• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • Resources
  • References
  • Programs & Resources
  • Complete Report

CHARGE Syndrome


Last updated: September 05, 2018
Years published: 1988, 1988, 1990, 1996, 1997, 1998, 2000, 2002, 2007, 2008, 2012, 2015, 2018


NORD gratefully acknowledges John M. Graham, JR., M.D., Sc.D., Pediatric Consultant in Clinical Genetics and Dysmorphology, Department of Pediatrics, Cedars-Sinai Medical Center and Harbor-UCLA Medical Center for assistance in the preparation of this report.

Disease Overview

CHARGE syndrome is a rare disorder that arises during early fetal development and affects multiple organ systems. The CHARGE acronym comes from the first letter of some of the more common features seen in these children: (C) = coloboma (usually retinochoroidal) and cranial nerve defects (80-90%) (H) = heart defects in 75-85%, especially tetralogy of Fallot (A) = atresia of the choanae (blocked nasal breathing passages) (50-60%) (R) = retardation of growth (70-80%) and development (G) = genital underdevelopment due to hypogonadotropic hypogonadism (E) = ear abnormalities and sensorineural hearing loss (>90%). Diagnosis is based on a specific set of features (see below). In addition to the CHARGE features above, most children with CHARGE syndrome have other features, including characteristic facial features: asymmetric facial nerve palsy, cleft lip or palate, esophageal atresia (blind-ending food pipe) or tracheoesophageal fistula (connection between the wind pipe and the food pipe). The symptoms of CHARGE syndrome vary greatly from one child to another. The cause of CHARGE is usually a new mutation (change) in the CHD7 gene, or rarely, genomic alterations in the region of chromosome 8q12.2 where the CHD7 gene is located. Among 119 French children with CHARGE syndrome, CHD7 mutations were found in 83% of typical CHARGE syndrome individuals, and 58% of atypical cases. The following cardinal symptoms were found among CHD7+ cases: coloboma 73%; heart defects 63%; choanal atresia 43%; IUGR 24%; genital abnormalities 56%; semicircular canal agenesis/hypoplasia 99%; deafness 97%; external ear anomalies 86%; internal ear anomalies (SCC defects excluded) 65%; anosmia 83%; olfactory bulb agenesis 76%; cranial nerve defects 74%; intellectual disability 62%; CNS defects 51%; kidney 31%; esophageal anomalies 24%; and cleft lip and/or palate 20%. Postnatal growth failure and swallowing problems are very frequent associated with cranial nerve dysfunctions. Three-dimensional reconstructions of MRI scans showed temporal bone abnormalities in over 85%.

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  • CHARGE association
  • Hall-Hittner syndrome
  • coloboma, heart, atresia of the choanae, retardation of growth and development, genital and urinary anomalies, and ear anomalies
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Signs & Symptoms

CHARGE syndrome affects multiple organ systems, resulting in multiple problems apparent at birth. Other characteristics of CHARGE syndrome may not become apparent until later in life. The diagnosis of CHARGE syndrome should be made by a medical geneticist based on the presence of at least one major criterion and several minor and/or occasional criteria of CHARGE syndrome (see below).

Major Diagnostic Criteria (The 4 C’s):
Features seen commonly in CHARGE, rarely in other conditions: Coloboma, Cranial nerve abnormalities, Choanal atresia, typical CHARGE Ear.

A coloboma is a cleft or failure to close of the eyeball during fetal development. This can result in a keyhole-shaped pupil (iris coloboma) and/or abnormalities in the retina, macula or optic nerve. Very small eyes (microphthalmia) or missing eyes (anophthalmia) can be severe forms of coloboma. Colobomas of the retina or optic nerve may result in significant vision loss, including blind spots, problems with depth perception or legal blindness. Colobomas occur most frequently in the retina and are present in at least 70-90% of patients with CHARGE syndrome. Examination of 38 eyes in 19 patients with CHARGE syndrome and confirmed CHD7 mutations revealed colobomata affected the posterior segment of 35 eyes in 18 patients. Both retinochoroidal and optic disk colobomata were observed bilaterally in 15 patients and unilaterally in 3 patients. The coloboma involved the macula totally or partially in 21 eyes of 13 patients. Bilateral large retinochoroidal colobomata are the typical ophthalmic feature of CHARGE syndrome in patients with confirmed CHD7 mutations; however, even eyes with large colobomata can form maculas. Many children with colobomas (even just an iris coloboma) may be sensitive to bright light (photophobia). Surgery cannot correct ocular colobomas. Near-sightedness or far-sightedness can be helped with glasses. Sunglasses and a hat with a protective bill can help the photophobia.

Cranial nerve abnormalities
Sensorineural (nerve) hearing loss in CHARGE is due to abnormalities in cranial nerve VIII. Cranial CT scan often reveals a hypoplastic cochlea (81%) with absent semicircular canals in most cases. Hearing loss and difficulty with balance are the most common features associated with cochlear hypoplasia and absent semicircular canals. CHARGE syndrome is associated with characteristic external ears that tend to protrude and lack lobes. The hearing loss can range from a mild hearing loss to profound deafness. Hearing loss can be very difficult to measure in young children. Many children with CHARGE receive cochlear implants to aid their sensorineural hearing loss. Most also have balance problems (vestibular abnormalities) associated with absent semicircular canals, which is a key finding in making the diagnosis of CHARGE syndrome.

Most children with CHARGE have swallowing problems (cranial nerves IX/X). These swallowing problems include the inability to coordinate suck and swallow, leading to gagging and aspiration of food into the lungs (which can cause pneumonia). Many children require feeding via a gastrostomy tube (tube directly into the stomach through the abdominal wall) until they are able to swallow safely.

