Infantile systemic hyalinosis: Variable grades of severity

Area of Science:

• Genetics
• Pediatrics
• Rare Diseases

Background:

• Infantile systemic hyalinosis (ISH) is an autosomal recessive disorder.
• Classical ISH presents with hypotonia, contractures, skin lesions, osteopenia, and growth deficiency.

Purpose of the Study:

• To investigate genetic mutations in ISH.
• To characterize the phenotypic spectrum of ISH in affected families.

Main Methods:

• Genotypic confirmation of ISH in two severe cases.
• Phenotypic assessment of siblings and cousins for disease inheritance.
• Whole exome sequencing to identify genetic variants.

Main Results:

• Two severe ISH cases exhibited craniosynostosis, contractures, and joint dislocations.
• Identified a novel heterozygous non-synonymous substitution (c.58T>A) in the ANTRX2 gene.
• Three relatives showed asymptomatic skin and skeletal abnormalities, including hypoplastic clavicles and coxa vara.

Conclusions:

• Extensive family screening is crucial in consanguineous families with ISH.
• Identified novel ANTRX2 mutations and expanded the phenotypic characterization of ISH.
• Observed previously undescribed asymptomatic skin and skeletal findings in mild/moderate ISH types.