Brachydactyly C, short stature, and hip dysplasia

Fitch, Naomi; Jequier, Sigrid; Costom, Bruce H.

doi:10.1002/ajmg.1320040208

Cited by 8 publications

(4 citation statements)

References 13 publications

(2 reference statements)

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“…These include developmental dysplasia of the hip (family B, II‐4), severe bilateral vertical talus (family B, II‐2, II‐4) and bilateral radial head dislocations (family A, III‐1, III‐2). These nondigital skeletal abnormalities have been described in the past in association with BDC [Steinbach and Brown, 1969; Fitch, 1979; Fitch et al, 1979]. These findings are consistent with the key role CDMP‐1 plays in development and growth of the human skeleton and reinforces the need for thorough clinical and radiographic evaluation of the entire skeleton in individuals with BDC.…”

Section: Discussionsupporting

confidence: 80%

“…Two of these nonpenetrant members (family C; I‐2, II‐2) presented with what had been regarded as “constitutional” short stature with no other skeletal abnormalities. Short stature in association with BDC has been well recognized in the past and authors have commented on the impression that individuals with BDC appear shorter than their unaffected sibs [Fitch, 1979; Fitch et al, 1979]. These observations are consistent with data demonstrating that CDMP‐1 expression and activity appears to be an important factor in determining the size of skeletal elements by influencing chondrocyte proliferation [Francis‐West et al, 1999].…”

Section: Discussionsupporting

confidence: 54%

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Broad phenotypic spectrum caused by an identical heterozygous CDMP‐1 mutation in three unrelated families

Savarirayan

White

Goodman³

et al. 2002

American J of Med Genetics Pt A

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CDMP-1, a cartilage-specific member of the TGFss superfamily of secreted signaling molecules, plays a key role in chondrogenesis, growth and patterning of the developing vertebrate skeleton. Homozygous CDMP-1 mutations cause Hunter-Thompson and Grebe types of acromesomelic chondrodysplasia and DuPan syndrome in humans, as well as brachypodism in mice, while heterozygous mutations cause brachydactyly type C (BDC). We present clinical and radiographic data from three unrelated families in which 12 members share the same heterozygous CDMP-1 mutation, an insertion (insG206), resulting in a frameshift predicted to cause functional haploinsufficiency. Although eight mutation carriers display BDC, four have normal hands and feet, confirming nonpenetrance of BDC with CDMP-1 mutations. In addition, several carriers have other skeletal abnormalities, including severe bilateral vertical talus (in two), developmental hip dysplasia (in one), and short stature (in two, who are otherwise unaffected). Premature vertebral end-plate disease was observed in four mutation carriers and was associated with spondylolysis and spondylolisthesis in three of these. Axial skeletal involvement has not been previously reported in association with CDMP-1 mutations. This finding is consistent with CDMP-1 expression in human hypertrophic chondrocytes, which are present in the ring epiphyses of vertebral end plates. Phenotypic variation in BDC has previously been attributed either to locus heterogeneity or to the varied functional effects of different CDMP-1 mutations. The remarkable range of phenotypes caused by this identical CDMP-1 mutation in these families emphasizes the crucial role of genetic background, stochastic variation and/or environmental factors in modifying the observed phenotype. Our findings illustrate that nonpenetrance for the typical features of BDC can be appreciable and that atypical skeletal features that have been reported in some patients with BDC (i.e., clubfoot, short stature, spondylolysis) may also result from CDMP-1 mutation.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 54%

Broad phenotypic spectrum caused by an identical heterozygous CDMP‐1 mutation in three unrelated families

Savarirayan

White

Goodman³

et al. 2002

American J of Med Genetics Pt A

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“…Shortening and inward rotation of halluces was present in one patient and metacarpals were shortened in two affected individuals. No other accompanying skeletal or non‐skeletal features were present as reported in other BDC kindreds, particularly no talipes valgus [Haws, 1963], Perthes disease [Robinson et al, 1968], hip dysplasia [Fitch et al, 1979a], small cup‐shaped ears [Rowe‐Jones et al, 1992], or spine deformities [Savarirayan et al, 2003]. Short stature was observed in some members of the family but appeared to occur independently from the mutation status.…”

Section: Discussionmentioning

confidence: 99%

Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1

Schwabe

Türkmen

Leschik

et al. 2003

American J of Med Genetics Pt A

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Brachydactyly type C (BDC) is characterized by shortening of the middle phalanges of the index, middle, and little finger with hyperphalangy, usually of the index and middle finger. Heterozygous mutations of the cartilage derived morphogenetic protein-1 (CDMP1) resulting in a loss of function have been reported in BDC. We here describe a large kindred with a semi-dominant form of BDC and pronounced ulnar deviation of the second and third digits. In this family a novel homozygous missense mutation was identified (517A > G) changing methionine to valine at amino acid position 173. The mutation is located within a highly conserved seven amino acid region of the prodomain of CDMP1. Hand radiographs of heterozygous mutation carriers showed mild shortening of the metacarpals IV and V; a finding confirmed by the analysis of their metacarpophalangeal profiles (MCPPs). The mutation described here points toward an important function of the prodomain for the folding, secretion, and availability of biologically active CDMP1.

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“…According to this classification, type A, shortness in the middle phalanxes of the digits; type B, absence of or shortness of the mid and distal phalanxes of the digits together with deformity in the thumbs and big toes; type C, shortness in the mid and proximal phalanxes of the 2 nd and 3 rd fingers, hypersegmentation in the proximal pha- anomalies have been reported 6,7 . In the case presented here, a wide variability of brachydactyly with hand and foot involvement and thoracic wedging was found to contribute to the clinical phenotype.…”

Section: Discussionmentioning

confidence: 99%

Concomitance of type D and E brachydactyly: A case report

Koca¹

2015

Gaziantep Med J

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Here, we present of a 35-year old female diagnosed with an overlapping form of non-syndromic brachydactyly types D and E with phenotypic and radiological signs. There was observed to be shortening in the right hand metacarpal of 3 rd and 4 th fingers and left hand metacarpal of 4 th finger and left foot metatarsal of 4 th toe. There was also shortening of the distal phalanx of the thumbs and thoracic kyphosis. The syndromic form of brachydactyly type E is firmly associated with pseudo-hypopthyroidism as resistance to pthyroid hormone is the most prominent feature. As the patient had normal stature, normal laboratory parameters and no psychomotor developmental delay, the case was classified as isolated E type brachydactyly.

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Brachydactyly C, short stature, and hip dysplasia

Abstract: Short stature may be a component of the brachydactyly C syndrome. A family is presented in which the propositus has brachydactyly C, short stature, and hip dysplasia.

Cited by 8 publications

References 13 publications

Broad phenotypic spectrum caused by an identical heterozygous CDMP‐1 mutation in three unrelated families

Broad phenotypic spectrum caused by an identical heterozygous CDMP‐1 mutation in three unrelated families

Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1

Concomitance of type D and E brachydactyly: A case report

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