Many children with CHARGE have asymmetric facial palsy resulting in paralysis of one side of the face (cranial nerve VII). This results in a lack of facial expression, which is important when a child is working with teachers or therapists.

Most children with CHARGE have an absent or reduced sense of smell (cranial nerve I), which complicates learning to eat normally. Most patients with CHARGE syndrome have absent or abnormal olfactory bulbs in MRI, leading to a diminished sense of smell. Smell-testing can predict the presence of hypogonadotropic hypogonadism. The combination of defective olfaction (anosmia or hyposmia) with hypogonadotropic hypogonadism (termed Kallman syndrome) results in small external genitalia. This is very common in CHARGE syndrome and warrants consultation with an endocrinologist.

Choanal atresia
Choanae are the passages from the back of the nose to the throat that make it possible to breathe through the nose. In about half of all children with CHARGE, these passages may be blocked (atresia) or narrowed (stenosis). Among 12 patients with bilateral choanal atresia, 10 had related malformations, 3 of which had CHARGE syndrome. Surgery can often correct these defects. Patients with unilateral atresia can usually be corrected with 1 surgical procedure at a later age (median 6 years, range 6 months to 18 years), while patients with the bilateral form need a median of 2.85 interventions at an early age (median 25 days, range 6 days-6 years). If both sides are affected, immediate measures must be taken to allow the newborn to breathe properly and prevent respiratory failure.

Most children with CHARGE have unusual external ears. The “typical CHARGE ear” is short and wide with little or no earlobe. The helix (outer fold) may end abruptly in mid-ear. The center of the ear (concha) is often very triangular in shape. The ears are often floppy and may stick out due to weak cartilage. The two ears often look different from each other. There are also typical findings in the middle ear in CHARGE, including malformed bones of the middle ear (93%) and incomplete cochlea (Mondini defect), which is diagnosed with an MRI scan. In many cases, the external ear can be unique enough to suspect the diagnosis of CHARGE before examining other features, and a temporal bone CT scan to look for absent semicircular canals and evaluate the choanae for atresia or stenosis should prompt mutation analysis of CHD7 to confirm the diagnosis.

Minor Diagnostic Criteria:
Features less specific to CHARGE syndrome and/or not consistent enough to be considered major: heart defects, genital abnormalities, kidney abnormalities, cleft lip or palate, TE fistula or esophageal atresia, poor growth, hypotonia, typical CHARGE face, and typical CHARGE hand.

Heart defects
About 75-80% of children with CHARGE syndrome have congenital heart defects. Although all types of heart defects have been seen in children with CHARGE syndrome, the most common are tetralogy of Fallot (33%), VSD (ventricular septal defect), AV (atriventricular) canal defect, and aortic arch anomalies. The heart defects can range from an innocent murmur to life-threatening heart defects involving the outflow tracts of the heart. Most require medication and/or surgery. Severe heart defects are a major cause of death in children with CHARGE. The heart defects in CHARGE are similar to those seen in Deletion 22q11.2 syndrome.

Genital abnormalities
Most boys with CHARGE syndrome have a small penis, often with undescended testes (cryptorchidism). The urethral opening may not be at the end of the penis (hypospadias). Girls may have small labia. Among 46 boys with hypogonadotropic hypogonadism, 14 (30.4%) had Kallmann syndrome, 4 (8.7%) had CHARGE syndrome and 28 (60.9%) had hypogonadotropic hypogonadism without an olfaction deficit or olfactory bulb hypoplasia. Most children with CHARGE require hormone therapy to achieve puberty due to hypogonadotropic hypogonadism, and a pediatric endocrinologist should evaluate their pituitary gonadal axis.

Kidney abnormalities
About 40% of children with CHARGE syndrome have kidney abnormalities. These can include hydronephrosis (extra fluid in the kidneys) or reflux (backflow into the kidneys); horseshoe kidney; small or absent kidney; or multicystic dysplastic kidneys. All children with CHARGE should have a kidney ultrasound.

Cleft lip and/or cleft palate
About 25% of children with CHARGE have a cleft lip or cleft palate. The cleft lip can be one-sided or two-sided and may or not include the palate. A positive family history of any individual with an apparently isolated unilateral major CHARGE anomaly, or someone with a few of the minor features, should precipitate testing the affected child and both parents for CHD7. Some have cleft palate without cleft lip. Submucous cleft palate (just the muscle, not the bone in the roof of the mouth) may be hard to diagnose.

Tracheoesophageal Fistula/Esophageal atresia
About 15-20% of children with CHARGE are born with an esophageal atresia (EA), where the food pipe is not connected to the stomach or with tracheoesophageal fistula (TEF), where there is a connection between the windpipe (trachea) and the food pipe (esophagus). Both of these conditions require surgery. In addition, the trachea may be weak or floppy due to weak cartilage. This can complicate surgery to treat these conditions.

Poor growth
Although birth weight is usually normal, many children with CHARGE are small after birth. Sometimes this is due to nutrition problems, heart problems or multiple illnesses. Some children with CHARGE have growth hormone insufficiency, which can be evaluated with a growth hormone stimulation test.

Hypotonia of the trunk
Most children with CHARGE syndrome have upper body hypotonia (weakness). They are weak, especially in the trunk, and may have sloping shoulders. This weakness, especially combined with balance problems and/or vision problems, will delay walking. The average age of walking is about 3 or 4 years in children with CHARGE syndrome, and this results from the combination of hypotonia and diminished balance due to their underdeveloped semicircular canals.

Typical CHARGE face
Children with CHARGE syndrome often look similar to one another. The typical child has a square face, with broad prominent forehead, arched eyebrows, large eyes, occasional droopy eyelids, a prominent nasal bridge with square root, small nostrils, prominent nasal columella, flat midface, small mouth, occasional small chin, which improves with age. The face is often very asymmetric.

