Association of Meier-Gorlin and microcephalic osteodysplastic primordial dwarfism type II clinical features in an...

Area of Science:

• Genetics
• Developmental Biology
• Clinical Medicine

Background:

• Autosomal recessive primary microcephaly type 3 (MCPH3) is a rare genetic disorder.
• It is characterized by severe microcephaly, neurodevelopmental delay, sensorineural hearing loss, skin pigmentation abnormalities, and ocular defects.
• MCPH3 is caused by pathogenic variants in the CDK5RAP2 gene, which plays a role in centrosome function.

Observation:

• This study describes a 10-year-old girl with a biallelic exonic frameshift variant in CDK5RAP2.
• The patient exhibited previously unreported features, including skeletal abnormalities typically associated with Meier-Gorlin syndrome and microcephalic osteodysplastic primordial dwarfism type II (MOPDII).

Findings:

• The findings expand the known clinical phenotype of MCPH3.
• This case highlights that MCPH3 can present with skeletal dysplasia, mimicking other primordial dwarfism syndromes.
• The study emphasizes the centrosomal basis of this form of primary microcephaly.

Implications:

• The study underscores the importance of comprehensive skeletal defect screening in individuals diagnosed with MCPH3.
• Recognizing this expanded phenotype can lead to earlier and more accurate diagnosis.
• Further research into CDK5RAP2 function may reveal new therapeutic targets for microcephaly and related disorders.