Fibular A/hypoplasia: Review and documentation of the fibular developmental field

Abstract

Fibular aplasia and/or hypoplasia is documented as a developmental field defect and the extent of the fibular developmental field is delineated. The term fibular a/hypoplasia denotes the clinical spectrum of fibular deficiency in different patients and also implies that aplasia can be present in one limb and hypoplasia in the other. Causal heterogeneity of fibular a/hypoplasia is demonstrated, thereby defining it as a developmental field defect. Most cases of fibular a/hypoplasia are isolated, sporadic events. An autosomal dominant form of isolated fibular a/hypoplasia with ankle joint anomaly is reviewed. Fibular a/hypoplasia may be part of more complex sporadic dysostoses; sporadic syndromes, an aneuploidy syndrome; several autosomal dominant and autosomal recessive conditions. Fibular a/hypoplasia is also postulated to occur as a result of disruption or teratogenic insult; in animals, fibular development can be disturbed by radiation, busulfan, and retinoic acid. Clinical data allow evaluation of the extent of the fibular developmental field of the lower limb. This appears to include the pubic portion of the pelvis, proximal femur (distal half being apparent tibial developmental territory), patella, anterior cruciate ligament, and lateral and/or axial foot rays (but “never” the hallux and almost never associated with polydactyly). The rare cases of fibuloulnar dimelia allow confirmation of the well known homology of mesomelic limb segments responsible for concordant ulnar and fibular (and radial and tibial) defect, if both upper and lower limbs are involved in a given condition. Because fibular a/hypoplasia is the commonest of the mesomelic paraxial hemimelias, is usually nonsyndromal, and in most cases is apparently nongenetic (ie, with negligible recurrence risk), we propose that in humans, as in several other tetrapods, the fibula is undergoing regressive evolution and hence is developmentally especially labile.

New mesomelic dysplasia with absent fibulae and triangular tibiae

“…Fibular aplasia may be seen in a number of conditions with marked causal heterogeneity, which has given rise to the postulation of a "fibular developmental field" [Lewin and Opitz, 1986]. The presence of tibial and radial defects, in addition to bilateral aplasia of the fibulae seen in our cases, would argue against them having such a "field defect."…”

“…The presence of tibial and radial defects, in addition to bilateral aplasia of the fibulae seen in our cases, would argue against them having such a "field defect." Various teratogens have been previously reported to cause limb abnormalities, including fibular aplasia or hypoplasia [Lewin and Opitz, 1986], but no such exposures were reported in these cases and selective shortness of the middle segments alone would not be expected.…”

Familial aplasia/hypoplasia of pelvis, femur, fibula, and ulna with abnormal digits in an inbred Pakistani Muslim family: A possible new autosomal recessive disorder with overlapping manifestations of the syndromes of Fuhrmann, Al-Awadi, and Raas-Rothschild

“…The survey of Westin and Gunderson [1969] documented absence of the fibula in more than half of the cases, approximately one quarter with upper limb abnormalities and the remaining one-fourth with variable limb defects. It has been reasonably argued that PFFD and FFU are the same condition [Lenz and Feldman, 1977], probably related to the fibular developmental field [Lewin and Opitz, 1986;Sorge et al, 1995]. A genetic basis of FFU syndrome was first suggested by Zlotogora et al [1983], who described two sibs affected with the FFU complex, raising the possibility of autosomal recessive inheritance.…”

Analysis of a new allele of limb deformity (ld) reveals tissue- and age-specific transcriptional effects of the Ld Global Control Region

“…Many human syndromes might be considered analogous to the ld mutation in mice, including syndromes such as Renal Dysplasia-Limb Defects Syndrome (OMIM 266910), Fibuloulnar Aplasia/Hypoplasia With Renal Abnormalities (OMIM 228940), or Brachydactyly-Ectrodactyly With Fibular Aplasia/Hypoplasia (OMIM 113310) (McKusick, 2003). In fact, any of the human syndromes associated with fibular dysplasia (Lewin and Opitz, 1986), one of the striking features of the ld mice, might be an analogous human syndrome. The identification of one of these (or other) syndromes as an ld analog would await the identification of a FMN1 or GREM1 mutation in one of these extremely rare patients.…”