Typical CHARGE hand
Many children with CHARGE have a small thumb, broad palm with “hockey-stick” palmar crease, and short fingers.

Other Common Findings
These features may be important for management, but not very helpful in making the diagnosis. Brain abnormalities, including small head (microcephaly), enlarged cerebral ventricles or other abnormalities identified by brain imaging such as MRI or CT scan are occasionally seen. Apnea and seizures are rarely seen in children with CHARGE. Weak cartilage (as seen in the ears) can also affect the trachea (windpipe) making it weak. Sometimes the baby has a very weak cry due to laryngomalacia (weak vocal cords). A few children with CHARGE syndrome have missing or extra nipples. Some have a relatively wide neck, with occasional cervical vertebral abnormalities. Rarely, children with CHARGE have an umbilical hernia, omphalocele or limb abnormalities, such as abnormal thumbs or extra fingers.

A few children with CHARGE have DiGeorge sequence, consisting of a complex heart defect, immune deficiency, and abnormalities of the thyroid and parathyroid glands. Because these features are also seen in VCF, children with possible CHARGE and no mutation in CHD7 should have array comparative genomic hybridization testing done. Some children with CHARGE appear to have a poor immune response even, and the presence of hypocalcemia should prompt an immunologic evaluation. Most children with CHARGE syndrome and immunodeficiency have T-cell deficiency.

Many children with CHARGE develop scoliosis, even as relatively young children. This may be due in part to their weak upper body, but a skeletal survey should be carried out to exclude skeletal anomalies, particularly those of the cervical spine.

Developmental Features as Signs of CHARGE Syndrome
Most young children with CHARGE are developmentally delayed. Often, this is primarily due to sensory deficits (vision and/or hearing loss) and frequent illnesses and hospitalizations as infants and young children. Although developmentally delayed, many children with CHARGE will show significant catch up in later childhood, manifesting normal intellectual abilities, and ending up as independent adults. It is not possible to predict eventual development for any one child, and early intervention with a deaf-blind specialist is essential to remediate their sensory deficits and prevent behavioral problems. Regardless of the extent of inner ear anomalies and intellectual faculties, cochlear implantation with careful treatment planning can be a highly effective option for hearing rehabilitation in children with sensorineural hearing loss and CHARGE syndrome.

As children with CHARGE grow older, challenging behaviors can emerge. Some children display autistic-like behaviors such as hand waving or head banging. Often, these are attempts at communication by a child who has not yet developed language or other communication skills due to hearing and vision problems. These behaviors occur less often when a communication system (speech, signs, or a combination of both) is established. Older individuals with CHARGE may show signs of obsessive-compulsive disorder. Many children with CHARGE begin communication using sign language or some form of gestures and communication boards. Those with cochlear implants or hearing aids that bring hearing into the normal range will usually switch over to oral speech at some point. Learning signs first does not keep children from speaking later.

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The cause of CHARGE is usually a new mutation (change) in the CHD7 gene, or rarely, genomic alterations in the region of chromosome 8 (8q12.2) where the CHD7 gene is located. CHD7 function is required for the development of the retina and cranial motor neurons. Over 90 % of typical CHARGE patients have mutations in the CHD7 gene, while 65 %-70 % of all typical and suspected cases combined are demonstrate CHD7 mutations. The mutations are equally distributed along the coding region of CHD7 and most are nonsense or frameshift mutations. Pathogenic missense mutations are mainly present in the middle of the CHD7 gene, whereas benign variants are mainly clustered in the 5′ and 3′ regions. CHD7 missense mutations are, in general, associated with a milder phenotype than truncating mutations. Intragenic or promotor sequence complex genomic rearrangements can be missed by current sequencing without duplication/deletion or MLPA analysis. Most cases of CHARGE syndrome occur sporadically, often in association with older paternal age. In 12 out of 13 families, the mutation affected the paternal allele (92.3%), with a mean paternal age at birth of 32.92 years. In rare cases, CHARGE has run in families, either two affected children or a parent and child affected, either because of parental mosaicism for a CHD7 mutation, which results in a parent being mildly affected or not affected at all.

There are no known teratogens (exposures during pregnancy) that have been associated with CHARGE syndrome. Retinoic acid or isotretonin (a medicine taken for severe acne) can cause similar malformations when taken during the first trimester of pregnancy.

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Affected populations

CHARGE syndrome is a rare disorder, affecting 0.1-1.2/10,000 live births. It affects males and females in equal numbers and has been seen in all races and on every continent. There are far more cases of CHARGE than those described in the medical literature. Many cases are misdiagnosed or undiagnosed, especially in children with fewer problems. Although many features of CHARGE are apparent at birth, some features will not become apparent for weeks, months, or perhaps years later. The recurrence risk of CHARGE for parents with one affected child is low, around 2-3 percent. The recurrence risk for an adult with CHARGE to have an affected child may be as high as 50 percent.

