Burns et al. (1978) described a form of osteopetrosis resembling the autosomal dominant form (see OPTA2, 166600) in its benignity but displaying autosomal recessive inheritance. The clinical features were variable but included mandibular prognathism, genu valgum, anemia, hepatosplenomegaly, ... Burns et al. (1978) described a form of osteopetrosis resembling the autosomal dominant form (see OPTA2, 166600) in its benignity but displaying autosomal recessive inheritance. The clinical features were variable but included mandibular prognathism, genu valgum, anemia, hepatosplenomegaly, and tendency to fracture and mandibular osteomyelitis. Dental anomalies included retention of deciduous teeth, malformation of crowns, and strong tendency to caries. Kahler et al. (1984) gave a definitive description of this family. McClure (1978) reported a relatively mild form of recessive osteopetrosis in 3 sibs. One died at age 17; the 2 others were surviving at ages 20 and 16. Features included optic atrophy with blindness from an early age, gross bone deformities, numerous fractures, marked hepatosplenomegaly, and severe anemia and thrombocytopenia. The oldest, a male, attended university and majored in music. Splenectomy was performed in him at age 14 with partial relief of pancytopenia and the mechanical burden. The hemoglobin ran about 4 gm% for many years in all the children but, in the teens in the nonsplenectomized children, rose spontaneously, reaching about 9 gm% in the male who died. Horton et al. (1980) described 2 brothers with a mild form of osteopetrosis. There was no evidence of clinically important encroachment upon the bone marrow or cranial nerve foramina. Skeletal radiographs showed mild generalized increase in bone density, metaphyseal modeling defects affecting primarily the distal femurs, and coxa vara. Bone biopsy in both brothers showed wider than normal bony trabeculae which throughout the biopsy contained a core of cartilage, a slightly reduced marrow space, and, in contrast to established forms of osteopetrosis in which there is an increased number of osteoclasts, a normal to slightly reduced number of osteoclasts. The resting cartilage, growth plate, and chondroosseous junction appeared normal in both cases. The authors noted that autosomal or X-linked recessive inheritance was possible. Schimke (1994) provided an update on these brothers at the age of 21 and 18 years: one had suffered bilateral hip fractures and the other a unilateral fracture; both had some orthodontic problems with unerupted teeth; and neither had evidence of cranial nerve encroachment. Sobacchi et al. (2007) studied 6 patients from 4 families with autosomal recessive osteopetrosis in whom bone biopsy specimens showed absence of osteoclasts. The patients had severe osteopetrosis but slower disease progression compared to 'classic' osteopetrosis, with the 2 oldest patients alive at ages 11 and 12 years, respectively. Clinical features included hydrocephalus, visual impairment, mild to moderate hepatosplenomegaly, bone fractures, and poor bone remodeling. Three patients had undergone hematopoietic stem cell transplantation with good engraftment but no improvement in bone remodeling, suggesting a defect that was not intrinsic to osteoclasts.
In 6 patients from 4 families with an osteoclast-poor form of osteopetrosis who were negative for mutations in 3 genes known to cause the infantile malignant form of osteopetrosis (TCIRG1, 604592; CLCN7, 602727; and OSTM1, 607649), Sobacchi et ... In 6 patients from 4 families with an osteoclast-poor form of osteopetrosis who were negative for mutations in 3 genes known to cause the infantile malignant form of osteopetrosis (TCIRG1, 604592; CLCN7, 602727; and OSTM1, 607649), Sobacchi et al. (2007) identified 3 different homozygous mutations in the TNFSF11 gene: a 5-bp deletion (602642.0001) in a consanguineous Tunisian family, a missense mutation (M199K; 602642.0002) in 2 Sikh families, and a 2-bp deletion (602642.0003) in a consanguineous Kurdish family.