Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) presenting with features of congenital contractural arachnodactyly

Abstract

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) in a 30-year-old woman is reported. At 21 weeks of pregnancy, routine fetal ultrasounds showed the presence of apparently isolated bilateral club feet. Fetal karyotyping documented an interstitial deletion of the long arm of chromosome 5: 46,XX,del(5) (q15q31) in all 50 analyzed metaphases. Because such deletion is associated with severe psychomotor retardation, the pregnancy was terminated. Postmortem karyotyping of skin fibroblasts confirmed the presence of this interstitial de novo deletion in all mitoses. The breakpoints on 5q were analyzed by fluorescent in situ hybridization and were localized at 5q15 and q31.1. This case illustrates the importance of fetal karyotyping in cases of isolated club feet. At autopsy, the fetus presented had minor anomalies and contractures of knee and hip joints. These clinical findings could fit the diagnosis of congenital contractural arachnodactyly (CCA) or Beals syndrome. CCA is caused by a defect in the fibrillin-2 (FBN2) gene. This gene was previously mapped on 5q23-31. Our molecular studies of both parents and the fetus, using an intragenic polymorphic GT repeat, showed that the FBN2 gene was deleted in the fetus and that the de novo interstitial deletion occurred on the paternally inherited chromosome 5. Thus, CCA may be caused by a loss of function of the FBN2 gene. Clinical findings in this fetus and those of other described cases with interstitial 5q deletions are reviewed, and similarities with CCA are stressed.

Genotype–phenotype correlation of a 5q22.3 deletion associated with craniofacial and limb defects

“…The common breakpoints of the interstitial 5q deletions were q15q31, q15q22 (or q15q21), q22q31, q23q31 and q22q23 (Table 1) (Courtens et al, 1998;Garcia-Miñaur et al, 2005;Harréus and Issing, 2002;Kadotani et al, 1984;Kobayashi et al, 1991;Lindgren et al, 1992;Rivera et al, 1987Rivera et al, , 1990Tzschach et al, 2006). Lindgren et al (1992) Fig.…”

“…Interestingly, almost all the cases with interstitial 5q deletions have not had the same breakpoints. Another explanation of the variability in the cases with interstitial 5q deletions and that apparently share the same deleted region is the possibility of incorrect assignment of the breakpoints (Courtens et al, 1998).…”

“…Clinical findings in cases with interstitial 5q deletions, reference to the criteria of both Courtens et al (1998) and Tzschach et al (2006) …”

“…It is difficult to accurately cytogenetically determine the deleted segment and the breakpoints because the banding pattern of the long arm of chromosome 5 is repetitious and it has three G-positive metaphase bands of almost equal size (q14, q21 and q23) (Courtens et al, 1998;Garcia-Miñaur et al, 2005). So far, 40 or more such cases have been reported and only a few cases have been analyzed by molecular cytogenetic methods (Tzschach et al, 2006).…”

Genetic Influences on Joint Contractures Secondary to Immobilization

“…Key mediators and pathways activated when the capsule lacks mechanical stimulus likely lead to these fibrotic changes. 6,9,18 Likewise, key mediators and pathways must actively counteract the effects of immobilization to preserve joint mobility. 18 Little is known about these mediators and their pathways.…”