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A medical geneticist or other specialist familiar with CHARGE syndrome should do a complete physical exam and order tests to look for the major and minor features of CHARGE listed above. Other similar disorders such as 22q11.2 deletion syndrome, Mowat-Wilson syndrome, Kabuki syndrome, Kallman syndrome, and EFTUD2 haploinsufficiency (multiple congenital anomalies/intellectual disability syndrome characterized by the association of mandibulofacial dysostosis with external ear malformations, hearing loss, cleft palate, choanal atresia, microcephaly, intellectual disability, esophageal atresia, congenital heart defects, and radial ray defects) need to be ruled out as well. Among 28 Mowat-Wilson syndrome patients with molecular confirmation of a ZEB2 mutation, 2 patients had clinical features of CHARGE syndrome (choanal atresia, coloboma, cardiac defects, genitourinary anomaly, and severe intellectual disability). Cases of Kabuki syndrome have presented with atypical features, consisting of bilateral microphthalmia, coloboma, anal atresia and panhypopituitarism, showing considerable phenotypic overlap with CHARGE syndrome. Mutations in the KMT2D gene, which encodes a H3K4 histone methyltransferase, are the major cause of Kabuki syndrome. Another patient, who was initially diagnosed with CHARGE syndrome (choanal hypoplasia, heart defect, anal atresia, vision problems and conductive hearing impairment), but sequencing and MLPA analysis of all coding exons of CHD7 revealed no pathogenic mutation, while sequence analysis of the KMT2D gene identified the heterozygous de novo nonsense mutation confirming a diagnosis of Kabuki syndrome. CHD7 and KMT2D function in the same chromatin modification machinery, providing a probable explanation for the phenotypic overlap between Kabuki and CHARGE syndromes.

Molecular Genetic testing is available for mutations in the CHD7 gene associated with the condition, and if this is negative, a SNP chromosomal microarray should be done, because in a few cases, there has been a submicroscopic genomic alteration of chromosome 8q12.2. If both these tests are negative, whole genome exome sequencing should be done, since other genetic disorders share some clinical features with CHARGE syndrome, and de novo mutations in ZEB2, KMT2D and EFTUD2 have been detected in children previously diagnosed as having CHARGE syndrome.

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Standard Therapies

Although these children have many problems, they can survive and become healthy, happy citizens. Many of the structural abnormalities (choanal atresia, heart defects, cleft lip, etc.) can be surgically corrected. Others, such as feeding problems and speech and language deficits may require years of therapy and other interventions. Infants diagnosed with CHARGE syndrome will need to be followed by a number of medical and developmental specialists, depending on their individual needs. Some of the medical specialists who often follow children with CHARGE syndrome include genetics, cardiology, audiology and ENT, ophthalmology, urology, and endocrinology.

More than 50% of children with CHARGE syndrome experience sleep disturbances, and obstructive sleep apnea appears to be prevalent in children with CHARGE syndrome. All conventional treatments for obstructive sleep apnea reduce symptoms. Botulinum toxin A (Botox) has been used to reduce excess salivary secretions in a ventilator-dependant infant with CHARGE syndrome who would have required a tracheotomy. Venous anomalies of the temporal bone were present in 10 of 18 (56%) patients with CHARGE syndrome. The pattern of venous abnormality suggests that there is a failure of the sigmoid sinus/jugular bulb to fully develop, resulting in persistence of emissary veins. Recognition of these abnormal venous structures during otologic surgery is critical to avoiding potentially catastrophic bleeding.

Analysis of CHD7 in 12 patients with semicircular canal dysplasia and variable clinical features of CHARGE syndrome revealed 6 CHD7 mutations, 5 of which occurred in patients who fulfilled diagnostic criteria for typical CHARGE syndrome, and three of which were previously undiagnosed. Among 7 children with CHARGE and congenital profound hearing loss, all had hypoplastic or absent auditory nerves, affecting their outcomes with cochlear implants. Of 30 ears evaluated with CT, 28 (93%) had major abnormalities of the inner ear including hypoplasia or aplasia of the semicircular canals and abnormalities of the cochlea and vestibule. CT imaging revealed cochlear aperture narrowing or occlusion in 16 ears, one of which had normal hearing. Among 8 patients with profound sensorineural hearing loss who underwent magnetic resonance imaging 13 of 14 ears were noted to have absent or deficient cochlear nerves. Because of the implications of cochlear nerve deficiency in therapeutic decision-making regarding cochlear implantation, MRI evaluation of the eighth nerve should be considered in CHARGE patients with profound sensorineural hearing loss. In patients with markedly abnormal middle ear anatomy, CT image guided surgery was helpful. These children were offered a bilingual early intervention approach, using sign language and verbal language, to ensure best language outcomes. Children with CHARGE syndrome and progressive profound hearing loss did well with cochlear implants and continued to use verbal language. Numerous patients have undergone cochlear implantation, with most patients demonstrating favorable outcomes. Larger diameter of the cochleovestibular nerve on imaging and absence of severe intellectual disability were factors related to better outcomes after cochlear implantation, rather than the type of CHD7 mutations. Auditory brainstem implantation may be a viable option in patients with CHARGE syndrome who have failed to benefit from cochlear implantation.

A novel mouse model of CHD7 dysfunction, termed Looper, harbors a nonsense mutation within the Chd7 gene. Looper mice exhibit growth retardation, facial asymmetry, vestibular defects, eye anomalies, hyperactivity, ossicle malformation, hearing loss and vestibular dysfunction. Chd7 also regulates genes involved in neural crest cell guidance, demonstrating a significant role in the pathogenesis of CHARGE syndrome. Mice with heterozygous Chd7 mutations exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis. Chd7 is highly expressed in mature inner and outer hair cells, spiral ganglion neurons, vestibular sensory epithelia and middle ear ossicles.

Among 202 patients with CHD7 mutations and CHARGE syndrome, a wide range of heart defects in 74% this cohort of patients. Conotruncal defects and atrioventricular septal defects were over-represented in patients with CHD7 mutations compared with patients with non-syndromic heart defects. However, CHD7 mutations are not a major cause of atrioventricular septal and conotruncal heart defects. Work with mouse models demonstrate that CHD7 plays an important role in the cardiogenic mesoderm during cardiovascular development.

