Coronal Clival Cleft in CHARGE Syndrome: Fetal MRI Series

BACKGROUND AND PURPOSE: CHARGE is a syndrome that affects the brain, eyes, ears, heart, face, and genitourinary system. Prenatal diagnosis could optimize counseling, delivery planning, and therapeutic interventions; however, reports of associated fetal neuroimaging features are scarce. While some findings are nonspecific, olfactory, inner ear, and skull base anomalies are commonly present and may be observable at the time of fetal imaging. We sought to determine the scope of prenatal CNS MRI findings in CHARGE syndrome with emphasis on findings not included in the diagnostic criteria for CHARGE syndrome, such as coronal clival cleft.

MATERIALS AND METHODS: Retrospective review of fetal +/− postnatal neuroimaging from patients with genetic diagnosis of CHARGE syndrome was conducted. Brain, ear, eye, face, and skull base bone abnormalities were documented. Descriptive statistics were employed to characterize the findings.

RESULTS: Eighteen fetal-maternal dyads were included. Median gestational age at time of prenatal MRI was 26.25 weeks. Thirteen (72%) subjects were born alive, of which 10 (55.6%) were males. One died on the first day of life (5.6%) and 4/18 (22.2%) underwent termination of pregnancy. Twelve (66.7%) had postnatal brain MRI and/or temporal bone CT. On prenatal MRI, coronal clival cleft was seen in 72% of the cases and confirmed in all patients with postnatal imaging. Inner ear dysplasia was universally seen in all prenatal MRI, except for 1 case, in which this was not evaluable, and confirmed in all cases postnatally. On prenatal imaging, olfactory apparatus hypoplasia/absence was detected in 83% of the cases, followed by globe dysmorphia and/or colobomas in 44% of the cases, atresia of choanae (39%), facial clefts (22%), and cerebellar malformation (16.7%). Of the 10 cases with postnatal brain MRI available, 4 (40%) demonstrated cerebellar gray matter heterotopia.

CONCLUSIONS: The most common fetal neuroimaging findings supporting the diagnosis of CHARGE syndrome are olfactory deficiency and inner ear dysplasia. Coronal clival clefts are often present and are frequently visible on prenatal MR imaging. The presence of a clival coronal cleft should raise the possibility of CHARGE syndrome, particularly when associated with other known cardinal findings, such as cerebellar dysgenesis, olfactory apparatus deficiency, and inner ear dysplasia.