Acrocallosal syndrome in fetus: focus on additional brain abnormalities

Area of Science:

• Genetics and Developmental Biology
• Neuropathology
• Medical Genetics

Background:

• Acrocallosal syndrome (ACS) is a rare autosomal recessive disorder.
• It presents with craniofacial dysmorphism, corpus callosum abnormalities, and limb malformations.
• Severe intellectual disability is a hallmark of ACS.

Observation:

• This study reports two fetal cases of acrocallosal syndrome with detailed neuropathological examination.
• Case 1: A 25-week male fetus with craniofacial and limb anomalies, including syndactyly and preaxial polydactyly.
• Case 2: A 33-week male fetus with hand and limb anomalies, including syndactyly and a broad thumb.

Findings:

• Both fetuses exhibited agenesis of the corpus callosum and interhemispheric cysts.
• Microscopic analysis revealed dysplastic cortical areas with neuronal clusters in the white matter.
• Additional findings included hypoplastic pons and cerebellum, dysplastic olivary nuclei, and neuronal heterotopias.

Implications:

• These findings provide new insights into the spectrum of brain abnormalities in acrocallosal syndrome.
• The detailed neuropathological data may improve ante- and post-natal diagnosis of ACS.
• This research could facilitate comparisons with animal models and gene identification efforts for ACS.