The hidden brain in cleft: Clinical presentation in patients with median cerebrofacial dysgenesis

Median cerebrofacial dysgenesis (MCFD) is a rare subset of median cerebrofacial malformations, characterized by cleft, hypoplasia/agenesis of midline facial structures in association with brain anomalies. It remains underrecognized and poorly characterized. This study defines craniofacial and neuroimaging features and evaluates the correlations in MCFD.

A retrospective review was conducted on 33 patients with MCFD at Chang Gung Memorial Hospital. Inclusion criteria were cleft lip/palate and median craniofacial anomalies with available brain scans. Craniofacial morphology, neuroimaging findings, and survival were analyzed.

There were 13 males and 20 females. Nineteen had bilateral and 14 had unilateral clefts. They exhibited microcephaly with their head circumference less than 3rd percentile for age and gender. Common brain anomalies included hypoplastic to absent septum pellucidum/corpus callosum, frontal lobe fusion, thalamic/basal ganglia fusion, and ventriculomegaly. Craniofacial findings included absent to hypoplastic prolabium/premaxilla, absent upper labial frenulum, nasal hypoplasia, and hypotelorism. Twelve patients survived with severe psychomotor delay and 21 died with a mean lifespan of 9.2 months. Greater forebrain fusion was significantly associated with lower survival. In contrast, there was no significant difference in survival between patients with absent and those with hypoplastic prolabium/premaxilla. No correlation was found between craniofacial severity and brain anomalies.

MCFD represents a distinct clinical and radiological entity in patients with clefts. Neuroimaging plays a pivotal role in diagnosis, prognosis, and treatment planning. Reduced head circumference serves as an early indicator of underlying cerebral malformations. Optimal management of these patients requires multidisciplinary evaluation and individualized consideration.