Teaching Case

A preterm (36 weeks) newborn female presented with complaints of seizures on day 14th of life. On examination, there was the presence of dysmorphic facies, cleft lip and palate, polydactyly and disc coloboma. Echocardiography revealed moderate patent ductus arteriosus with moderate pulmonary hypertension.

MRI brain revealed vermian hypoplasia and small pons with enlarged cisterna magna and dilated 4th ventricle with posterior angulation of ossification centre of basi-occiput (Figure 1a). A note was made of left optic coloboma (Figure 2a) with bilateral cleft lip and palate with premaxillary protrusion (Figure 2b). Dedicated MRI temporal bone (Figures 3a, 3b and 3c) for inner ear structures revealed bilateral vestibular and posterior SCC dysplasia with lateral/superior SCC aplasia.

There was hypoplasia of the apical turn of the cochlea on both sides. Bilateral IAC and cochlear aperture were narrowed with hypoplastic facial canals. Two nerves were seen in bilateral CP angle cisterns with the hypoplastic left facial nerve. However, bilateral VII-VIII nerve complexes in IAC could not be differentiated separately. Bilateral olfactory tract/sulcus aplasia is noted (Figure 4).

Background

CHARGE syndrome is a rare congenital disorder with autosomal dominant inheritance and an incidence of 1 in 10,000 births, approximately [1]. Though the features were first identified by Hall and Hittner, the acronym CHARGE syndrome was coined by Pagon, who described the cardinal anomalies such as coloboma, choanal atresia, heart defects, genital abnormalities, retarded growth, and ear malformation [2]. The disease is sporadic [3] in nature and is caused by mutations in the CDH7 gene, located on chromosome 8 (8q12) [1].

Clinical perspective

Initial presentation in the prenatal stage with IUGR, detection of cleft lip/palate, and congenital heart disease should raise suspicion. Neonates usually present with coloboma [4], inability to pass nasogastric tube due to choanal atresia, dysmorphic features, respiratory distress and hearing loss [1]. Clinical criteria modified by Verloes emphasise the “3C” – Coloboma, Choanal atresia, and Canals (hypoplastic semicircular). Among these, hypoplasia of semicircular canals is the most constantly present anomaly [3]. Rhombencephalic dysfunction, hypothalamo-hypophyseal dysfunction, external/middle ear malformation, mediastinal viscera malformation, and mental retardation are included in minor criteria [3].

Imaging perspective

Imaging studies identify multiple anomalies involving ear, orbit, nasal cavity, and brain [3]. CHARGE syndrome is initially diagnosed based on clinical findings, which generally detect coloboma and choanal atresia, and temporal bone imaging to look for middle and inner ear defects [5]. MR imaging surpasses CT in the preoperative evaluation of these patients as it can better delineate cochlear nerve aplasia and also detect brain abnormalities that can modify the treatment plan when brain stem or cochlear implantation is required [3].

MRI imaging findings include semicircular canal (SCC) dysplasia, cochlear dysplasia, vestibular dysplasia, absence of the cochlear aperture, cochlear nerve deficiency, internal auditory canal (IAC) dysplasia, and an enlarged vestibular aqueduct.

MRI can also detect the structural abnormalities of the head, including cleft lip/palate, coloboma, olfactory hypoplasia and brain anomalies, like brainstem hypoplasia, vermian hypoplasia, and ventriculomegaly [3].

Superior rotation of the vermis, increased tegmento-vermian angle (18° to 45°) (Figure 1b), and variable cerebellar hypoplasia, i.e., diminished vermian volume below the fastigium-declive line are findings suggestive of vermian hypoplasia [6].

Outcome

Multidisciplinary management is required for management of neonates with CHARGE syndrome.

Take home message / teaching points

As CHARGE syndrome exhibits phenotypic heterogeneity with several overlapping features with other syndromes, detection of semicircular canals aplasia/dysplasia, brainstem hypoplasia, olfactory hypoplasia and basiocciput abnormalities on CT and MRI help in prompt recognition and differentiation from other syndromes.