Complex craniosynostosis is associated with the 2p15p16.1 microdeletion syndrome

Area of Science:

• Genetics
• Human Genetics
• Medical Genetics

Background:

• Craniosynostosis is a condition characterized by the premature fusion of skull bones.
• Microcephaly is a congenital condition where the head is significantly smaller than average.
• The 2p15p16.1 microdeletion syndrome is a recently identified genetic disorder associated with intellectual disability and microcephaly.

Purpose of the Study:

• To identify genetic causes of craniosynostosis in patients.
• To further characterize the 2p15p16.1 microdeletion syndrome.
• To expand the understanding of the clinical spectrum associated with 2p15p16.1 deletions.

Main Methods:

• Genomic screening using Affymetrix 250K SNP arrays.
• Fluorescence in situ hybridization (FISH) analysis for deletion confirmation.
• Quantitative Polymerase Chain Reaction (qPCR) for precise deletion size and copy number determination.

Main Results:

• Two patients with craniosynostosis and microcephaly were identified with overlapping deletions in the 2p15p16.1 region.
• The deletions were approximately 6.8 and 6.9 Mb in size, confirmed by FISH and qPCR.
• Analysis of nine reported patients, including these two, shows that microcephaly (8/9) and intellectual disability (9/9) are consistent features.

Conclusions:

• The 2p15p16.1 microdeletion is associated with craniosynostosis, microcephaly, and intellectual disability.
• This study adds craniosynostosis to the phenotypic spectrum of the 2p15p16.1 microdeletion syndrome.
• Further characterization of this microdeletion syndrome is crucial for understanding its clinical variability.