CHARGE syndrome

CHARGE syndrome

Ear form characteristic of a person with CHARGE syndrome, along with her cochlear implant.
Classification and external resources
Specialty medical genetics
ICD-10 Q87.8
ICD-9-CM 759.89
OMIM 214800
DiseasesDB 32233
eMedicine ped/367

CHARGE syndrome (formerly known as CHARGE association), is a syndrome caused by a genetic disorder. It was first described in 1979.

In 1981, the term "CHARGE" came into use as an acronym for the set of unusual congenital features seen in a number of newborn children.[1] The letters stand for: coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital and/or urinary abnormalities, and ear abnormalities and deafness. These features are no longer used in making a diagnosis of CHARGE syndrome, but the name remains. CHARGE syndrome is the leading cause of congenital deafblindness.[2]

History

Dr. B.D. Hall first described the CHARGE association in a 1979 journal paper about 17 children who had all been born with choanal atresia.[3] About the same time, Dr. H.M. Hittner also observed that the group of 10 children in a study all had choanal atresia as well as coloboma, congenital heart defect, and hearing loss.[4] Using both a coloboma or choanal atresia and some of the other related characteristic malformations, Dr. R. A. Pagon first coined the term CHARGE.[1] In choosing this acronym, Dr. Pagon intended to emphasize that this cluster of associated malformations occurred together. It soon came to be recognised as a syndrome within the umbrella of the CHARGE association. While an association is a set of apparently random signs occurring together, the signs seen in CHARGE are caused by a genetic anomaly and so its name was officially corrected to 'CHARGE syndrome'.

Genetics

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. 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 a study conducted in the Netherlands, making CHARGE an official syndrome.[5] A further study in the US of 110 individuals with CHARGE syndrome showed that 60% of those tested had a mutation of the CHD7 gene.[6]

CHD7 is a member of the chromodomain helicase DNA-binding (CHD) protein family that plays a role in transcription regulation by chromatin remodeling.[7]

Most recently, a review of 379 published cases of clinically diagnosed cases of CHARGE syndrome in which CHD7 mutation testing was undertaken found that 67% of cases were due to a CHD7 mutation.[8]

Diagnosis

The diagnosis of CHARGE syndrome is often difficult, due to its rarity. This syndrome spans many disciplines, and as such, can be diagnosed by a pediatrician, oral and maxillofacial surgeon, ENT specialist, ophthalmologist, audiologist, endocrinologist, cardiologist, urologist, developmental specialist, radiologist, geneticist, physiotherapist, occupational therapist, speech therapist, or orthopedic specialist.

Signs

Although genetic testing positively identifies nearly two thirds of children with CHARGE syndrome, diagnosis is still largely clinical.. The acronym CHARGE was coined in 1981 to describe a cluster of features identified in a number of children. The following are the signs that were originally identified in children with this syndrome, but these features alone are no longer used in official diagnosis.

The most common genital condition associated with CHARGE syndrome in boys is undescended testicles, or cryptorchidism. Another commonly associated genital condition in boys is hypospadias.

Deafness is commonly seen in CHARGE syndrome. Aside from deafness, the most common ear anomaly seen in CHARGE syndrome is the abnormal appearance of bowl-shaped and concave ears, known as "lop ears".

Genetic testing

Genetic testing for CHARGE syndrome involves specific genetic testing for the CHD7 gene. As mentioned above, in a US study of 110 people, only 60% of those diagnosed clinically with CHARGE syndrome had a positive genetic test.

The availability of this genetic test is not widespread. The test is available at Emory University and the University of Chicago. The test is expensive, currently $2400 at the University of Chicago (plus additional costs charged by the facility or doctor's office that is actually drawing the blood). 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. For some physicians, the current standard of care is to diagnose cases of CHARGE syndrome based on clinical features alone.

Completion of diagnosis

Once the diagnosis of CHARGE syndrome is made based on some of the clinical signs, it is important to investigate the other body systems that may be involved.

For example, if the diagnosis of CHARGE syndrome 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 urological system (check for hypospadias, undescended testicles, or other urinary abnormalities). Thus, every child newly diagnosed with CHARGE syndrome should have a complete evaluation by an ENT specialist, audiologist (to check for hearing, unless this is also checked by the ENT specialist), ophthalmologist, pediatric cardiologist, developmental therapist, and pediatric urologist.

