Bruck syndrome is characterized by congenital contractures with pterygia, onset of fractures in infancy or early childhood, postnatal short stature, severe limb deformity, and progressive scoliosis (McPherson and Clemens, 1997).
- Genetic Heterogeneity of Bruck Syndrome ... Bruck syndrome is characterized by congenital contractures with pterygia, onset of fractures in infancy or early childhood, postnatal short stature, severe limb deformity, and progressive scoliosis (McPherson and Clemens, 1997). - Genetic Heterogeneity of Bruck Syndrome Bruck syndrome-2 (609220) is caused by homozygous mutation in the PLOD2 gene (601865) on chromosome 3q23-q24. Van der Slot et al. (2003) stated that they were unaware of any phenotypic differences between the 2 forms of Bruck syndrome.
Viljoen et al. (1989) described 5 children from 3 unrelated families who were born with symmetrical contractures of the knees, ankles, and feet. An initial diagnosis of arthrogryposis multiplex was made because of fractures following trivial trauma and ... Viljoen et al. (1989) described 5 children from 3 unrelated families who were born with symmetrical contractures of the knees, ankles, and feet. An initial diagnosis of arthrogryposis multiplex was made because of fractures following trivial trauma and wormian bones in skull radiographs. The sclerae and teeth were normal. One family contained 2 affected brothers and an affected sister. Of the 3 pairs of parents, all were nonconsanguineous. Viljoen et al. (1989) concluded that this disorder was reported in a single male by Bruck (1897) and therefore suggested that the disorder be called Bruck syndrome. Steinmann (1993) pointed out, however, that Bruck's patient had different progressive bone changes and secondary joint contractures occurring later than those in the patients of Viljoen et al. (1989). Webbing (pterygia) was present at the elbow and knee in the patients of Viljoen et al. (1989), supporting the view that lack of movement of the affected joints was present during embryologic development, possibly as early as the seventh week of gestation. Sharma and Anand (1964) reported an Indian boy with features of osteogenesis imperfecta and arthrogryposis multiplex congenita affecting the knee and ankle joints, plus bilateral talipes equinovarus. This child had blue sclerae. Brenner et al. (1993) described a male patient with osteogenesis imperfecta who was born with contractures of the knee, elbow, and ankle joints. During the first 4 years he suffered from recurrent fractures. He had white sclerae, mild dentinogenesis imperfecta, multiple wormian bones, severe scoliosis, and short stature. Collagen fibrils of the osteoid had a varying diameter, a feature not found in typical osteogenesis imperfecta patients. Analysis of compact bone showed that the size of apatite crystals and the extractability of collagen with pepsin were markedly elevated compared to controls and patients with osteogenesis imperfecta type III (259420) or IV (166220). McPherson and Clemens (1997) described a male patient who was born with flexion contractures and pterygia at the elbows, clubfeet, torticollis, and several rib fractures. During infancy and childhood, multiple fractures of the lower limbs occurred with minimal trauma and led to disabling deformities. When evaluated at age 19 years, he was normally intelligent, but very short, with severe kyphoscoliosis compromising pulmonary function. Pterygia limited elbow extension to 90 degrees, and severe lower limb deformities prevented walking. He did not have blue sclerae, dentinogenesis imperfecta, or hearing loss. X-ray studies showed demineralized bones, severe deformity, and cystic change at old fracture sites, as well as vertebral wedging. He died at age 21 of restrictive lung disease. Breslau-Siderius et al. (1998) reported a family in which 3 children of first-cousin Kurdish parents had Bruck syndrome. The 12-year-old proposita had severe contractures of the knee and ankle without reports of bone fractures, kyphosis, scoliosis, popliteal webbing, and local hypermobility in the wrists and fingers. Her 7-year-old sister had recurrent fractures of the femurs, local hypermobility in the wrist and finger joints, severe contractures at the hips, knees, and ankles, scoliosis, and kyphosis. Her 2-year-old brother had contractures of the hips and right knee, and there was no webbing. Shaheen et al. (2010) described 2 brothers with Bruck syndrome. As a neonate, the index patient had severe flexion deformity of knees, ankles, and, to a lesser extent, elbows. At age 7 months, he had a fracture of the femur as a result of trivial trauma, followed by multiple other long bone fractures in early childhood. He had normal appearance of the sclera and teeth. At the age of 9 years, he was still unable to walk but had normal use of his hands. His radiologic features consisted of evidence of old healed fractures, severe flexion deformities of knees and ankles, wormian bones, and generalized osteopenia. His similarly affected 13-year-old brother had frequent fractures and multiple joint contractures. Both children were treated with parenteral bisphosphonate, which reduced fracture frequency.
In 2 brothers with Bruck syndrome, Shaheen et al. (2010) identified a homozygous 8-bp insertion in the FKBP10 gene (607063.0003). They suggested that their patients and the patients reported by Alanay et al. (2010) with osteogenesis imperfecta may ... In 2 brothers with Bruck syndrome, Shaheen et al. (2010) identified a homozygous 8-bp insertion in the FKBP10 gene (607063.0003). They suggested that their patients and the patients reported by Alanay et al. (2010) with osteogenesis imperfecta may both have had Bruck syndrome and that bisphosphonate therapy may explain the less severe phenotype in their patients. In response to Shaheen et al. (2010), Alanay and Krakow (2010) noted that a wide phenotypic range of severity can result from different mutations in the same gene and suggested that the disorder caused by mutation in the FKBP10 gene be categorized as a recessive form of progressive deforming OI with or without joint contractures. Kelley et al. (2011) sequenced the FKBP10 gene in 6 individuals from 5 families with a moderately severe OI phenotype, 4 with joint contractures, including the patient reported by Viljoen et al. (1989), and 1 (patient 2) without congenital joint contractures, and identified homozygous or compound heterozygous mutations in all. In 2 sibs, one with and one without contractures, they identified homozygosity for a previously identified frameshift mutation (607063.0002). Shaheen et al. (2011) described a consanguineous Saudi family with Bruck syndrome in which 3 sisters and 2 male cousins had the same novel mutation in the FKBP10 gene (743dupC; 607063.0007). Four of those affected did not have contractures; the fifth had abnormal skin folds at the popliteal area that caused flexion contractures of the knees, which were noticed at birth, and he later had frequent fractures. Puig-Hervas et al. (2012) screened for mutations in 6 consanguineous unrelated Egyptian families with Bruck syndrome and identified homozygous mutations in the FKPB10 gene in 2 families and in the PLOD2 gene (601865) in 4 families (see BRKS2; 609220). Two probands had the same insertion/deletion mutation in the FKBP10 gene (607063.0009).