Macrocerebellum, epilepsy, intellectual disability, and gut malrotation in a child with a 16q24.1-q24.2 contiguous gene deletion

Abstract

Macrocerebellum is a rare condition characterized by enlargement of the cerebellum with conservation of the overall shape and cytoarchitecture. Here, we report on a child with a distinctive constellation of clinical features including macrocerebellum, epilepsy, apparent intellectual disability, dysautonomia, gut malrotation, and poor gut motility. Oligonucleotide chromosome microarray analysis identified a 16q24.1-q24.2 deletion that included four OMIM genes (FBXO31, MAP1LC3B, JPH3, and SLC7A5). Review of prior studies describing individuals with similar or overlapping16q24.1-q24.2 deletions identified no other reports of macrocerebellum. These observations highlight a potential genetic cause of this rare disorder and raise the possibility that one or more gene(s) in the 16q24.1-q24.2 interval regulate cerebellar development.

Keywords: FBXO31; JPH3; MAP1LC3B; SLC7A5; deletion syndrome; macrocerebellum.

Fig. 1

A: Sagittal T1 weighted midline image at the age of 2 months demonstrates increased cerebellar volume as evidenced by upward peak of the tentorium (white arrow). Increased volume of cerebellar vermis is also noted (black arrow). B: Normal age-matched control at 2 months. C: Off-midline image at the age of 3 years 7 months again demonstrates upward peaking of the tentorium (white arrow) along with relative increased amount of cerebellar grey matter in comparison to white matter volume (black arrows). D: Normal age matched control at 3 years 7 months.

Fig. 2

A schematic representation of the 16q24.1-q24.2 deletion in this clinical report and the RefSeq genes within the region. The asterisk denotes OMIM genes.