Prenatal diagnosis of Chudley-McCullough syndrome

Abstract

Chudley-McCullough syndrome (CMS) is an autosomal-recessive disorder characterized by a complex brain malformation and profound congenital sensorineural hearing loss. Postnatal brain imaging findings include ventriculomegaly, partial agenesis of corpus callosum, inferior cerebellar dysplasia, arachnoid cysts, and malformations of cortical development including frontal subcortical heterotopia and polymicrogyria. Prenatal diagnosis of CMS is important due to the markedly less severe neurodevelopmental prognosis compared to disorders with similar brain imaging findings. We report prenatal imaging features that help distinguish CMS from other disorders, including slit-like frontal horns, agenesis of the corpus callosum, frontal subcortical heterotopia, arachnoid cysts, and cerebellar dysplasia. © 2016 Wiley Periodicals, Inc.

Keywords: Chudley-McCullough syndrome; agenesis of corpus callosum; fetal MR; polymicrogyria; prenatal diagnosis; ventriculomegaly.

FIG. 1.

Third-trimester prenatal imaging shows findings consistent with Chudley–McCullough syndrome. (A) Single oblique-axial image of fetal head acquired during ultrasound performed at 28 + 1 weeks shows lateral ventriculomegaly and captures abnormally pointed morphology of lateral ventricle frontal horn (arrow), appreciated only in retrospect. Fetal brain MR single-shot fast-spin echo T2-weighted images were later acquired at 33 + 3 weeks; (B) Axial image through the lateral ventricle atria shows abnormal enlargement of the lateral ventricles (LV). Note parallel orientation of the lateral ventricles in axial plane (A and B), typical of dysgenesis of the corpus callosum; (C and D) Axial images through the frontal horns show pointed, small frontal horns of the lateral ventricles and abnormal hypointense signal matching that of gray-matter in the subcortical tissue medially (arrows), consistent with heterotopia; (E) Axial image through the inferior cerebellum shows abnormal organization of the cerebellar folia and fissures (arrows), suggestive of cerebellar dysplasia.

FIG. 2.

Postnatal brain MR imaging performed at 6 days of life shows findings consistent with Chudley–McCullough syndrome. (A) Axial T2-weighted image through the lower cerebral hemispheres shows disproportionate enlargement of the lateral ventricle (LV) atria (black arrowheads indicate choroid); (B) Axial and (C) coronal T2-weighted images through the bifrontal lobes show abnormal, serpiginous signal (white arrows in B,C) in the subcortical white matter, consistent with gray-matter heterotopia, and abnormal gyriform pattern medially (white arrowheads), consistent with polymicrogyria; (D) Axial T2-weighted image through the inferior cerebellar hemispheres shows an abnormally lobulated morphology of the cerebellum bilaterally (white arrows in D), with a disorganized folia pattern, indicating dysplasia. Inferior vermian dysplasia was also observed (not shown).

FIG. 3.

Brain MRI findings of Chudley–McCullough in two siblings. (A and B) Axial T2-weighted images through the lateral ventricles (LV) of the older sister at age 3 years shows ventriculomegaly and an abnormal left parasagittal cyst (*). Bifrontal subcortical heterotopia is thicker than seen in her newborn sister; (C) Sagittal T1-weighted image of the same older sister also shows the absence of the posterior corpus callosum (white arrow) and the mass effect upon the cerebellar vermis (arrowhead) by the near-midline cyst (*); (D) Axial T2-weighted image through the frontal lobes of the older brother, imaged at age 1 month, shows the same colpocephalic configuration of the lateral ventricles (LV) and slit-like frontal horns. Bifrontal heterotopia (arrows in D) and polymicrogyria (arrowhead in D) are readily apparent; (E) Sagittal T1-weighted image through the midline shows the same features as in the older sister, with frontal polymicrogyria (black arrowheads), partial agenesis of the corpus callosum (white arrow), and quadrigeminal plate cyst (*).