Developmental Dysplasia Of The Hip 1

Description

Congenital dysplasia of the hip (CDH) is an abnormality of the seating of the femoral head in the acetabulum. Its severity ranges from mild instability of the femoral head with slight capsular laxity, through moderate lateral displacement of the femoral head, without loss of contact of the head with the acetabulum, up to complete dislocation of the femoral head from the acetabulum. It is one of the most common skeletal congenital anomalies (summary by Sollazzo et al., 2000).

Acetabular dysplasia is an idiopathic, localized developmental dysplasia of the hip that is characterized by a shallow hip socket and decreased coverage of the femoral head. Its radiologic criteria include the center-edge angle of Wiberg, the Sharp angle, and the acetabular roof obliquity. Most patients with acetabular dysplasia develop osteoarthritis (165720) after midlife, and even mild acetabular dysplasia can cause hip osteoarthritis (summary by Mabuchi et al., 2006).

CDH occurs as an isolated anomaly or with more general disorders represented by several syndromes and with chromosomal abnormalities such as trisomy 18 (Wynne-Davies, 1970).

Genetic Heterogeneity of Developmental Dysplasia of the Hip

Developmental dysplasia of the hip-1 (DDH1) maps to chromosome 13q22; DDH2 (615612) maps to chromosome 3p21.

Clinical Features

Mabuchi et al. (2006) described a large Japanese family in which acetabular dysplasia inherited as an autosomal dominant was the basis of osteoarthritis of the hip joint. Eight individuals in 4 generations had acetabular dysplasia manifested as pain in the hip joint during adolescence and progressing to severely crippling hip osteoarthritis before age 60 years. The patients were in general good health, height was not reduced, and there was no skeletal involvement suggestive of chondrodysplasia. Hip osteoarthritis was indistinguishable from that of idiopathic nonfamilial osteoarthritis associated with acetabular dysplasia. The family's phenotype resembled that of Beukes familial hip dysplasia (142669) in that both exhibited shallow acetabula and eventual osteoarthritis. However, the later onset of symptoms, lack of deformity in the femoral head and/or greater trochanter, and absence of broadening of the femoral neck distinguished the phenotype of the Japanese family from that of Beukes familial hip dysplasia.

Mapping

Mabuchi et al. (2006) performed genomewide screening in a Japanese family with acetabular dysplasia and osteoarthritis and observed linkage to chromosome 13q22. Haplotype analysis narrowed the locus to a 6.0-cM interval, with a maximum multipoint lod score of 3.57.

Population Genetics

There is a great discrepancy in the frequency of CDH according to geographic and ethnic differences. In general, CDH is more frequent in whites than in blacks and Chinese (Weinstein, 1987; Wilkinson, 1992). For Caucasian populations, an incidence of 1 per 1,000 live births can be assumed (Warkany, 1985). Record and Edwards (1958) estimated the risk of recurrence in subsequently born sibs to be about 5%. CDH, often bilateral, is more frequent in females than in males, with a 5:1 ratio (Weinstein, 1987). Joint laxity, normally greater in females than in males, probably accounts for the preponderance of affected females over males.

Feldman et al. (2013) stated that there are well-defined areas of high prevalence of DDH in Japan as well as in Italy and other Mediterranean countries.

Inheritance

The Japanese family of Mabuchi et al. (2006) with acetabular dysplasia exhibited transmission consistent with autosomal dominant inheritance.

Autosomal dominant inheritance was favored by Bornfors et al. (1964). Horton et al. (1979) observed a kindred in which 16 males and 16 females in 6 generations were affected. There were several examples of male-to-male transmission. In 27 family members, hip dislocation was associated with joint laxity. Five had joint laxity only. Six obligate heterozygotes showed no abnormality.

In Ferrara, Italy, CDH has an usually high frequency, for which reason there has been keen awareness of the problem and need for early diagnosis and treatment. For that purpose a special center for the study of CDH was established in the 1930s. Sollazzo et al. (2000) performed a complex segregation analysis in a sample of 171 pedigrees collected through probands affected by nonsyndromic dysplasia of the hip treated in the Ferrara CDH Centre between 1991 and 1996. Analysis favored a 2-locus model, in which the accepted segregation model at the major locus was compatible with recessive transmission, with a gene frequency of the deleterious allele of approximately 0.20. For the other locus, among the mendelian hypotheses tested, the recessive model turned out to be the most parsimonious.

History

A classic article by Perkins (1928) on signs by which to diagnose congenital dislocation of the hip was excerpted by Peltier (1992).

Carter and Wilkinson (1964) postulated the existence of 2 genetic systems responsible for the etiology of CDH: the former, polygenic, related to dysplasia of the acetabulum; the latter, probably dominant, controlling the capsule around the hip joint. Wynne-Davies (1970), in accordance with this hypothesis, suggested that 2 etiologic groups with congenital dislocation of the hip can be observed: one group with acetabular dysplasia, inherited through a multiple gene system (and responsible for a high proportion of cases diagnosed late), and another group with joint laxity (responsible for a high proportion of neonatal cases), revealing a genetic predisposition in which the action of unknown environmental factors appeared to be important.

Animal Model

Hip dysplasia with dislocation occurs in high frequency in the German shepherd dog (Bornfors et al., 1964).