Clinical utility gene card for: CHARGE syndrome - update 2015

Ravenswaaij-Arts, Conny M. A. van; Blake, Kim; Hoefsloot, Lies H.; Verloès, Alain

doi:10.1038/ejhg.2015.15

Cited by 22 publications

(26 citation statements)

References 20 publications

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“…It is now well established that individuals with CHARGE display a wide spectrum of pleiotropic phenotypes, which have resulted in the definition of ‘major’ and ‘minor’ clinical criteria for clinical diagnosis of this developmental disorder (Hale et al 2016; Jongmans et al 2006). The letter “ G ” in the CHARGE acronym refers to gonadal defects which represents one of the four minor diagnostic criteria that clinically defines CHARGE syndrome (van Ravenswaaij-Arts et al 2015). The gonadal defects in CHARGE were initially recognized in male infants who displayed genital hypoplasia characterized by micropenis and/or cryptorchidism (Pagon et al 1981).…”

Section: Introductionmentioning

confidence: 99%

Reproductive endocrine phenotypes relating to CHD7 mutations in humans

Balasubramanian

Crowley

2017

American J of Med Genetics Pt C

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Mutations in the gene CHD7 cause CHARGE syndrome, a rare multi-organ syndromic disorder. Gonadal defects are common in individuals with CHARGE syndrome (seen in ~60–80% of cases) and represent the letter “G” in the CHARGE syndrome acronym. The gonadal defect in CHARGE syndrome results from congenital deficiency of the hypothalamic hormone Gonadotropin-releasing hormone (GnRH), which manifests clinically as pubertal failure and infertility, and biochemically as hypogonadotropic hypogonadism (low sex steroid hormone levels with inappropriately normal or low gonadotropin levels). In addition to the gonadal endocrine abnormalities, in a small minority of individuals with CHARGE, additional endocrine defects including growth hormone deficiency, multiple pituitary hormone deficits and primary hypothyroidism may also be seen. CHD7 mutations disrupt the targeting of olfactory axons and the migration of GnRH-synthesizing neurons during embryonic development, resulting in congenital idiopathic hypogonadotropic hypogonadism (IHH) and anosmia (or hyposmia), two features that define human Kallmann syndrome. Since Kallmann syndrome is as one of its constituent phenotypes in individuals with CHARGE, recent studies have investigated the role of CHD7 mutations in individuals with IHH and established that deleterious missense mutations in CHD7 are associated with Kallmann syndrome as well as normosmic form of IHH. These missense mutations affect the ATPase and nucleosome remodeling activities of the CHD7 protein. These observations suggest that CHD7 protein function is critical for the ontogeny of GnRH neurons and neuroendocrine regulation of GnRH secretion.

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Section: Introductionmentioning

confidence: 99%

Reproductive endocrine phenotypes relating to CHD7 mutations in humans

Balasubramanian

Crowley

2017

American J of Med Genetics Pt C

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“…The pathophysiology underlying the common GI and feeding problems in CHARGE syndrome is still not completely understood. CHARGE syndrome is mainly caused by a mutation in the CHD7 gene, which codes a chromodomain helicase DNA binding protein . This causes a disruption in the chromatin remodeling and its important regulation of gene expression in embryogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Feeding difficulties are most often present from day one of life, due to complex anatomical malformations including cardiovascular anomalies, cleft lip and palate, tracheaesophageal fistula, laryngeal malformations, choanal atresia and stenosis, and extensive cranial nerve dysfunction . Introduction of oral feeding is often delayed due to these anatomical abnormalities interfering with both oral motor skills and respiration .…”

Section: Discussionmentioning

confidence: 99%

CHARGE syndrome gastrointestinal involvement: from mouth to anus

et al. 2017

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CHARGE syndrome is an autosomal dominant disorder that occurs as a result of a heterozygous loss-of-function mutation in the chromodomain helicase DNA-binding (CHD7) gene, which is important for neural crest cell formation. Gastrointestinal (GI) symptoms and feeding difficulties are highly prevalent but are often a neglected area of diagnosis, treatment, and research. Cranial nerve dysfunction, craniofacial abnormalities, and other physical manifestations of this syndrome lead to gut dysmotility, sensory impairment, and oral-motor function abnormalities. Over 90% of children need tube feeding early in their life and many experience weak sucking/chewing, gastroesophageal reflux disease (GERD), and aspiration. The mainstay of treatment thus far has consisted of feeding therapy, GERD medications, Nissen fundoplication, gastrostomy/jejunostomy, and food texture limitation. Owing to the multitude of severe medical issues associated with this genetic disorder, GI involvement is often overlooked. Here, we report on five patients with CHARGE syndrome who manifested a range of severe GI and feeding difficulties.

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“…CHARGE syndrome (CS) (OMIM #214800) is an autosomal dominant condition with an occurrence of 1 in 10,000 births [1,2]. The clinical features of CS were originally described in 1979 by Hall and Hittner [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…The condition is typically sporadic with few familial cases reported [7,12]. It has a considerable phenotypic variability [2] with no single feature being consistently present and, for this reason, it represents a diagnostic challenge for the primary care physician. Here we report eight different cases of CS whose diagnosis was made early in life.…”

Section: Introductionmentioning

confidence: 99%

A case series of CHARGE syndrome: identification of key features for a neonatal diagnosis

et al. 2020

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Background: An early diagnosis of CHARGE syndrome is challenging, especially for the primary care physicians who often take care of neonates with multiple congenital anomalies. Here we report eight cases of CHARGE syndrome whose diagnosis was made early in life with the intent to identify the most helpful features allowing a prompt clinical diagnosis. Methods: Medical records of patients with CHARGE syndrome whose diagnosis was made at the Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico in Milan, Italy were retrospectively reviewed. Results: Taken together, these patients reflect the considerable phenotypic variability of the syndrome; in one patient, the diagnosis was made immediately after birth because all the major criteria were met. In six patients, presenting with relatively nonspecific defects, a temporal bone computerized tomography scan was essential to achieve the correct diagnosis. In one patient, the diagnosis was made later than the others were. A careful examination revealed the presence of outer, middle, and inner ear anomalies: these elements, in the absence of any additional major criteria, represented for us an important diagnostic clue. Conclusions: This article suggests that an accurate evaluation of the ear should be made every time CHARGE syndrome is considered as a likely diagnosis even when the standard criteria are not fulfilled.

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Clinical utility gene card for: CHARGE syndrome - update 2015

Cited by 22 publications

References 20 publications

Reproductive endocrine phenotypes relating to CHD7 mutations in humans

Reproductive endocrine phenotypes relating to CHD7 mutations in humans

CHARGE syndrome gastrointestinal involvement: from mouth to anus

A case series of CHARGE syndrome: identification of key features for a neonatal diagnosis

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