Among 25 patients with CHARGE syndrome, 76% of subjects had some type of endocrine disorder: short stature (72%), hypogonadotropic hypogonadism (60%), hypothyroidism (16%), and combined hypopituitarism (8%). A mutation in CHD7 was found in 80% of these subjects. Analysis of growth in 19 children with CHARGE syndrome, revealed a significant loss of median body length, at around 4 weeks of age from -0.5 to -2.3 standard deviations (SDS). At 1 year, the median length was -2.6 SDS and it remained low until 5 years of age when the lowest value was found to be -2.8 SDS. There was a significant increase in median body mass index (BMI) from -1.15 SDS at 1 year to -0.15 SDS at 5 years. Children with CHARGE syndrome displayed almost normal length and weight data at birth, with just one of the 19 infants having below average length for gestational age. Among 16 children with CHARGE syndrome, short stature, and decreased levels of serum growth hormone (GH), conventional doses of GH had a positive effect on short-term growth velocity without any safety issues or adverse effect on BMI. At the start of GH therapy, height was -3.6 SDS and after 2.7 years of GH therapy, height increased to -2.2 SDS in these patients with CHARGE syndrome. Hormonal management also helps treat symptoms of hypogonadism. Among 209 Kallman syndrome patients who had not been diagnosed with CHARGE syndrome, mutations in CHD7 were found in 24 patients (11.5%). Among 783 patients with isolated gonadotropin-releasing hormone deficiency lacking full CHARGE features, CHD7 variants were found in 5.2% of this cohort (73% missense and 27% splice variants), of which 75% were deleterious. Chd7 mutant mouse embryos have CHD7 dosage-dependent reductions in expression levels of Fgfr1, Bmp4 and Otx2 in the olfactory placode suggesting that that CHD7 plays a critical role in the development and maintenance of gonadotropin-releasing hormone neurons for regulating puberty and reproduction.

Others involved in the treatment of children with CHARGE include deaf/blind specialists, occupational therapy, physical therapy and speech therapy. Appropriate therapies and educational interventions must take into account any hearing and vision loss, which is present. The intelligence of children with CHARGE is often underestimated due to the combined hearing and vision problems. A deaf/blind specialist (not just a vision specialist and a hearing specialist) is critical for any child with someone with both vision loss and some hearing loss.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive. A team approach is essential for these complex children.

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Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

For information about clinical trials sponsored by private sources, contact:

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Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder (e.g., visual handicaps, heart disease, short stature, etc.)

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Acanfora MM, Stirnemann J, Marchitelli G, et al. Ultrasound evaluation of development of olfactory sulci in normal fetuses: a possible role in diagnosis of CHARGE syndrome. Ultrasound Obstet Gynecol. 2016 Aug;48(2):181-184.

Ahn JH, Lee KS. Outcomes of cochlear implantation in children with CHARGE syndrome. Acta Otolaryngol. 2013;133:1148-1153.

Anderzén-Carlsson A. CHARGE Syndrome-a five case study of the syndrome characteristics and health care consumption during the first year in life. J Pediatr Nurs. 2015;30:6-16.

Badalato L, Farhan SM, Dilliott AA, et al. KMT2D p.Gln3575His segregating in a family with autosomal dominant choanal atresia strengthens the Kabuki/CHARGE connection. Am J Med Genet A. 2017 Jan;173(1):183-189.

Balasubramanian R, Choi JH, Francescatto L, et al. Functionally compromised CHD7 alleles in patients with isolated GnRH deficiency. Proc Natl Acad Sci U S A. 2014;111:17953-17958.

Balasubramanian R, Crowley WF Jr. Reproductive endocrine phenotypes relating to CHD7 mutations in humans. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):507-515.

Basson MA, van Ravenswaaij-Arts C. Functional insights into chromatin remodelling from studies on CHARGE syndrome. Trends Genet. 2015;31:600-611.

Bergman JE, Janssen N, van der Sloot AM, et al. A novel classification system to predict the pathogenic effects of CHD7 missense variants in CHARGE syndrome. Hum Mutat. 2012;33:1251-1260.

Bergman JE, de Ronde W, Jongmans MC, et al. The results of CHD7 analysis in clinically well-characterized patients with Kallmann syndrome. J Clin Endocrinol Metab. 2012;97:E858-862.

Bilan F, Legendre M, Charraud V, et al. Complete screening of 50 patients with CHARGE syndrome for anomalies in the CHD7 gene using a denaturing high-performance liquid chromatography-based protocol: new guidelines and a proposal for routine diagnosis. J Mol Diagn. 2012;14:46-55.

Birman CS, Brew JA, Gibson WP, Elliott EJ. CHARGE syndrome and Cochlear implantation: difficulties and outcomes in the paediatric population. Int J Pediatr Otorhinolaryngol. 2015;79:487-492.

Blake KD, Hudson AS. Gastrointestinal and feeding difficulties in CHARGE syndrome: A review from head-to-toe. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):496-506.

Blake K, Davenport SH, Hall BD,et al. CHARGE Association – An update and review for the primary pediatrician. Clinical Pediatrics. 1998;37:159-174.

Blustajn J, Kirsch CFE, Panigrahy A, Netchine I. Olfactory anomalies in CHARGE syndrome: imaging findings of a potential major diagnostic criterion. Am J Neuroradiol. 2008;29:1266-1269.

Blake KD, MacCuspie J, Corsten G. Botulinum toxin injections into salivary glands to decrease oral secretions in CHARGE syndrome: prospective case study. Am J Med Genet A. 2012;158A:828-831.

Butcher DT, Cytrynbaum C, Turinsky AL, et al. CHARGE and Kabuki Syndromes: Gene-Specific DNA Methylation Signatures Identify Epigenetic Mechanisms Linking These Clinically Overlapping Conditions. Am J Hum Genet. 2017 May 4;100(5):773-788.

Cardoso CC, Sales de Meneses M, Silva IM, Alves AM. Cochlear Implants in Children Diagnosed with CHARGE Syndrome. Int Arch Otorhinolaryngol. 2013;17:424-428.

