ISCHEMIC NECROSIS OF FEMORAL HEAD
FEMORAL HEAD, ASEPTIC NECROSIS OF
OSTEONECROSIS OF FEMORAL HEAD
FEMORAL HEAD, AVASCULAR NECROSIS OF
ANFH
Familial osteonecrosis of the femoral head
Avascular necrosis of the femoral head (ANFH) is a debilitating disease that usually leads to destruction of the hip joint in the third to fifth decade of life (Mont and Hungerford, 1995). The disorder is characterized by progressive ... Avascular necrosis of the femoral head (ANFH) is a debilitating disease that usually leads to destruction of the hip joint in the third to fifth decade of life (Mont and Hungerford, 1995). The disorder is characterized by progressive pain in the groin, mechanical failure of the subchondral bone, and degeneration of the hip joint. Nearly one-half of patients require hip replacement before 40 years of age. ANFH represents a specific form of the broader disease category of osteonecrosis. It has been suggested that a common pathway of pathogenesis of ANFH involves the interruption of blood circulation to the anterior-superior-lateral part of the femoral head, leading to ischemic insult and bone collapse (Atsumi and Kuroki, 1992). The disease is aggravated by mechanical disruption, e.g., hip fracture (Bachiller et al., 2002); by external pressure on or damage to a vessel wall, e.g., vasculitis (Wang et al., 1988), radiation therapy (Massin and Duparc, 1995), and systemic lupus erythematosus (Abu-Shakra et al., 2003); arterial thrombosis or embolism, e.g., sickle cell disease (Milner et al., 1991); corticosteroid use (Fisher, 1978); and alcohol abuse (Wang et al., 2003). Although a major proportion of individuals with ANFH have underlying risk factors and are classified as having secondary ANFH, 15 to 30% of patients showing no apparent risk factors are classified as having primary or idiopathic ANFH (Assouline-Dayan et al., 2002). Some ANFH previously considered idiopathic may actually represent a feature of hereditary thrombophilia (an increased tendency for intravascular thrombosis) or hypofibrinolysis (a reduced ability to lyse thrombi). Deficiency of activated protein C (PROC; 612283) or protein S (PROS1; 176880), resulting in thrombophilia (176860; 612336), has been reported to be associated with osteonecrosis of the hip in adults and with LCP in children. Hypofibrinolysis, mediated by high levels of plasminogen activator inhibitor (PAI; 173360), has been cited as a major cause of idiopathic osteonecrosis.
Liu et al. (2005) identified 3 families in which there was autosomal dominant inheritance of ANFH, with mapping of the phenotype to 12q13. They carried out haplotype analysis in the families, selected candidate genes in the critical interval ... Liu et al. (2005) identified 3 families in which there was autosomal dominant inheritance of ANFH, with mapping of the phenotype to 12q13. They carried out haplotype analysis in the families, selected candidate genes in the critical interval for ANFH on 12q13, and sequenced the promoter and exonic regions of the type II collagen gene (COL2A1; 120140) from patients with inherited and sporadic forms of ANFH. The same gly1170-to-ser (120140.0043) mutation was found in 2 separate families, with the mutant allele occurring on different haplotype backgrounds. In the third family, a gly717-to-ser (120140.0044) mutation was detected. No mutation was found in the COL2A1 coding region in sporadic cases of ANFH. The authors pointed out that in families with ANFH, haplotype and sequence analysis of the COL2A1 gene can be used to identify carriers of the mutant allele before the onset of clinical symptoms, allowing the initiation of measures that may delay progression of the disease. In a 40-year-old man who was diagnosed with avascular necrosis of the femoral head at 18 years of age and who was negative for mutation in the COMP (600310), COL9A1 (120210), COL9A2 (120260), COL9A3 (120270), DTDST (606718), and MATN3 (602109) genes, Kannu et al. (2011) identified a heterozygous missense mutation in the COL2A1 gene (120140.0054) that was not found in unaffected family members or in 150 age-, sex-, and ethnicity-matched controls. The patient, who underwent bilateral hip replacement at age 33 years, had generalized osteoporosis by DEXA scan and a normal skeletal survey, other than bilateral hip degeneration. He had no facial dysmorphism, and ophthalmologic and audiologic examinations were normal. The patient's 2 sisters, who were of average stature, had normal skeletal radiographs; however, 1 of the sisters had a daughter diagnosed radiographically with multiple epiphyseal dysplasia at 10 years of age who was negative for mutation in COL2A1 and 6 other candidate genes. Because most COL2A1 mutations are private, Kannu et al. (2011) suggested that complete COL2A1 analysis should be considered in individuals presenting with early-onset degenerative hip disease.