Craniometaphyseal dysplasia: a case report and review of medical and surgical management

Sheppard, William M.; Shprintzen, Robert J.; Tatum, Sherard A.; Woods, Charles I.

doi:10.1016/s0165-5876(03)00133-2

Cited by 16 publications

(3 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CMD patients present with elevated serum ALP, increased TRACP, and normal to slightly/transiently elevated PTH levels (3,6,13,30) . In sera of 10‐wk‐old fasted Ank KI/KI mice, we detected increases in ALP, a nonspecific bone marker, and TRACP5b, a marker of osteoclast numbers (Table 3).…”

Section: Resultsmentioning

confidence: 78%

Introduction of a Phe377del Mutation in ANK Creates a Mouse Model for Craniometaphyseal Dysplasia

Chen

Wang

Strecker

et al. 2009

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Craniometaphyseal dysplasia (CMD) is a monogenic human disorder characterized by thickening of craniofacial bones and flaring metaphyses of long bones. Mutations for autosomal dominant CMD have been identified in the progressive ankylosis gene ANKH. Previous studies of Ank loss-of-function models, Ank null/null and Ank ank/ank mice, suggest that Ank plays a role in the regulation of bone mineralization. However, the mechanism for Ank mutations leading to CMD remains unknown. We generated the first knockin (KI) mouse model for CMD expressing a human mutation (Phe377 deletion) in ANK. Homozygous Ank knockin mice (Ank KI/KI ) replicate many typical features of human CMD including hyperostosis of craniofacial bones, massive jawbones, decreased diameters of cranial foramina, obliteration of nasal sinuses, fusion of middle ear bones, and club-shaped femurs. In addition, Ank KI/KI mice have increased serum alkaline phosphatase and TRACP5b, as reported in CMD patients. Biochemical markers of bone formation and bone resorption, N-terminal propeptide of type I procollagen and type I collagen cross-linked C-terminal telopeptide, are significantly increased in Ank KI/KI mice, suggesting increased bone turnover. Interestingly, Ank KI/KI bone marrow-derived macrophage cultures show decreased osteoclastogenesis. Despite the hyperostotic phenotype, bone matrix in Ank KI/KI mice is hypomineralized and less mature, indicating that biomechanical properties of bones may be compromised by the Ank mutation. We believe this new mouse model will facilitate studies of skeletal abnormalities in CMD at cellular and molecular levels.

show abstract

Section: Resultsmentioning

confidence: 78%

Introduction of a Phe377del Mutation in ANK Creates a Mouse Model for Craniometaphyseal Dysplasia

Chen

Wang

Strecker

et al. 2009

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…[6] Surgical results in this condition are inconsistent, as reported in literature. [4,6,8,[10][11][12] Reports are available stating rapid bone growth following surgery. [6] Optic nerve decompression has been reported in literature but the results are not encouraging, with reduction of vision and blindness reported after optic canal decompression.…”

Section: Discussionmentioning

confidence: 99%

Craniofacial surgery for craniometaphyseal dysplasia

2006

View full text Add to dashboard Cite

Craniometaphyseal dysplasia (CMD) is a rare congenital bone dysplasia with abnormal bony overgrowth leading to characteristic facial features and cranial nerve compression. We present a 10-year-old child with bony swelling at the nasal root since birth along with decreased hearing in both ears. She had normal developmental milestones and intelligence. On examination, she had bossing of forehead with very broad nasal root, short septum, hypertelorism and epicanthic folds. CT scan with 3D reconstruction revealed grossly thickened calvarium and hyperostosis and sclerosis of the cranial base. As the major concern of the parents was cosmetic, craniofacial reconstruction was performed with good cosmetic outcome.

show abstract

“…Additional common radiographic findings in patients with CMD include hyperostosis of the cranial base, narrowing of the foramina, and osseous obliteration of paranasal sinuses and mastoid air cells. In addition to facial bone deformities, patients may have facial paralysis and blindness as a result of cranial nerve compression and hearing loss secondary to a constricted nerve or internal auditory canals [Sheppard et al, 2003a,b; Kim et al, 2005].…”

Section: Introductionmentioning

confidence: 99%

Novel ANKH mutation in a patient with sporadic craniometaphyseal dysplasia

Zajac

Baek

Salhab

et al. 2010

American J of Med Genetics Pt A

View full text Add to dashboard Cite

Craniometaphyseal dysplasia is caused by mutations in ANKH (ankylosis, progressive homolog (mouse)) in the majority of cases, and all of the reported mutations are single amino acid changes. Genomic DNA from an affected patient, his biological parents and a sibling was amplified and ANKH was sequenced. The affected patient had a complex heterozygous mutation in exon 7 (c.936T>C, c.938C>G, c.942_953delTGGTTGACGGAA), predicting p.Try290Gln and p.Trp292_Glu295del. We studied the effect of the predicted mutation on the subcellular distribution of ANKH protein. Immunofluorescent labeling of COS-7 cells transduced with normal or mutant Ank (murine progressive ankylosis), showed that normal Ank localized to both the plasma membrane and cytoplasm, while mutant Ank was detected only in the cytoplasmic compartment. We propose that this craniometaphyseal dysplasia mutation causes a loss of ANKH protein expression and activity in the plasma membrane due to aberrant intracellular protein trafficking.

show abstract

Craniometaphyseal dysplasia: a case report and review of medical and surgical management

Cited by 16 publications

References 25 publications

Introduction of a Phe377del Mutation in ANK Creates a Mouse Model for Craniometaphyseal Dysplasia

Introduction of a Phe377del Mutation in ANK Creates a Mouse Model for Craniometaphyseal Dysplasia

Craniofacial surgery for craniometaphyseal dysplasia

Novel ANKH mutation in a patient with sporadic craniometaphyseal dysplasia

Contact Info

Product

Resources

About