A number sign (#) is used with this entry because of evidence that fibrochondrogenesis-2 (FBCG2) is caused by homozygous or heterozygous mutation in the COL11A2 gene (120290) on chromosome 6p21.

Fibrochondrogenesis is a severe skeletal dysplasia characterized by a flat midface, short long bones, short ribs with broad metaphyses, and vertebral bodies that show distinctive hypoplastic posterior ends and rounded anterior ends, giving the vertebral bodies a pinched appearance on lateral radiographic views. The chest is small, causing perinatal respiratory problems which usually, but not always, result in lethality. Affected individuals who survive the neonatal period have high myopia, mild to moderate hearing loss, and severe skeletal dysplasia (summary by Tompson et al., 2012).

For a discussion of genetic heterogeneity of fibrochondrogenesis, see FBCG1 (228520).

Tompson et al. (2012) reported 2 unrelated probands with fibrochondrogenesis who died at birth. The first patient was born of first-cousin parents of Saudi Arabian descent; the couple previously had an affected child and 2 unaffected children. The clinical phenotype consisted of midface hypoplasia with a small nose and anteverted nares, significant shortening of all limb segments with relatively normal hands and feet, and a small thorax with protuberant abdomen. Radiographs showed characteristic findings of fibrochondrogenesis, including severe shortening of the long bones with very widened metaphyses, moderate platyspondyly, delayed ossification of the cervical vertebral bodies, ischia, and pubis, short-cupped ribs giving a bell-shaped appearance to the thorax, and small ilia with irregular metaphysis. The second patient, who was the offspring of a nonconsanguineous phenotypically normal couple, displayed the typical facial features of fibrochondrogenesis, including a relatively large skull with a wide anterior fontanel, midface hypoplasia with a small nose and anteverted nares, and micrognathia. In addition, there was significant shortening of all limb segments with relatively normal hands and feet, and a small thorax with protuberant abdomen. Radiographs showed platyspondyly, shortening of the long bones with widened metaphyses, a bell-shaped thorax and short ribs with metaphyseal cupping, and hypoplastic ischia, pubis, and ilia. A lateral view of the spine showed posteriorly narrowed vertebral bodies consistent with fibrochondrogenesis.

The transmission pattern of FBCG2 in the consanguineous family reported by Tompson et al. (2012) was consistent with autosomal recessive inheritance. The heterozygous mutation in the COL11A2 gene that was identified in a patient (R10-691A) with FBCG2 by Tompson et al. (2012) occurred de novo.

In a deceased infant with fibrochondrogenesis, who was born of consanguineous parents and known to be negative for mutation in the COL11A1 gene (120280), Tompson et al. (2012) performed whole-genome SNP genotyping and identified a 26.7-Mb block of homozygosity on chromosome 6p, a region containing the COL11A2 gene. Analysis of COL11A2 revealed homozygosity for a splice site mutation (120290.0012) that was present in heterozygosity in the unaffected parents and 1 unaffected sib. In another deceased infant with fibrochondrogenesis, born of nonconsanguineous healthy parents, who was known to be negative for mutation in the COL11A1 and COL2A1 (120140) genes, Tompson et al. (2012) identified a heterozygous 9-bp deletion in the COL11A2 gene (120290.0013). The mutation was shown to have occurred de novo.