A boy with severe craniodiaphyseal dysplasia and apparently normal mother

Biegański, Tadeusz; Barańska, Dobromiła; Miastkowska, Irmina; Kobielski, Artur; Górska-Chrząstek, Magdalena; Kozlowski, K.

doi:10.1002/ajmg.a.31938

Cited by 11 publications

(7 citation statements)

References 10 publications

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“…Moreover, we demonstrated an amino acid change at the same location of the secretion signal of SOST gene in a previously published, unrelated CDD patient (Bieganski et al 2007). …”

Section: Introductionsupporting

confidence: 55%

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Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia

et al. 2011

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Sclerosteosis and Van Buchem disease are related recessive sclerosing bone dysplasias caused by alterations in the SOST gene. We tested the hypothesis that craniodiaphyseal dysplasia (CDD) (MIM 122860), an extremely rare sclerosing bone dysplasia resulting facial distortion referred to as ''leontiasis ossea'', could also be caused by SOST mutations. We discovered mutations c.61G[A (Val21Met) and c.61G[T (Val21Leu) two children with CDD. As these mutations are located in the secretion signal of the SOST gene, we tested their effect on secretion by transfecting the mutant constructs into 293E cells. Intriguingly, these mutations greatly reduced the secretion of SOST. We conclude that CDD, the most severe form of sclerotic bone disease, is part of a spectrum of disease caused by mutations in SOST. Unlike the other SOST-related conditions, sclerosteosis and Van Buchem disease that are inherited as recessive traits seem to be caused by a dominant negative mechanism.

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“…Moreover, we demonstrated an amino acid change at the same location of the secretion signal of SOST gene in a previously published, unrelated CDD patient (Bieganski et al 2007). …”

Section: Introductionsupporting

confidence: 55%

“…The patient was previously reported by Bieganski et al (2007). He presented with extensive osteosclerosis already evident at birth.…”

Section: Patientmentioning

confidence: 99%

Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia

et al. 2011

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Section: Glossarymentioning

confidence: 99%

“…CNS: Scant literature showing entrapment of cranial nerves secondary to progressive overgrowth of the craniofacial bones and tonsillar herniation with secondary syringomyelia in some patients. 240,241 Diaphyseal dysplasia, Camurati-Engelmann (OMIM: 131300) General information: Rare, autosomal dominant disorder of bone formation. 242 Somatic findings: Exophthalmos, limb pain, muscular weakness, waddling gait, and easy fatigability.…”

Section: Lenz-majewski Hyperostotic Dysplasia (Omim: 151050)mentioning

confidence: 99%

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

Wagner

Poretti

Benson

et al. 2016

Journal of Neuroimaging

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Genetic skeletal disorders (GSDs) are a heterogeneous group characterized by an intrinsic abnormality in growth and (re-)modeling of cartilage and bone. A large subgroup of GSDs has additional involvement of other structures/organs beside the skeleton, such as the central nervous system (CNS). CNS abnormalities have an important role in long-term prognosis of children with GSDs and should consequently not be missed. Sensitive and specific identification of CNS lesions while evaluating a child with a GSD requires a detailed knowledge of the possible associated CNS abnormalities. Here, we provide a pattern-recognition approach for neuroimaging findings in GSDs guided by the obvious skeletal manifestations of GSD. In particular, we summarize which CNS findings should be ruled out with each GSD. The diseases (n = 180) are classified based on the skeletal involvement (1. abnormal metaphysis or epiphysis, 2. abnormal size/number of bones, 3. abnormal shape of bones and joints, and 4. abnormal dynamic or structural changes). For each disease, skeletal involvement was defined in accordance with Online Mendelian Inheritance in Man. Morphological CNS involvement has been described based on extensive literature search. Selected examples will be shown based on prevalence of the diseases and significance of the CNS involvement. CNS involvement is common in GSDs. A wide spectrum of morphological abnormalities is associated with GSDs. Early diagnosis of CNS involvement is important in the management of children with GSDs. This pattern-recognition approach aims to assist and guide physicians in the diagnostic work-up of CNS involvement in children with GSDs and their management.

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“…Another very rare sclerotic bone disorder is craniodiaphyseal dysplasia (CDD), inherited in an autosomal dominant manner. Clinical manifestations include sclerosis and hyperostosis, especially of the skull and facial bones, resulting in facial dysmorphism or "leontiasis ossea" (49,58). Mutations causing CDD are located in the signal peptide of sclerostin and affect the secretion of sclerostin in a dominant negative manner.…”

Section: Wnt Inhibitorsmentioning

confidence: 99%

WNT Signaling and Bone: Lessons From Skeletal Dysplasias and Disorders

et al. 2020

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Skeletal dysplasias are a diverse group of heritable diseases affecting bone and cartilage growth. Throughout the years, the molecular defect underlying many of the diseases has been identified. These identifications led to novel insights in the mechanisms regulating bone and cartilage growth and homeostasis. One of the pathways that is clearly important during skeletal development and bone homeostasis is the Wingless and int-1 (WNT) signaling pathway. So far, three different WNT signaling pathways have been described, which are all activated by binding of the WNT ligands to the Frizzled (FZD) receptors. In this review, we discuss the skeletal disorders that are included in the latest nosology of skeletal disorders and that are caused by genetic defects involving the WNT signaling pathway. The number of skeletal disorders caused by defects in WNT signaling genes and the clinical phenotype associated with these disorders illustrate the importance of the WNT signaling pathway during skeletal development as well as later on in life to maintain bone mass. The knowledge gained through the identification of the genes underlying these monogenic conditions is used for the identification of novel therapeutic targets. For example, the genes underlying disorders with altered bone mass are all involved in the canonical WNT signaling pathway. Consequently, targeting this pathway is one of the major strategies to increase bone mass in patients with osteoporosis. In addition to increasing the insights in the pathways regulating skeletal development and bone homeostasis, knowledge of rare skeletal dysplasias can also be used to predict possible adverse effects of these novel drug targets. Therefore, this review gives an overview of the skeletal and extra-skeletal phenotype of the different skeletal disorders linked to the WNT signaling pathway.

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A boy with severe craniodiaphyseal dysplasia and apparently normal mother

Cited by 11 publications

References 10 publications

Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia

Identification of signal peptide domain SOST mutations in autosomal dominant craniodiaphyseal dysplasia

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

WNT Signaling and Bone: Lessons From Skeletal Dysplasias and Disorders

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