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Phenotypically dissimilar hypophosphatasia in two sibships
J D Macfarlane1, H M Kroon, J J van der Harten
1Department of Rheumatology, University Hospital, Leiden, The Netherlands.
American Journal of Medical Genetics
|January 1, 1992
Summary
Hypophosphatasia typically follows family patterns, but two kindreds showed siblings with vastly different disease severity. This suggests autosomal recessive inheritance may explain varied clinical presentations in hypophosphatasia.
Area of Science:
- Genetics
- Pediatrics
- Metabolic Disorders
Background:
- Hypophosphatasia is a rare inherited metabolic bone disease caused by mutations in the ALPL gene, leading to impaired bone mineralization.
- Both autosomal dominant and autosomal recessive forms have been documented, with generally consistent clinical phenotypes within families.
Observation:
- Two kindreds with hypophosphatasia presented unusual intrafamilial variability in disease severity among siblings.
- One sibling pair exhibited the severe perinatal and infantile forms, while the other pair displayed milder dental and adult forms.
Findings:
- Despite the marked differences in clinical presentation, both families showed evidence of consanguinity.
- The pattern of varied clinical expression in affected siblings supports an autosomal recessive mode of inheritance for hypophosphatasia in these cases.
Implications:
- This intrafamilial variability challenges the typical understanding of hypophosphatasia inheritance patterns.
- Further research into genetic modifiers or epigenetic factors may be warranted to explain the broad spectrum of clinical outcomes in autosomal recessive hypophosphatasia.