CHARGE syndrome

Findings

Posterior orbital globe defects of bilateral colobomas (Figure 1).
Bilateral choanal atresia, predominantly osseous component (Figure 2). Notice the bilateral air-fluid levels within the nasal cavity, which is classic for choanal atresia as fluid cannot drain posteriorly into the nasopharynx. There is deformity of both pinnae (Figure 3 and Figure 4).
Deformities of the semicircular canals (Figure 5).


Diagnosis: CHARGE syndrome

CHARGE is an acronym for the major clinical features of the syndrome (ocular Coloboma (75-90%), Heart defects (50-85%), Atresia of nasal choanae (35-65%), Retardation of growth/development, Genital anomalies (50-70% with male predominance), Ear anomalies (>90%). Additional associated features include facial dysmorphism, anosmia, auditory and vestibular anomalies, hypothalamo-hypophyseal dysfunction, and urinary tract anomalies. CHARGE syndrome occurs sporadically with an estimated prevalence of 1:10,000. Many patients with CHARGE syndrome have been genetically linked to mutations in the CHD7 gene, which encodes a protein within the chromodomain helicase DNA-binding (CHD) family of proteins responsible for gene expression regulation via chromatin remodeling. The ubiquitous expression of CHD7 protein helps explain the pleiotropic effects of patients with CHARGE syndrome.

Diagnosis of CHARGE syndrome initially required 4 of the cardinal 6 signs described by its acronym, with at least one sign being choanal atresia or coloboma. The diagnostic criteria were updated by Blake et al in 1998 to include brainstem anomalies, facial dysmorphism, and characteristic ear anomalies. More recently, and relying on the clinical triad of Coloboma-Choanal Atresia-semicircular Canal Anomalies, Verloes has proposed dividing the syndrome into typical, partial/incomplete, and atypical CHARGE syndromes based on 3 major signs (ocular coloboma, choanal atresia, hypoplastic semi-circular canals) and 5 minor signs (rhombencephalic dysfunction, hypothalamo-hypophyseal dysfunction, abnormal middle/external ear, mediastinal organ malformation, mental retardation).

Bilateral choanal atresia is usually osseous but may be membraneous and is usually detected in the newborn since neonates are obligate nose-breathers during feeding. Treatment is surgical with a transnasal or transpalatal approach to open the choanae. Ocular colobomas are often small and may only be detected via a funduscope. Vision is usually not impaired. Semicircular canal aplasia/dysplasia results in loss of nystagmus response to auditory caloric stimuli.