Corsten-Janssen N, du Marchie Sarvaas GJ, Kerstjens-Frederikse WS, et al. CHD7 mutations are not a major cause of atrioventricular septal and conotruncal heart defects. Am J Med Genet A. 2014;164A:3003-3009.

Corsten-Janssen N, Kerstjens-Frederikse WS, du Marchie Sarvaas GJ, et al. The cardiac phenotype in patients with a CHD7 mutation. Circ Cardiovasc Genet. 2013;6:248-254.

Corsten-Janssen N, Scambler PJ. Clinical and molecular effects of CHD7 in the heart. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):487-495.

Corsten-Janssen N, Saitta SC, Hoefsloot LH, et al. More clinical overlap between 22q11.2 deletion syndrome and CHARGE syndrome than often anticipated. Mol Syndromol. 2013;4:235-245.

Corsten-Janssen N, van Ravenswaaij-Arts CMA, Kapusta L. Congenital arch vessel anomalies in CHARGE syndrome: A frequent feature with risk for co-morbidity. Int J Cardiol Heart Vasc. 2016 May 25;12:21-25.

de Geus CM, Free RH, Verbist BM, et al. Guidelines in CHARGE syndrome and the missing link: Cranial imaging. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):450-464.

Delahaye A, Sznajer Y, Lyonnet S, et al. Familial CHARGE syndrome because of CHD7 mutation: clinical intra- and interfamily variability. 2007;72:112-121.

Dörr HG, Boguszewski M, Dahlgren J, et al. Short children with CHARGE syndrome: Do they benefit from growth hormone therapy? Horm Res Paediatr. 2015;84:49-53.

Dörr HG, Madeja J, Junghans C. Spontaneous postnatal growth is reduced in children with CHARGE syndrome. Acta Paediatr. 2015;104:e314-318.

Esposito A, Tufano M, Di Donato I, et al. Effect of long-term GH treatment in a patient with CHARGE association. Ital J Pediatr. 2014;40:51.

Friedmann DR, Amoils M, Germiller JA, et al. Venous malformations of the temporal bone are a common feature in CHARGE syndrome. Laryngoscope. 2012;122:895-900.

Graham, JM Jr, Rosner B, Dykens E, Visootsak J. Behavioral features of CHARGE syndrome (Hall-Hittner syndrome): comparison with Down syndrome, Prader-Willi syndrome and Williams syndrome. American Journal of Medical Genetics. 2005;133A: 240-247.

Graham JM Jr. A recognizable syndrome within CHARGE association: Hall-Hittner syndrome. Am J Med Genet. 2005;99:120-123.

Gregory LC, Gevers EF, Baker J, et al. Structural pituitary abnormalities associated with CHARGE syndrome. J Clin Endocrinol Metab. 2013;98:E737-743.

Green GE, Huq FS, Emery SB, et al. CHD7 mutations and CHARGE syndrome in semicircular canal dysplasia. Otol Neurotol. 2014;35:1466-1470.

Ha J, Ong F, Wood B, Vijayasekaran S. Radiologic and Audiologic Findings in the Temporal Bone of Patients with CHARGE Syndrome. Ochsner J. 2016 Summer;16(2):125-129.

Hale CL, Niederriter AN, Green GE, Martin DM. Atypical phenotypes associated with pathogenic CHD7 variants and a proposal for broadening CHARGE syndrome clinical diagnostic criteria. Am J Med Genet A. 2016 Feb;170A(2):344-354.

Hall BD. Choanal atresia and associated multiple anomalies. J Pediatr. 1979;95:395-398.

Hartshorne N, Hudson A, MacCuspie J, et al. Quality of life in adolescents and adults with CHARGE syndrome. Am J Med Genet A. 2016 Aug;170(8):2012-2021.

Hartshorne TS, Stratton KK, Brown D, et al. Behavior in CHARGE syndrome. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):431-438.

Hefner MA, Fassi E. Genetic counseling in CHARGE syndrome: Diagnostic evaluation through follow up. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):407-416.

Hittner HM, Hirsch NJ, Kreh GM, Rudolph AJ. Colobomatous microphthalmia, heart disease, hearing loss, and mental retardation: a syndrome. J Pediatr Ophthalmol Strabismus. 1979;16:122-128.

Hoch MJ, Patel SH, Jethanamest D, et al. Head and Neck MRI Findings in CHARGE Syndrome. AJNR Am J Neuroradiol. 2017 Dec;38(12):2357-2363.

Holcomb MA, Rumboldt Z, White DR. Cochlear nerve deficiency in children with CHARGE syndrome. Laryngoscope. 2013;123:793-796.

Hsu P, Ma A, Barnes EH, et al. The Immune Phenotype of Patients with CHARGE Syndrome. J Allergy Clin Immunol Pract. 2016 Jan-Feb;4(1):96-103.e2.

Hsu P, Ma A, Wilson M, et al. CHARGE syndrome: a review. J Paediatr Child Health. 2014 Jul;50(7):504-511.

Hudson A, Macdonald M, Friedman JN, Blake K. CHARGE syndrome gastrointestinal involvement: from mouth to anus. Clin Genet. 2017 Jul;92(1):10-17.

Hughes SS, Welsh HI, Safina NP, et al. Family history and clefting as major criteria for CHARGE syndrome. Am J Med Genet A. 2014;164A:48-53.

Hurd EA, Adams ME, Layman WS, et al. Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in a mouse model of CHARGE syndrome. Hear Res. 2011;282:184-195.

Husu E, Hove HD, Farholt S, et al. Phenotype in 18 Danish subjects with genetically verified CHARGE syndrome. Clin Genet. 2013;83:125-134.

Inchingolo F, Pacifici A, Gargari M, et al. CHARGE syndrome: an overview on dental and maxillofacial features. Eur Rev Med Pharmacol Sci. 2014;18:2089-2093.

