Geleophysic Dysplasia 2

A number sign (#) is used with this entry because of evidence that geleophysic dysplasia-2 (GPHYSD2) is caused by heterozygous mutation in exon 41 or 42 of the FBN1 gene (134797) on chromosome 15q21.1.

Acromicric dysplasia (ACMICD; 102370) and the autosomal dominant form of Weill-Marchesani syndrome (608328) are allelic to geleophysic dysplasia-2 and share overlapping skeletal and joint features.

For a general phenotypic description and discussion of genetic heterogeneity of geleophysic dysplasia, see 231050.

Molecular Genetics

In 19 patients with geleophysic dysplasia who were known to be negative for mutation in the ADAMTSL2 gene (612277), Le Goff et al. (2011) performed exome sequencing followed by candidate gene analysis and identified heterozygosity for 8 different mutations in the FBN1 gene (see, e.g., 134797.0055-134797.0058). Two of the mutations were also found in heterozygosity in patients with acromicric dysplasia, a disorder also characterized by short stature, short hands and feet, joint limitations, and skin thickening, but without cardiac involvement or early death. Le Goff et al. (2011) concluded that geleophysic dysplasia and acromicric dysplasia are clinically distinct but allelic conditions.

Passarge et al. (2016) stated that all FBN1 mutations resulting in GPHYSD2 or ACMICD have been found in exon 41 or 42. These exons encode the TGF-beta-binding protein-like domain-5 (TB5) (Le Goff et al., 2011).