://www.mutationtaster.org/ | title = MutationTaster }}

Phenotypic variability further complicates diagnosis, with no clear correlation between mutation severity and clinical presentation. Trio-WES analysis confirmed a de novo mutation in the newborn, emphasizing the importance of early diagnosis for effective management. The study underscores the significance of early prenatal diagnosis through ultrasound examinations and specialized genetic testing. This approach facilitates timely interventions and enhances understanding of rare genetic conditions, improving diagnostic protocols for CHARGE syndrome and similar disorders.

Children with CHARGE syndrome may have a number of life-threatening medical conditions; with advances in medical care, these children can survive and can thrive with the support of a multidisciplinary team of medical professionals. Therapies and education must take into consideration hearing impairment, vision problems, and any others. Early intervention, such as occupational, speech-language, and physical therapy, to improve static posture, ambulation, and self-care skills is important. The intelligence of children with multiple health impairments, such as combined deafblindness, can be underestimated in the absence of early intervention.{{Cite web|date=2016-05-31|title=Therapies {{!}} Charge Syndrome Foundation|url=https://www.chargesyndrome.org/|access-date=2022-02-20|website=Charge Syndrome Foundation {{!}} A better world for people with CHARGE Syndrome.|language=en}}

Children with CHARGE syndrome will vary greatly in their abilities in the classroom: some may need little support, while some may require full-time support and individualized programs.

Taking each of the various affected body systems into account is vital to the success of the child in the educational setting.

An important step in dealing with abnormal behavior is understanding why it is occurring and helping the child learn more appropriate methods of communicating.{{Cite web|title=Education {{!}} Charge Syndrome Foundation|url=https://www.chargesyndrome.org/|access-date=2022-02-20|website=Charge Syndrome Foundation {{!}} A better world for people with CHARGE Syndrome.|language=en}}

The incidence is estimated to range from 0.1 to 1.2 per 10,000 live births, though the true incidence is unknown.{{cite journal | vauthors = Blake KD, Prasad C | title = CHARGE syndrome | journal = Orphanet Journal of Rare Diseases | volume = 1 | pages = 34 | date = September 2006 | pmid = 16959034 | pmc = 1586184 | doi = 10.1186/1750-1172-1-34 | doi-access = free }} As of 2005, the highest prevalence was found in Canada and estimated at 1 in 8,500 live births.{{cite journal | vauthors = Issekutz KA, Graham JM, Prasad C, Smith IM, Blake KD | title = An epidemiological analysis of CHARGE syndrome: preliminary results from a Canadian study | journal = American Journal of Medical Genetics. Part A | volume = 133A | issue = 3 | pages = 309–317 | date = March 2005 | pmid = 15637722 | doi = 10.1002/ajmg.a.30560 | s2cid = 23647735 | doi-access = free }}

B.D. Hall first described the CHARGE association in a 1979 journal paper of about 17 children who had been born with choanal atresia.{{cite journal | vauthors = Hall BD | title = Choanal atresia and associated multiple anomalies | journal = The Journal of Pediatrics | volume = 95 | issue = 3 | pages = 395–398 | date = September 1979 | pmid = 469662 | doi = 10.1016/S0022-3476(79)80513-2 }} During the same year, H.M. Hittner described 10 children who had choanal atresia as well as coloboma, congenital heart defect, and hearing loss.{{cite journal | vauthors = Hittner HM, Hirsch NJ, Kreh GM, Rudolph AJ | title = Colobomatous microphthalmia, heart disease, hearing loss, and mental retardation--a syndrome | journal = Journal of Pediatric Ophthalmology and Strabismus | volume = 16 | issue = 2 | pages = 122–128 | year = 1979 | pmid = 458518 | doi = 10.3928/0191-3913-19790301-10 }} Using both coloboma or choanal atresia and some of the other related characteristic malformations, R. A. Pagon first coined the acronym CHARGE in 1981 to emphasize that this cluster of associated malformations occurred together.

It came to be recognised{{when|date=July 2016}} as a syndrome within the umbrella of the CHARGE association, a set of apparently random signs occurring together. Since the signs seen in CHARGE are caused by a genetic anomaly, its name was eventually{{when|date=July 2016}} changed to 'CHARGE syndrome'.{{citation needed|date=July 2016}}

The CHARGE Syndrome Foundation, formally incorporated in 1993,{{Cite web|title=Foundation History {{!}} Charge Syndrome Foundation|url=https://www.chargesyndrome.org/|access-date=2021-12-09|website=Charge Syndrome Foundation {{!}} A better world for people with CHARGE Syndrome.|language=en}} is a US-based organization for individuals with CHARGE syndrome, families, researchers, and clinicians to further research and scientific knowledge about CHARGE Syndrome. The Foundation holds a biennial international conference that was first held in 1993.{{Cite web|title=Conferences {{!}} Charge Syndrome Foundation|url=https://www.chargesyndrome.org/|access-date=2021-12-09|website=Charge Syndrome Foundation {{!}} A better world for people with CHARGE Syndrome.|language=en}}

• List of syndromes
• Characteristics of syndromic ASD conditions

{{Reflist}}

• [https://www.chargesyndrome.org/ The CHARGE Syndrome Foundation]

{{Medical resources

| DiseasesDB = 32233

| ICD10 = {{ICD10|Q|87|8}}

| ICD9 = {{ICD9|759.89}}

| ICDO =

| OMIM = 214800

| MedlinePlus =

| eMedicineSubj = ped

| eMedicineTopic = 367

}}

{{Autism spectrum}}

{{Disorders of transcription and post transcriptional modification}}

{{Multiple abnormalities |state=autocollapse}}

Category:Genetic syndromes

Category:Syndromes affecting the eye

Category:Syndromes affecting the heart

Category:Syndromes affecting hearing

Category:Syndromic autism