Isaac KV, Ganske IM, Rottgers SA, et al. Cleft Lip and Palate in CHARGE Syndrome: Phenotypic Features That Influence Management. Cleft Palate Craniofac J. 2018 Mar;55(3):342-347.

Issekutz KA, Graham JM Jr., Prasad C, et al. The incidence and prevalence of CHARGE association/syndrome in Canada: initial results from a population-based study. American Journal of Medical Genetics. 2005;133A:309-317.

Janssen N, Bergman JE, Swertz MA, et al. Mutation update on the CHD7 gene involved in CHARGE syndrome. Hum Mutat. 2012;33:1149-1160.

Jongmans MC, Admiraal RJ, van der Donk KP, et al. CHARGE syndrome: The phenotypic spectrum of mutations in the CHD7 gene. J Med Genet. 2006;43:306-314.

Jongmans MCJ, Hoefsloot LH, van der Donk KP et al. Familial CHARGE syndrome and the CHD7 gene: A recurrent missense mutation, intrafamilial recurrence and variability. Am J Med Genet Part A. 2008;146A:43-50.

Jyonouchi S, McDonald-McGinn D, Bale S, Zachai E, Sullivan KE: CHARGE (coloboma, heart defect, atresia choanae,retarded growth and development, genital hypoplasia, ear anomslies/deafness) syndrome and chromosome 22q11.2 deletion syndrome: a comparison of immunologic and nonimmunologic phenotypic features. Pediatrics. 2009;123:e871-e877.

Komatsuzaki KM, Shimomura S, Tomishima Y, et al. Progressing subglottic and tracheobronchial stenosis in a patient with CHARGE syndrome diagnosed in adulthood. Respir Med Case Rep. 2014;12:24-26.

Kong F, Martin DM. Atopic disorders in CHARGE syndrome: A retrospective study and literature review. Eur J Med Genet. 2018 Apr;61(4):225-229.

Lalani SR, Safiullah AA, Fernbach SD, et al. Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation. American Journal of Human Genetics. 2006;78:303-314.

Layman WS, Hurd EA, Martin DM.Reproductive dysfunction and decreased GnRH neurogenesis in a mouse model of CHARGE syndrome. Hum Mol Genet. 2011;20:3138-3150.

Lehalle D, Gordon CT, Oufadem M, et al. Delineation of EFTUD2 haploinsufficiency-related phenotypes through a series of 36 patients. Hum Mutat. 2014;35:478-485.

Lasserre E, Vaivre-Douret L, Abadie V. Psychomotor and cognitive impairments of children with CHARGE syndrome: common and variable features. Child Neuropsychol. 2013;19:449-465.

Legendre M, Abadie V, Attié-Bitach T, et al. Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE syndrome. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):417-430.

Macdonald M, Hudson A, Bladon A, et al. Experiences in feeding and gastrointestinal dysfunction in children with CHARGE syndrome. Am J Med Genet A. 2017 Nov;173(11):2947-2953.

Mahdi ES, Whitehead MT. Clival Malformations in CHARGE Syndrome. AJNR Am J Neuroradiol. 2018 Jun;39(6):1153-1156.

Manica D, Schweiger C, Netto CC, Kuhl G. Retrospective study of a series of choanal atresia patients. Int Arch Otorhinolaryngol. 2014;18:2-5.

Marcos S, Sarfati J, Leroy C, et al. The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients. J Clin Endocrinol Metab. 2014;99:E2138-143.

Mehr S, Hsu P, Campbell D. Immunodeficiency in CHARGE syndrome. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):516-523.

Morimoto AK, Wiggins RH, Hudgins PA, et al. Absent semicircular canals in CHARGE syndrome: radiologic spectrum of findings. Am J Neuroradiol. 2006;27:1663-1671.

Nishina S, Kosaki R, Yagihashi T, et al. Ophthalmic features of CHARGE syndrome with CHD7 mutations. Am J Med Genet A. 2012;158A:514-518.

Ogier JM, Carpinelli MR, Arhatari BD, et al. CHD7 deficiency in “Looper”, a new mouse model of CHARGE syndrome, results in ossicle malformation, otosclerosis and hearing impairment. PLoS One. 2014;9:e97559.

Pagon RA, Graham JM Jr, Zonana J, et al. Congenital heart disease and choanal atresia with multiple anomalies. J Pediatr. 1981;99:223-227.

Payne S, Burney MJ, McCue K, et al. A critical role for the chromatin remodeller CHD7 in anterior mesoderm during cardiovascular development. Dev Biol. 2015;405:82-95.

Pauli S, von Velsen N, Burfeind P, et al. CHD7 mutations causing CHARGE syndrome are predominantly of paternal origin. Clin Genet. 2012;81:234-239.

Pisaneschi E, Sirleto P, Lepri FR, et al. CHARGE syndrome due to deletion of region upstream of CHD7 gene START codon. BMC Med Genet. 2015;16:78.

Ricci G, Trabalzini F, Faralli M, et al. Cochlear implantation in children with “CHARGE syndrome”: surgical options and outcomes. Eur Arch Otorhinolaryngol. 2014;271:489-493.

Sanlaville D, Etchevers HC, Gonzales M, et al. Phenotypic spectrum of CHARGE syndrome in fetuses with CHD7 truncating mutations correlates with expression during human development. J Med Genet. 2006;43:211-217.

Sanlaville D, Verloes A. CHARGE syndrome: an update. Europ J Hum Genet. 2007;15:389-399.

Santoro L, Ficcadenti A, Zallocco F, et al. Cognitive-motor profile, clinical characteristics and diagnosis of CHARGE syndrome: an Italian experience. Am J Med Genet A. 2014;164A:3042-3051.

