American Journal of Medical Genetics 43:823-828 (1992)
Chondrodysplasia Punctata: A Boy With X-Linked Recessive Chondrodysplasia Punctata Due t o an Inherited X-Y Translocation With a Current Classification of These Disorders Eric A. Wulfsberg, Jerri Curtis, and Carol H. Jayne Medical GeneticslDysmorphology, National Naval Medical Center, Uniformed Services University of the Health Sciences (E.A.W); Neonatology, Uniformed Services University of the Health Sciences (J.C.), Bethesda, Maryland; and Nichols Institute, S a n Juan Capistrano, California (C.H.J.) INTRODUCTION Chondrodysplasia punctata (CDP) is the name applied to a heterogeneous group of rare bone dysplasias characterized by punctate calcifications of cartilage. The punctate calcifications are nonspecific and have been seen in a wide variety of disorders including the Zellweger syndrome [Zellweger, 19871,warfarin [Shaul et al., 19751,dilantin [Hanson and Smithy, 19751,alcohol [Badosis et al., 19831 and rubella embryopathy [Pike et al., 19901,vitamin-K-epoxide-reductase deficiency [Pauli et al., 19871,chromosome trisomies 18 and 21 [Le Marec et al., 19761,the Smith-Lemli-Opitz syndrome [Gibson, 19651,prenatal infectious chondritis [Walker, 19821, autosomal dominant multiple epiphyseal dysplasia [Silverman, 19691, acrodysostosis [Viljoen and Beighton, 19911,hypothyroidism [Borget al., 19751,and other rare disorders [Taybi and Lachman, 19901.CDP was first described by Conradi 119141 and his name or the eponym Conradi-Hunermann is frequently and indiscriminately applied to this group of dysplasias. At present, 3 single gene types of CDP have been defined. These include an autosomal recessive rhizomelic type (RCDP) due to a peroxisomal enzyme defect [Heyman et al., 19851,an X-linked dominant type with presumed male lethality (XDCDP) [Happle, 19791,and an X-linked recessive type (XRCDP)that has only been described as part of contiguous gene deletion syndromes [Curry et al., 1984;Ballabio et al., 19891.We report on a 0 1992 Wiley-Liss, Inc. male infant with short stature, nasal hypoplasia, hypoplastic distal phalanges, chondrodysplasia punctata, KEY WORDS ichthyosis, steroid sulfatase ichthyosis, hypoplastic genitalia, and a 46, deficiency, Kallmann syn-X, + der(X),t(X;Y)(p22.32;ql1.21),Y karyotype. This drome, mental retardation patient’s phenotype, karyotype, and genomic DNA probe analysis are consistent with a contiguous Xp gene deletion syndrome including (1)the XRCDP gene, ( 2 )a nonspecific X-linked mental retardation gene, (3) the Received for publication May 6,1991; revision received NovemX-linked steroid sulfatase gene (STS), and (4) the ber 6, 1991. Address reprint requests: to Eric A. Wulfsberg, M.D., Division of X-linked Kallmann syndrome (XLK) gene. We review Human Genetics, University of Maryland School of Medicine, 405 similar cases and discuss a current classification of chondrodysplasia punctata. W. Redwood St., Suite 400, Baltimore, MD 21021-1703. Chondrodysplasia punctata (CDP) is a heterogeneous group of rare bone dysplasias characterized by punctate calcification of cartilage. The punctate calcificationsare nonspecific and have been seen in a wide variety of disorders including the Zellweger syndrome, warfarin, dilantin, alcohol and rubella embryopathies, vitamin-H-epoxide-reductase deficiency, chromosome trisomies 18 and 21, the Smith-Lemli-Opitz syndrome, prenatal infectious chondritis, hypothyroidism, and other rare disorders. We report on a boy with short stature, developmental delay, nasal hypoplasia, telebrachydactyly, hypoplastic genitalia, CDP, ichthyosis, hypoplastic genitalia, and a 46 - X, + der(X),t(X;Y)(p22.31; q11.21), Y karyotype. Genomic DNA probe analysis was interpreted as showing that the translocation breakpoint was within the X-linkedKallmann syndrome gene. We review a current classificationof these disorders that includes 3 well-defined single gene disorders. These include an autosomal recessive rhizomelic type with early lethality, an X-linked dominant type with presumed male lethality, and an X-linked recessive type that has only been described as part of a contiguous gene deletion syndrome.
0 1992 Wiley-Liss, Inc.
