CHARGE syndrome
Encyclopedia
CHARGE syndrome 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. 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.
. 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. Using both a coloboma or choanal atresia and some of the other related characteristic malformations, Dr. R. A. Pagon first coined the term CHARGE. 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'.
gene (located on Chromosome 8) were found in 10 of 17 patients in a study conducted in the Netherlands, making CHARGE an official "syndrome". A further study in the US of 110 individuals with CHARGE syndrome showed that 60% of those tested had a mutation on the CHD7 gene.
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 CHD7
mutation.
The most common genital condition associated with CHARGE syndrome is undescended testicles, or cryptorchidism
. Another commonly associated genital condition 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".
of the test is about 60%.
The availability of this genetic test is not widespread. Currently, the major lab testing facility, Quest Diagnostics, does not test for CHARGE syndrome. The test is available at Emory University
and the University of Chicago
. The test is very 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 normally do not pay for such genetic tests, especially if the current standard of care is to diagnose cases of CHARGE syndrome based on clinical features.
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.
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 download 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.
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
caused by a genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
. 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. The letters stand for: Coloboma
Coloboma
A coloboma is a hole in one of the structures of the eye, such as the iris, retina, choroid or optic disc...
of the eye, Heart defects, Atresia
Atresia
Atresia is a condition in which a body orifice or passage in the body is abnormally closed or absent.Examples of atresia include:* Imperforate anus - malformation of the opening between the rectum and anus....
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.
History of CHARGE
Dr. B.D. Hall first described the CHARGE association in a 1979 journal paper about 17 children who had all been born with choanal atresiaChoanal atresia
Choanal atresia is a congenital disorder where the back of the nasal passage is blocked, usually by abnormal bony or soft tissue formed during fetal development.-Presentation:It can be unilateral or bilateral....
. 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. Using both a coloboma or choanal atresia and some of the other related characteristic malformations, Dr. R. A. Pagon first coined the term CHARGE. 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 CHD7CHD7
Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene....
gene (located on Chromosome 8) were found in 10 of 17 patients in a study conducted in the Netherlands, making CHARGE an official "syndrome". A further study in the US of 110 individuals with CHARGE syndrome showed that 60% of those tested had a mutation on the CHD7 gene.
Most recently, a review of 379 published cases of clinically diagnosed cases of CHARGE syndrome in which CHD7
CHD7
Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene....
mutation testing was undertaken found that 67% of cases were due to CHD7
CHD7
Chromodomain-helicase-DNA-binding protein 7 also known as ATP-dependent helicase CHD7 is an enzyme that in humans is encoded by the CHD7 gene....
mutation.
Diagnosis
The diagnosis of CHARGE syndrome is often missed, due to the rarity of the condition. However, this syndrome spans many disciplines, and as such, can be diagnosed by the pediatrician, Oral and maxillofacial surgeon, ENT specialist, ophthalmologist, cardiologist, urologist, developmental specialist, radiologist, or geneticist.Signs
Although genetic testing positively identifies nearly two thirds of the total number of children with CHARGE, diagnosis is still largely clinical.http://www.chargesyndrome.org/about-charge.asp. 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.- C - ColobomaColobomaA coloboma is a hole in one of the structures of the eye, such as the iris, retina, choroid or optic disc...
of the eyeHuman eyeThe human eye is an organ which reacts to light for several purposes. As a conscious sense organ, the eye allows vision. Rod and cone cells in the retina allow conscious light perception and vision including color differentiation and the perception of depth...
, central nervous systemCentral nervous systemThe central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
anomalies - H - Heart defects
- A - Atresia of the choanaeChoanal atresiaChoanal atresia is a congenital disorder where the back of the nasal passage is blocked, usually by abnormal bony or soft tissue formed during fetal development.-Presentation:It can be unilateral or bilateral....
- R - Retardation of growth and/or development
- G - Genital and/or urinary defects (HypogonadismHypogonadismHypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
) - E - Ear anomalies and/or deafness
The most common genital condition associated with CHARGE syndrome is undescended testicles, or cryptorchidism
Cryptorchidism
Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
. Another commonly associated genital condition is hypospadias
Hypospadias
Hypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus...
.
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. Therefore, the known sensitivitySensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
of the test is about 60%.
The availability of this genetic test is not widespread. Currently, the major lab testing facility, Quest Diagnostics, does not test for CHARGE syndrome. The test is available at Emory University
Emory University
Emory University is a private research university in metropolitan Atlanta, located in the Druid Hills section of unincorporated DeKalb County, Georgia, United States. The university was founded as Emory College in 1836 in Oxford, Georgia by a small group of Methodists and was named in honor of...
and the University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...
. The test is very 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 normally do not pay for such genetic tests, especially if the current standard of care is to diagnose cases of CHARGE syndrome based on clinical features.
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.
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 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 very active advocates for their children in order to ensure development of an educational program that will allow each child to reach their full potential. Children with CHARGE syndrome will vary greatly in their abilities in the classroom: some may need very 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 download 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 majority 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.External links
- CHARGE Syndrome Foundation
- CHARGE Syndrome Book, published August 2010
- GeneReviews: CHARGE syndrome
- Personal Account of CHARGE Syndrome
- Canadian CHARGE Syndrome Group
- Texas CHARGE Syndrome Group
- Canadian Deafblind and Rubella Association
- CHARGE Syndrome Association of Australasia
- German CHARGE Syndrome Site
- UK CHARGE Support Group
- Swiss CHARGE Syndrome site
- Sense UK