Margaret A. Hefner

The spectrum of clinical features in CHARGE syndrome

Fifteen patients with CHARGE syndrome are described, nine sporadic and six familial. A recognizable pattern of malformations is present which appears to constitute a syndrome rather than a non‐random association. In addition to acronymic features of Coloboma, ifeart disease, Atresia of the choanae,.Retarded growth and development, Genital hypoplasia, and Ear anomalies, other important diagnostic features include facial paralysis and feeding problems suggestive of velopharyngeal incompetency. A square facial appearance with asymmetry and malar flattening is characteristic, and long philtrum or prominent nasal columella may be present. Characteristic external ear anomalies and a ‘wedge’‐shaped audiogram may be unique to this syndrome. Short stature and hypogonadism with genital hypoplasia is pituitary or possibly hypothalamic in origin. Each feature varies from normal to severe involvement including mental function, and no single feature appears to be necessary for diagnosis.

Dominant Charge association

We had the opportunity to examine eight individuals in four generations of a family with dominant CHARGE association. In three generations there were five affected individuals. The 25-year old male proband had coloboma of the iris, retina and optic disc, mental retardation, hypogonadism, malformed ears, and mixed hearing loss. His 19-year old sister had colobomas of the retina, choroid, and disc, mental retardation and malformed ears. The mother of these two individuals had coloboma of the retina, choroid, and optic disc, dull mentality, and mixed hearing loss. The probands maternal grandmother had peripapillary staphylomatous changes of the disc, mixed hearing loss, and malformed protruding ears. The probands maternal uncle had mental retardation, hypogonadism, mixed hearing loss, protruding ears, but no colobomas. All of the affected individuals had a distinct configuration to the midface, including malar hypoplasia, prominent nasal columnella and a long nasal philtrum. The inheritance of the CHARGE association in this family would appear to be autosomal dominant. However, as the males have not reproduced, it is not possible to rule out X-linked dominant inheritance.

CHARGE Syndrome. Part II. Hearing loss

CHARGE is a mnemonic for a syndrome with multiple congenital anomalies that occurs with normal chromosomes. The unique external ear anomalies have been described in CHARGE Syndrome Part I in this journal. This report describes the distinctive middle ear and sensorineural losses that occur in the syndrome, both of which can be progressive and, in most cases, are moderate to severe. There is evidence to indicate that these losses are due to congenital ossicular anomalies, eustachian tube dysfunction from craniofacial malformation, and cochlear involvement that is greatest for high frequencies.

Use of an expert model to test diagnostic criteria in CHARGE syndrome

AI/GEN is an expert model of the diagnosis of deaf-blind syndromes that uses the EXPERT system developed by Rutgers University. Its knowledge structure employs criteria tables for diagnosis of the three types of CHARGE syndrome. The system has been used to test the published diagnostic criteria against the revised expert criteria, the latter being significantly more accurate than the former. The two sets of criteria are also compared with respect to the specificity and sensitivity of diagnosis. Expert systems can be of direct use to experts in refining and revising their diagnostic criteria.