Grebe syndrome: Clinical and radiographic findings in affected individuals and heterozygous carriers

Abstract

Grebe syndrome is a recessively inherited acromesomelic dysplasia. We studied, clinically and radiographically, 10 affected individuals, originating from Bahia, Brazil. The phenotype is characterized by a normal axial skeleton and severely shortened and deformed limbs, with a proximo-distal gradient of severity. The humeri and femora were relatively normal, the radii/ulnae and tibiae/fibulae were short and deformed, carpal and tarsal bones were fused, and several metacarpal and metatarsal bones were absent. The proximal and middle phalanges of the fingers and toes were invariably absent, while the distal phalanges were present. Postaxial polydactyly was found in several affected individuals. Several joints of the carpus, tarsus, hand, and foot were absent. Heterozygotes presented with a variety of skeletal manifestations including polydactyly, brachydactyly, hallux valgus, and metatarsus adductus. Grebe syndrome is caused by a missense mutation in the gene encoding cartilage-derived morphogenetic protein-1.

Characterization of an acromesomelic dysplasia, Grebe type case: novel mutation affecting the recognition motif at the processing site of GDF5

“…According to HGMD, about 34 mutations have been described in the CDMP1 gene to date, and these mutations had been associated with different phenotypes, specifically in the case of heterozygous missense mutations, ranging from mild brachydactyly with features overlapping to unaffected mutation carriers. The father of the proband manifested mild phenotypes related to the presence of a heterozygous mutation in the CDMP1 gene [1]. Homozygous mutations in the mature domain of GDF5 result in severe limb malformations such as AMDG or acromesomelic chondrodysplasia of Hunter-Thompson type.…”

“…In spite of this, the facial features and intelligence of the affected individuals are similar to those of the general population. In some cases, carriers also manifest milder signs such as brachydactyly and postaxial polydactyly [1]. Mutations in the CDMP1 gene have been associated with AMDG, autosomal recessive acromesomelic dysplasia of Hunter-Thompson type, autosomal recessive Abstract Acromesomelic dysplasia, Grebe type is a very rare skeletal dysplasia characterized by severe dwarfism with marked micromelia and deformation of the upper and lower limbs, with a proximodistal gradient of severity.…”

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

“…Distal skeletal elements are more severely affected by size reduction than proximal elements. Clinical manifestations in acromesomelic dysplasia Hunter-Thompson type (AMDH), Grebe type (AMDG), and Du Pan syndrome are overlapping with the most severe growth retardation in AMDG and with specific fibula malformation in Du Pan syndrome (Langer and Garrett 1980;Langer et al 1989;Costa et al 1998;Faiyaz-Ul-Haque et al 2002;Szczaluba et al 2005).…”

Homozygous Sequence Variants in the NPR2 Gene Underlying Acromesomelic Dysplasia Maroteaux Type (AMDM) in Consanguineous Families

“…AMDM is an autosomal recessive disorder that can be distinguished clinically from other types of acromesomelic dysplasias (Maroteaux et al, 1971;Langer et al, 1989;Costa et al, 1998). Clinical features of AMDM, reported in the patients, include disproportionate short stature with height below 120 cm and noticeable shortening of middle and distal segments of the skeleton (Maroteaux et al, 1971;Langer & Garrett, 1980).…”