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respiratory distress due to worsening of the right hydronephrosis and hydroureter requiring right nephrectomy and ureterectomy. Pathologic examination documented multicystic renal dysplasia that was interpreted as due to hydronephrosis. At age 4 weeks the patient developed generalized ichthyosis (Fig. 2). Thyroid and adrenal function were normal. Testosterone was 18 ng/dl (normal 1-177 ng/dl), luteinizing hormone (LH) was 0.2 mIU/ml (normal
Chondrodysplasia Punctata: A Boy With X-Linked Recessive Chondrodysplasia Punctata Due t o an Inherited X-Y Translocation With a Current Classification of These Disorders Eric A. Wulfsberg, Jerri Curtis, and Carol H. Jayne Medical GeneticslDysmorphology, National Naval Medical Center, Uniformed Services University of the Health Sciences (E.A.W); Neonatology, Uniformed Services University of the Health Sciences (J.C.), Bethesda, Maryland; and Nichols Institute, S a n Juan Capistrano, California (C.H.J.) INTRODUCTION Chondrodysplasia punctata (CDP) is the name applied to a heterogeneous group of rare bone dysplasias characterized by punctate calcifications of cartilage. The punctate calcifications are nonspecific and have been seen in a wide variety of disorders including the Zellweger syndrome [Zellweger, 19871,warfarin [Shaul et al., 19751,dilantin [Hanson and Smithy, 19751,alcohol [Badosis et al., 19831 and rubella embryopathy [Pike et al., 19901,vitamin-K-epoxide-reductase deficiency [Pauli et al., 19871,chromosome trisomies 18 and 21 [Le Marec et al., 19761,the Smith-Lemli-Opitz syndrome [Gibson, 19651,prenatal infectious chondritis [Walker, 19821, autosomal dominant multiple epiphyseal dysplasia [Silverman, 19691, acrodysostosis [Viljoen and Beighton, 19911,hypothyroidism [Borget al., 19751,and other rare disorders [Taybi and Lachman, 19901.CDP was first described by Conradi 119141 and his name or the eponym Conradi-Hunermann is frequently and indiscriminately applied to this group of dysplasias. At present, 3 single gene types of CDP have been defined. These include an autosomal recessive rhizomelic type (RCDP) due to a peroxisomal enzyme defect [Heyman et al., 19851,an X-linked dominant type with presumed male lethality (XDCDP) [Happle, 19791,and an X-linked recessive type (XRCDP)that has only been described as part of contiguous gene deletion syndromes [Curry et al., 1984;Ballabio et al., 19891.We report on a 0 1992 Wiley-Liss, Inc. male infant with short stature, nasal hypoplasia, hypoplastic distal phalanges, chondrodysplasia punctata, KEY WORDS ichthyosis, steroid sulfatase ichthyosis, hypoplastic genitalia, and a 46, deficiency, Kallmann syn-X, + der(X),t(X;Y)(p22.32;ql1.21),Y karyotype. This drome, mental retardation patient’s phenotype, karyotype, and genomic DNA probe analysis are consistent with a contiguous Xp gene deletion syndrome including (1)the XRCDP gene, ( 2 )a nonspecific X-linked mental retardation gene, (3) the Received for publication May 6,1991; revision received NovemX-linked steroid sulfatase gene (STS), and (4) the ber 6, 1991. Address reprint requests: to Eric A. Wulfsberg, M.D., Division of X-linked Kallmann syndrome (XLK) gene. We review Human Genetics, University of Maryland School of Medicine, 405 similar cases and discuss a current classification of chondrodysplasia punctata. W. Redwood St., Suite 400, Baltimore, MD 21021-1703. Chondrodysplasia punctata (CDP) is a heterogeneous group of rare bone dysplasias characterized by punctate calcification of cartilage. The punctate calcificationsare nonspecific and have been seen in a wide variety of disorders including the Zellweger syndrome, warfarin, dilantin, alcohol and rubella embryopathies, vitamin-H-epoxide-reductase deficiency, chromosome trisomies 18 and 21, the Smith-Lemli-Opitz syndrome, prenatal infectious chondritis, hypothyroidism, and other rare disorders. We report on a boy with short stature, developmental delay, nasal hypoplasia, telebrachydactyly, hypoplastic genitalia, CDP, ichthyosis, hypoplastic genitalia, and a 46 - X, + der(X),t(X;Y)(p22.31; q11.21), Y karyotype. Genomic DNA probe analysis was interpreted as showing that the translocation breakpoint was within the X-linkedKallmann syndrome gene. We review a current classificationof these disorders that includes 3 well-defined single gene disorders. These include an autosomal recessive rhizomelic type with early lethality, an X-linked dominant type with presumed male lethality, and an X-linked recessive type that has only been described as part of a contiguous gene deletion syndrome.
0 1992 Wiley-Liss, Inc.
824
Wulfsberg et al.
respiratory distress due to worsening of the right hydronephrosis and hydroureter requiring right nephrectomy and ureterectomy. Pathologic examination documented multicystic renal dysplasia that was interpreted as due to hydronephrosis. At age 4 weeks the patient developed generalized ichthyosis (Fig. 2). Thyroid and adrenal function were normal. Testosterone was 18 ng/dl (normal 1-177 ng/dl), luteinizing hormone (LH) was 0.2 mIU/ml (normal
