U Irlenbusch1, Th Schäller. 1. Department of Orthopedic Surgery, Marienstift Arnstadt, Wachsenburgallee 12, D-99310 Arnstadt, Germany. irlenbusch@ms-arn.de
Abstract
OBJECTIVE: Until the current molecular genetic investigations, all available data concerning the genetic predisposition to Heberden's nodes are based on a single investigation by Stecher in the 1940s. There is controversy in the literature about the correlation between Heberden's nodes and generalized osteoarthritis (GOA). Our own epidemiological and clinical investigations support this correlation. Therefore, the question arises as to whether the remarkable inheritance described by Stecher is correct and whether Heberden's nodes can indeed be used as a genetic marker for GOA. METHODS: From our clinical trial on 106 patients with Heberden's arthritis, we could identify 88 families from index cases. Altogether, we included 931 family members over a maximum of four generations. First of all, the genealogical trees of the families were established. Subsequently, we examined the patients' hands in respect of Heberden's nodes and completed the genealogical trees during home visits. RESULTS: In the 88 families analyzed, 152 patients with manifest Heberden's arthritis were listed (26 males, 126 females). The genealogical analysis of 156 descendants (74 males, 82 females) of 93 patients with Heberden's nodes suggests autosomal dominant inheritance. In view of the age-related manifestation and age pattern of the descendants, we postulate a heterozygous manifestation for women (dominant gene action) and only a homozygous manifestation for men (recessive gene action). CONCLUSIONS: The genealogic analysis does not contrast with the quite remarkable inheritance described by Stecher but rather supports the hypothesis that manifestation is dominant in females and recessive in males. From our point of view, this heredity does not contradict latest genetic assays which show the possibility of genetic defects causing the hereditary osteoarthritis (OA).
OBJECTIVE: Until the current molecular genetic investigations, all available data concerning the genetic predisposition to Heberden's nodes are based on a single investigation by Stecher in the 1940s. There is controversy in the literature about the correlation between Heberden's nodes and generalized osteoarthritis (GOA). Our own epidemiological and clinical investigations support this correlation. Therefore, the question arises as to whether the remarkable inheritance described by Stecher is correct and whether Heberden's nodes can indeed be used as a genetic marker for GOA. METHODS: From our clinical trial on 106 patients with Heberden's arthritis, we could identify 88 families from index cases. Altogether, we included 931 family members over a maximum of four generations. First of all, the genealogical trees of the families were established. Subsequently, we examined the patients' hands in respect of Heberden's nodes and completed the genealogical trees during home visits. RESULTS: In the 88 families analyzed, 152 patients with manifest Heberden's arthritis were listed (26 males, 126 females). The genealogical analysis of 156 descendants (74 males, 82 females) of 93 patients with Heberden's nodes suggests autosomal dominant inheritance. In view of the age-related manifestation and age pattern of the descendants, we postulate a heterozygous manifestation for women (dominant gene action) and only a homozygous manifestation for men (recessive gene action). CONCLUSIONS: The genealogic analysis does not contrast with the quite remarkable inheritance described by Stecher but rather supports the hypothesis that manifestation is dominant in females and recessive in males. From our point of view, this heredity does not contradict latest genetic assays which show the possibility of genetic defects causing the hereditary osteoarthritis (OA).
Authors: C Pauli; R Whiteside; F L Heras; D Nesic; J Koziol; S P Grogan; J Matyas; K P H Pritzker; D D D'Lima; M K Lotz Journal: Osteoarthritis Cartilage Date: 2012-02-18 Impact factor: 6.576