A Novel YY1AP1 Variant in Grange Syndrome: Clinical and Molecular Findings in Eight Individuals With a Dual Molecular Diagnosis Involving CLMP in One Patient.
Akçahan Akalın, Veysel Öz, Ayşe Seda Pınarbaşı et al.
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Case in brief
This report describes eight individuals from a consanguineous family diagnosed with Grange syndrome, characterized by multiple fractures, bone fragility, and other systemic manifestations. A novel biallelic variant in YY1AP1 was identified in all affected individuals. Notably, one patient also had a dual diagnosis with a pathogenic variant in CLMP. Treatment with bisphosphonates improved bone mineral density in some patients.
What made this case unusual
The presence of a dual molecular diagnosis involving both YY1AP1 and CLMP in one patient is noteworthy, highlighting the complexity of genetic contributions to the clinical phenotype.
Diagnostic / clinical pearl
Clinicians should consider Grange syndrome in patients presenting with multiple fractures and systemic symptoms, particularly in consanguineous families, and investigate for potential dual diagnoses.
Why it matters
This case underscores the importance of comprehensive genetic testing in rare syndromes, as it can reveal additional pathogenic variants that may influence management and prognosis.