Osteopathia striata with cranial sclerosis: highly variable phenotypic expression within a family

Area of Science:

• Genetics
• Medical Genetics
• Rare Diseases

Background:

• Osteopathia striata with cranial sclerosis (OS-CS) is an autosomal dominant condition.
• Understanding the full spectrum of OS-CS manifestations is crucial for diagnosis and management.

Observation:

• A four-generation family with five affected individuals exhibiting OS-CS was studied.
• The proband presented with an unusually severe form of OS-CS, displaying nearly all known syndrome associations.
• Two previously undescribed manifestations were noted: proximal osteolysis of the fibula and congenital urological abnormalities in the proband, and holoprosencephaly sequence in her sister.

Findings:

• The study demonstrates the wide spectrum of gene expression in autosomal dominant OS-CS.
• Severe OS-CS can present with a comprehensive set of known clinical features.
• New phenotypic associations, including fibular osteolysis, urological abnormalities, and holoprosencephaly, expand the known clinical spectrum of OS-CS.

Implications:

• These findings broaden the understanding of OS-CS, suggesting a more extensive range of potential clinical presentations.
• Recognition of these novel associations may improve diagnostic accuracy and genetic counseling for families affected by OS-CS.
• Further research into the genetic underpinnings of OS-CS is warranted to explain the observed variability and novel findings.