American Journal of Medical Genetics 3 6 15-22 (1990)
Infantile Hypophosphatasia: Autosomal Recessive Transmission to Two Related Sibships Cynthia A. Moore, Jewel1 C. Ward, Marian L. Rivas, H. Lynn Magill, and Michael P. Whyte Division of Genetics, The Boling Center for Developmental Disabilities, Department of Pediatrics ( C A.M., J.C. W., M.L.R.), and Radiology (H.L.M.) LeBonheur Children$ Medical Center, University of Tennessee Center for the Health Sciences, Memphis; Division of Bone and Mineral Diseases, Departments of Medicine and Pediatrics, Washington University School of Medicine, St. Louis ( M P .W.) Hypophosphatasia, a rare heritable form of rickets/osteomalacia,is characterized by deficient activity of the tissue nonspecific (liver/ bonelkidney) isoenzyme of alkaline phosphatase (ALP). Signs may be present prenatally or not until late adult life. Although the infantile form of hypophosphatasia has usually been categorized as an autosomal recessive (AR) disorder, several studies suggest that childhood cases are the consequenceof either AR or autosomal dominant (AD) inheritance and adult cases are primarily AD. Eastman and Bixler (J Craniofac Genet Dev Biol 3:213-234, 1983) propose that all cases of hypophosphatasia may reflect AD inheritance with 85% penetrance and homozygous lethality. We report on 3 patients with hypophosphatasia in a black family, first manifested clinically during infancy, where the pattern of inheritance for each is consistent with AR transmission. Two were brothers who died from the disorder. The other patient, a cousin, presented with classic stigmata of hypophosphatasia during infancy, but is now age 5% years and has had a much milder clinical course. Although consanguinityis absent, the maternal grandmothers are sibs as are the maternal grandfathers and the paternal grandmothers. The family history is otherwise negative for skeletal or dental disease. Laboratory and radiographic results are conReceived for publication June 23,1988; revision received November 27, 1989. Address reprint requests to Jewel1 C. Ward, M.D., Ph.D., The Boling Center for Developmental Disabilities, 711 Jefferson, Room 522, Memphis, TN 38105. Cynthia A. Moore’s current address is Department of Medical Genetics, Indiana University School of Medicine, 975 West Walnut Street, Indianapolis, IN 46202. Presented in part at the 35th Annual Meeting of The American Society of Human Genetics, The American. Journal of Human Genetics 36:66-S, 1984.
0 1990 Wiley-Liss, Inc.
sistent with heterozygosity in each parent. Fibroblast ALP activity is
Infantile Hypophosphatasia: Autosomal Recessive Transmission to Two Related Sibships Cynthia A. Moore, Jewel1 C. Ward, Marian L. Rivas, H. Lynn Magill, and Michael P. Whyte Division of Genetics, The Boling Center for Developmental Disabilities, Department of Pediatrics ( C A.M., J.C. W., M.L.R.), and Radiology (H.L.M.) LeBonheur Children$ Medical Center, University of Tennessee Center for the Health Sciences, Memphis; Division of Bone and Mineral Diseases, Departments of Medicine and Pediatrics, Washington University School of Medicine, St. Louis ( M P .W.) Hypophosphatasia, a rare heritable form of rickets/osteomalacia,is characterized by deficient activity of the tissue nonspecific (liver/ bonelkidney) isoenzyme of alkaline phosphatase (ALP). Signs may be present prenatally or not until late adult life. Although the infantile form of hypophosphatasia has usually been categorized as an autosomal recessive (AR) disorder, several studies suggest that childhood cases are the consequenceof either AR or autosomal dominant (AD) inheritance and adult cases are primarily AD. Eastman and Bixler (J Craniofac Genet Dev Biol 3:213-234, 1983) propose that all cases of hypophosphatasia may reflect AD inheritance with 85% penetrance and homozygous lethality. We report on 3 patients with hypophosphatasia in a black family, first manifested clinically during infancy, where the pattern of inheritance for each is consistent with AR transmission. Two were brothers who died from the disorder. The other patient, a cousin, presented with classic stigmata of hypophosphatasia during infancy, but is now age 5% years and has had a much milder clinical course. Although consanguinityis absent, the maternal grandmothers are sibs as are the maternal grandfathers and the paternal grandmothers. The family history is otherwise negative for skeletal or dental disease. Laboratory and radiographic results are conReceived for publication June 23,1988; revision received November 27, 1989. Address reprint requests to Jewel1 C. Ward, M.D., Ph.D., The Boling Center for Developmental Disabilities, 711 Jefferson, Room 522, Memphis, TN 38105. Cynthia A. Moore’s current address is Department of Medical Genetics, Indiana University School of Medicine, 975 West Walnut Street, Indianapolis, IN 46202. Presented in part at the 35th Annual Meeting of The American Society of Human Genetics, The American. Journal of Human Genetics 36:66-S, 1984.
0 1990 Wiley-Liss, Inc.
sistent with heterozygosity in each parent. Fibroblast ALP activity is