Epidemiology

The true incidence of CHARGE syndrome is not known though it is estimated to range from 0.1–1.2 per 10,000 live births.[9] The highest prevalence of CHARGE syndrome was found in Canada and estimated at 1 in 8,500 live births.[10]

Therapy and outcome

Children with CHARGE syndrome can have many life-threatening issues; with advances in medical care these children can survive and become healthy and happy individuals. Appropriate therapies and educational intervention for individuals with CHARGE syndrome must take into consideration hearing impairment, vision problems, and any other medical conditions that are present. Early intervention, such as occupational, speech-language, and physical therapy, is very important as the intelligence of children with multiple health issues such as combined deaf-blindness is often underestimated. Because of the developmental delay, early intervention can play an important role in promoting mobility, improving static postures, transitioning towards ambulation, and teaching self-care skills. Both physicians and parents need to be made aware that these children can thrive with the support of a team of medical professionals. Management should be by a multidisciplinary team and coordinated by a single person, if possible.

Education

Parents of children with CHARGE syndrome should be encouraged to be "in charge" and active advocates for their children in order to ensure development of an educational program that will allow each child to reach his or her full potential. 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.

In an educational setting, all involved must be aware of the various systems in the body that can be affected with CHARGE syndrome. Taking each of these into account is vital to the success of the child in the educational setting.

A professional packet for educators and other professionals working with children who have CHARGE syndrome is available for downloading at CHARGE Syndrome Professional Packet. This packet covers a wide variety of issues educators and therapists in various settings may face if they are working with a student who has CHARGE syndrome.

Understanding behaviors

Parents, teachers and caregivers should understand that all behaviors, whether good or bad, are a form of communication. An important step in dealing with the behavior is understanding why it is occurring in the first place and helping the child learn more appropriate methods of communicating.

Transitioning into adulthood

Parents should make sure that before their child reaches age 18 (or the age of maturity in their country), they have established which doctors and specialists will follow the individual with CHARGE syndrome in adulthood. Even if the young adult with CHARGE is independent, it’s important to help them maintain their independence by helping them move from the pediatric doctors to the new doctors who will follow them as adults.

References

  1. 1 2 Pagon RA, Graham JM, Zonana J, Yong SL (1981). "Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association". J. Pediatr. 99 (2): 223–7. doi:10.1016/S0022-3476(81)80454-4. PMID 6166737.
  2. ↑ National Deaf-Blind Child Count Summary
  3. ↑ Hall BD (1979). "Choanal atresia and associated multiple anomalies". J. Pediatr. 95 (3): 395–8. doi:10.1016/S0022-3476(79)80513-2. PMID 469662.
  4. ↑ Hittner HM, Hirsch NJ, Kreh GM, Rudolph AJ (1979). "Colobomatous microphthalmia, heart disease, hearing loss, and mental retardation--a syndrome". Journal of pediatric ophthalmology and strabismus 16 (2): 122–8. PMID 458518.
  5. ↑ Vissers, L. E., van Ravenswaaij, C. M., Admiraal, R., Hurst, J. A., de Vries, B. B., Janssen, I. M.; et al. (2004). "Mutations in a new member of the chromodomain gene family cause CHARGE syndrome.". Nature Genetics 36 (9): 955–957. doi:10.1038/ng1407. PMID 15300250.
  6. ↑ Lalani SR, Safiullah AM, Fernbach SD; et al. (2006). "Spectrum of CHD7 Mutations in 110 Individuals with CHARGE Syndrome and Genotype-Phenotype Correlation". Am. J. Hum. Genet. 78 (2): 303–14. doi:10.1086/500273. PMC 1380237. PMID 16400610.
  7. ↑ Janssen, N; Bergman, JE; Swertz, MA; Tranebjaerg, L; Lodahl, M; Schoots, J; Hofstra, RM; van Ravenswaaij-Arts, CM; Hoefsloot, LH (August 2012). "Mutation update on the CHD7 gene involved in CHARGE syndrome.". Human Mutation 33 (8): 1149–1160. doi:10.1002/humu.22086. PMID 22461308.
  8. ↑ Zentner GE, Layman WS, Martin DM, Scacheri PC (2010). "Molecular and phenotypic aspects of CHD7 mutation in CHARGE syndrome". Am J Med Genet A 152 (3): 674–686. doi:10.1002/ajmg.a.33323. PMC 2918278. PMID 20186815.
  9. ↑ Blake, KD; Prasad, C (Sep 7, 2006). "CHARGE syndrome.". Orphanet journal of rare diseases 1: 34. doi:10.1186/1750-1172-1-34. PMC 1586184. PMID 16959034.
  10. ↑ Issekutz, KA; Graham JM, Jr; Prasad, C; Smith, IM; Blake, KD (Mar 15, 2005). "An epidemiological analysis of CHARGE syndrome: preliminary results from a Canadian study.". American journal of medical genetics. Part A 133A (3): 309–17. doi:10.1002/ajmg.a.30560. PMID 15637722.

External links

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