Fibrochondrogenesis is a severe, autosomal recessive, short-limbed skeletal dysplasia clinically characterized by a flat midface with a small nose and anteverted nares, significant shortening of all limb segments but relatively normal hands and feet, and a small bell-shaped ... Fibrochondrogenesis is a severe, autosomal recessive, short-limbed skeletal dysplasia clinically characterized by a flat midface with a small nose and anteverted nares, significant shortening of all limb segments but relatively normal hands and feet, and a small bell-shaped thorax with a protuberant abdomen. Radiographically, the long bones are short and have broad metaphyseal ends, giving them a dumb-bell shape. The vertebral bodies are flat and, on lateral view, have a distinctive pinched appearance, with a hypoplastic posterior end and a rounded anterior end. The ribs are typically short and wide and have metaphyseal cupping at both ends (summary by Tompson et al., 2010). - Genetic Heterogeneity of Fibrochondrogenesis Fibrochondrogenesis-2 (FBCG2; 614524) is caused by mutation in the COL11A2 gene (120290) on chromosome 6p21.3.
Fibrochondrogenesis is a rare, often neonatally lethal, rhizomelic chondrodysplasia distinguished from other forms of lethal dwarfism by broad long-bone metaphyses, pear-shaped vertebral bodies, and characteristic microscopic changes of cartilage: unique interwoven fibrous septa and fibroblastic dysplasia of chondrocytes. ... Fibrochondrogenesis is a rare, often neonatally lethal, rhizomelic chondrodysplasia distinguished from other forms of lethal dwarfism by broad long-bone metaphyses, pear-shaped vertebral bodies, and characteristic microscopic changes of cartilage: unique interwoven fibrous septa and fibroblastic dysplasia of chondrocytes. Lazzaroni-Fossati et al. (1978) first described this disorder in an infant from an uncle-niece marriage; a previously born sib apparently was identically affected. Whitley et al. (1984) described 2 unrelated cases in full detail. Eteson et al. (1982, 1984) also detailed 2 unrelated cases, 1 Japanese and 1 Italian. Hunt and Vujanic (1998) presented a case of fibrochondrogenesis diagnosed in a fetus of 17 weeks, the youngest patient reported to that time. The fetus showed severe micrognathia and bifid tongue, 2 manifestations not previously described. Tompson et al. (2010) reported 3 patients, 2 of whom were sibs, with fibrochondrogenesis. The proband from one family was the first child of parents of European descent and was stillborn at 32 weeks of gestation. The proband from the second family was the second affected child born to a father of European descent and an African American mother. The pregnancy for the first affected child was terminated at 24 weeks' gestation, whereas the second affected child was born at term. Although the radiographs supported a diagnosis of fibrochondrogenesis in both affected offspring, the clinical phenotype of the second child was milder than previously reported for fibrochondrogenesis and he was 3 years of age at the time of report. He had a flat midface, prominent eyes, short stature, and short limbs, and his hands exhibited brachyclinodactyly with some soft tissue syndactyly in the web spaces. His trunk was short and narrow, he had a pectus carinatum, and he was able to breathe without assistance. He had high myopia, a left cataract, and mild to moderate hearing loss. The parents in both families had myopia or hearing loss or both.
Tompson et al. (2010) sequenced the COL11A1 gene (120280) in 2 unrelated patients with fibrochondrogenesis and demonstrated that each was a compound heterozygote for a loss-of-function mutation on one allele and a mutation predicting substitution for a conserved ... Tompson et al. (2010) sequenced the COL11A1 gene (120280) in 2 unrelated patients with fibrochondrogenesis and demonstrated that each was a compound heterozygote for a loss-of-function mutation on one allele and a mutation predicting substitution for a conserved triple-helical glycine residue on the other (120280.0008-120280.0011). The parents who were carriers of a missense mutation had myopia. Early-onset hearing loss was noted in both parents who carried a loss-of-function allele. Tompson et al. (2010) suggested that COL11A1 is a locus for mild, dominantly inherited hearing loss and that there might be phenotypic manifestations among carriers.
Among the 1,158,067 live births registered by the Spanish Collaborative Study of Congenital Malformations (ECEMC), Martinez-Frias et al. (1996) encountered a case of fibrochondrogenesis. This was supposedly the eighth reported case. The frequency in this series should be ... Among the 1,158,067 live births registered by the Spanish Collaborative Study of Congenital Malformations (ECEMC), Martinez-Frias et al. (1996) encountered a case of fibrochondrogenesis. This was supposedly the eighth reported case. The frequency in this series should be considered a minimal prevalence for live births.