Congenital malformations, deformations and chromosomal abnormalities
Congenital malformations and deformations of the musculoskeletal system
Autosomal recessive
11q13.4-q13.5
Autosomal recessive osteopetrosis (OP) is a rare, lethal disorder in which osteoclasts are absent or nonfunctional, resulting in a bone marrow cavity insufficient to support hematopoiesis.
The TCIRG1 gene, encoding the alpha-3 subunit of the vacuolar proton pump, which mediates the acidification of the bone/osteoclast interface, is responsible for more than one-half of the osteopetrosis patients.
| Subject ID | Country | Sex | Family History | Parental Consanguinity | HPO Terms | Variant | Zygosity | Mode of Inheritance | Reference | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|
| 259700.1 | Lebanon | Yes | Hepatosplenomegaly; Increased bone mine... Hepatosplenomegaly; Increased bone mineral density; Sclerosis of skull base; Frontal cortical atrophy; Temporal cortical atrophy; Hypochromic anemia; Pancytopenia  | NM_006019.3:c.702del | Homozygous | Autosomal, Recessive | Souraty et al. 2007 | |||
| 259700.2 | Lebanon | Yes | Hepatosplenomegaly; Increased bone miner... Hepatosplenomegaly; Increased bone mineral density; Thin ribs; Pathologic fracture | NM_006019.3:c.702del | Homozygous | Autosomal, Recessive | Souraty et al. 2007 | Has an older affecte... | ||
| 259700.3 | Syria | No | Increased bone mineral density; Optic at... Increased bone mineral density; Optic atrophy; Strabismus; Growth delay; Anemia | NM_006019.3:c.1421C>A | Homozygous | Autosomal, Recessive | Souraty et al. 2007 |
In a 5-year prospective study for newborns at Al Ain Medical District, Al-Gazali et al. (2003) identified one case, born to a consanguineous parents, who had autosomal recessive osteopetrosis. The study exhibited a cohort of 88% Arabs.
Paulose et al. (1988) described a case of osteopetrosis in a child who had agenesis of all paranasal sinuses as a silent feature of the disease.
Abdel-Al et al. (1994) diagnosed 19 Arab children (six boys and 13 girls) in ten sibships as having osteopetrosis over a 5-year period in various hospitals in Kuwait. Eighteen patients had an isolated autosomal recessive form.
In two Palestinian Muslim consanguineous families that lived in the same village, Dudin and Rambaud-Cousson (1993) found seven cases of lethal infantile osteopetrosis.
In a survey of 2000 different Palestinian Arab families Zlotogora (1997) found a high prevalence of recessive osteopetrosis.
Shalev et al. (2001) used linkage analysis for the prenatal diagnosis of osteopetrosis in Bedouin families at risk. Twelve cases were diagnosed, three fetuses were found to be affected, and one of the pregnancies was terminated.
Rysavy et al. (2007) described four relatives who presented with fractures and myelodysplatic anemia.
Al-Rasheed et al. (1998) observed, over a 10-year period, 28 Arab children with autosomal recessive osteopetrosis in two hospitals in Riyadh.