Searle LC, Graham JM Jr, Prasad C, Blake KD. CHARGE syndrome from birth to adulthood: an individual reported on from 0 to 33 years. American Journal of Medical Genetics. 2005;133A:344-349.

Shoji Y, Ida S, Etani Y, et al. Endocrinological Characteristics of 25 Japanese Patients with CHARGE Syndrome. Clin Pediatr Endocrinol. 2014;23:45-51.

Schulz Y, Freese L, Mänz J, et al. CHARGE and Kabuki syndromes: a phenotypic and molecular link. Hum Mol Genet. 2014;23:4396-4405.

Schulz Y, Wehner P, Opitz L, et al. CHD7, the gene mutated in CHARGE syndrome, regulates genes involved in neural crest cell guidance. Hum Genet. 2014;133:997-1009.

Sohn YB, Ko JM, Shin CH, et al. Cerebellar vermis hypoplasia in CHARGE syndrome: clinical and molecular characterization of 18 unrelated Korean patients. J Hum Genet. 2016 Mar;61(3):235-239.

Song MH, Cho HJ, Lee HK, et al. CHD7 mutational analysis and clinical considerations for auditory rehabilitation in deaf patients with CHARGE syndrome. PLoS One. 2011;6(9):e24511. doi: 10.1371/journal.pone.0024511. Epub 2011 Sep 13.

Sperry ED, Hurd EA, Durham MA, et al. The chromatin remodeling protein CHD7, mutated in CHARGE syndrome, is necessary for proper craniofacial and tracheal development. Dev Dyn. 2014;243:1055-1066.

Trevisi P, Ciorba A, Aimoni C, et al. Outcomes of long-term audiological rehabilitation in CHARGE syndrome. Acta Otorhinolaryngol Ital. 2016 Jun;36(3):206-214.

Trider CL, 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 Mar;173(3):684-691.

Trider CL, Corsten G, Morrison D, et al. Understanding obstructive sleep apnea in children with CHARGE syndrome. Int J Pediatr Otorhinolaryngol. 2012;76:947-953.

Vatta M, Niu Z, Lupski JR, et al. Evidence for replicative mechanism in a CHD7 rearrangement in a patient with CHARGE syndrome. Am J Med Genet A. 2013;161A:3182-3186.

Verhagen JM, Oostdijk W, Terwisscha van Scheltinga CE, et al. An unusual presentation of Kabuki syndrome: clinical overlap with CHARGE syndrome. Eur J Med Genet. 2014;57:510-512.

Verloes A. Updated diagnostic criteria for CHARGE syndrome: a proposal. Am J Med Genet A. 2005;133:306-308.

Vesseur A, Free R, Langereis M, et al. Suggestions for a Guideline for Cochlear Implantation in CHARGE Syndrome. Otol Neurotol. 2016 Oct;37(9):1275-1283.

Vesseur A, Langereis M, Free R, et al. Influence of hearing loss and cognitive abilities on language development in CHARGE Syndrome. Am J Med Genet A. 2016 Aug;170(8):2022-2030.

Vesseur AC, Verbist BM, Westerlaan HE, et al. CT findings of the temporal bone in CHARGE syndrome: aspects of importance in cochlear implant surgery. Eur Arch Otorhinolaryngol. 2016 Dec;273(12):4225-4240.

Vincenti V, Di Lella F, Falcioni M et al. Cochlear implantation in children with CHARGE syndrome: a report of eight cases. Eur Arch Otorhinolaryngol. 2018 Aug;275(8):1987-1993.

Vissers LE, van Ravenswaaij CM, Admiraal R, et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004;36:955-957.

Vizeneux A, Hilfiger A, Bouligand J, et al. Congenital hypogonadotropic hypogonadism during childhood: presentation and genetic analyses in 46 boys. PLoS One. 2013;8:e77827.

Wenger TL, Harr M, Ricciardi S, et al. CHARGE-like presentation, craniosynostosis and mild Mowat-Wilson Syndrome diagnosed by recognition of the distinctive facial gestalt in a cohort of 28 new cases. Am J Med Genet A. 2014;164A:2557-2566.

Wen J, Pan L, Xu X, et al. Clinical data and genetic mutation in Kallmann syndrome with CHARGE syndrome: Case report and pedigree analysis. Medicine (Baltimore). 2018 Jul;97(27):e11284.

Whittaker DE, Kasah S, Donovan APA, et al. Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome. Am J Med Genet C Semin Med Genet. 2017 Dec;175(4). doi: 10.1002/ajmg.c.31595. Epub 2017 Nov 23.

Wineland A, Menezes MD, Shimony JS, et al. Prevalence of Semicircular Canal Hypoplasia in Patients With CHARGE Syndrome: 3C Syndrome. JAMA Otolaryngol Head Neck Surg. 2017 Feb 1;143(2):168-177.

Wong MT, Schölvinck EH, Lambeck AJ, van Ravenswaaij-Arts CM. CHARGE syndrome: a review of the immunological aspects. Eur J Hum Genet. 2015;23:1451-1459.

Xu C, Cassatella D, van der Sloot AM, et al. Evaluating CHARGE syndrome in congenital hypogonadotropic hypogonadism patients harboring CHD7 variants. Genet Med. 2017 Nov 16. doi: 10.1038/gim.2017.197. [Epub ahead of print]

Young NM, Tournis E, Sandy J, et al. Outcomes and Time to Emergence of Auditory Skills After Cochlear Implantation of Children With Charge Syndrome. Otol Neurotol. 2017 Sep;38(8):1085-1091.

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. CHARGE Syndrome; Entry No: 214800. Last Edited August 31, 2016. Available at: http://omim.org/entry/214800 Accessed July 21, 2018.

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