Congenital Glaucoma: a Novel Ocular Manifestation of Hajdu-Cheney Syndrome

Area of Science:

• Genetics
• Rare Diseases
• Ophthalmology

Background:

• Hajdu-Cheney Syndrome (HCS) is a rare multisystem disorder characterized by acro-osteolysis, severe osteoporosis, short stature, facial dysmorphism, neurological, cardiovascular, and renal abnormalities.
• HCS is typically caused by truncating mutations in NOTCH2 exon 34, leading to a stable, truncated NOTCH2 protein and enhanced Notch signaling.

Observation:

• This report details an infant with severe HCS manifestations, including congenital glaucoma as a significant, previously unreported early feature.
• The patient harbors a novel missense mutation in NOTCH2, distinct from previously identified truncating mutations.

Findings:

• The study identifies congenital glaucoma as a new ophthalmological manifestation of Hajdu-Cheney Syndrome.
• A novel, potentially pathogenic missense mutation in NOTCH2 is described, requiring further functional validation.
• This case expands the known phenotypic spectrum of HCS and its associated genetic underpinnings.

Implications:

• The findings suggest a potential role for Notch signaling in the development of the anterior chamber of the eye.
• This research may inform future diagnostic approaches and therapeutic strategies for HCS and related disorders.
• Understanding novel NOTCH2 mutations contributes to the broader knowledge of skeletal dysplasias and developmental abnormalities.