A prehistoric example of polydactyly from the Iron Age site of Simbusenga, Zambia

Human burials, dated AD 1100-1500, were examined from the Iron Age site of Simbusenga, located some 35 miles northwest of Victoria Falls in Zambia. Pedal polydactyly was discovered in the fragmentary remains of a young adult of indeterminate sex aged 14-25. The preaxial form of polydactyly is indicated with bilateral involvement of the first metatarsals. There is incomplete hypoplastic duplication of both first metatarsals with broad heads for the metatarsal-phalangeal joints. No digital malformations were found in the other seven individuals with feet and/or hands from the site. Several studies point to autosomal dominance for cases of isolated polydactyly, but inheritance and patterning of preaxial polydactyly are still incompletely understood. The condition is also found in conjunction with genetic malformation syndromes such as Acrocephalypolysyndactyly, Lambotte, Oro-facio-digital, and VATER. High frequencies of polydactyly are reported for African and African-American populations, but further analysis reveals that the bulk of previously reported cases of polydactyly are representative of the postaxial form as opposed to the preaxial expression seen here.     

Prevention of polydactyly manifestation in Polydactyly Nagoya (Pdn) mice by administration of cytosine arabinoside during pregnancy

Male mice heterozygous for the dominant polydactyly gene Pdn (Polydactyly Nagoya) were crossed with normal or heterozygous females of the same strain. Pregnant females were treated with 5 mg/kg of cytosine arabinoside (Ara-C) on day 12 of gestation. The offspring were removed on day 18 of gestation and examined for external malformations, and the fore- and hindlimbs were examined by means of bone- and cartilage-stained cleared specimens. In +/+ x Pdn/+ matings, Pdn/+ fetuses, bearing preaxial polydactyly of the distal phalangeal type in the hindlimb and deformity of the 1st digit in the forelimb, were obtained in about 50% of the nontreated group. In treated fetuses, however, the incidence of polydactyly and deformity of the 1st digit decreased to 1.4 and 10.1%, respectively. Nontreated Pdn/Pdn fetuses exhibited preaxial polydactyly of the duplicated or triplicated metacarpal/metatarsal type both in the fore- and hindlimbs. In the treated Pdn/Pdn fetuses, the number of preaxial extra digits decreased in both limbs. Some hindlimbs of the treated Pdn/Pdn fetuses exhibited five metatarsals, normally. In the vitally stained specimens at 6 and 24 hours after injection of Ara-C, preaxial marginal necrotic zones (fMI) were observed in almost all of the treated embryos from +/+ x Pdn/+ matings. However, approximately half of the embryos did not exhibit fMI in the nontreated control group at the same stage. Those embryos deficient in fMI were regarded as Pdn/+. These findings indicated that a subteratogenic dose of Ara-C prevented the genetic expression of polydactyly in almost all Pdn/+ and some cases of Pdn/Pdn mice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Familial occurrence of unilateral biphalangeal duplication of the thumb.

Duplication of the thumb is not an uncommon condition and the biphalangeal type is considered to be a sporadic event. We report the familial occurrence of a unilateral thumb polydactyly type 4 of Wassel (12) or preaxial polydactyly type 1 of Temtamy (11).     

Are bowing of long tubular bones and preaxial polydactyly signs of the Meckel syndrome?

We describe four cases with signs resembling those of Meckel syndrome. Two cases demonstrated postaxial polydactyly; one case, preaxial polydactyly; and one case, pre- and postaxial polydactyly. Since there is at least one other reported case with preaxial polydactyly, it may be a rare sign of the Meckel syndrome. In all four cases, various degrees of bowing of the long tubular bones were observed. Since at least two cases exhibited typical Meckel syndrome and since in a few further reported cases X-ray examination revealed bowing of long tubular bones, this sign is considered to be a further, hitherto not well recognized sign of the Meckel syndrome, and not grounds for delineation of a new syndrome. An extensive review of the literature revealed, that shortened and bowed extremities may be present in about one-sixth of all cases with Meckel syndrome.     

Apert syndrome with partial preaxial polydactyly.

Acrocephalosyndactyly type I or Apert syndrome is characterized by craniosynostosis, particular dysmorphic features and abnormalities of the hands and feet. Rarely, polydactyly of the toes has been reported, and in this event the diagnosis of Carpenter syndrome must be discussed. A case of atypical Acrocephalosyndactyly type I syndrome with partial preaxial polydactyly is reported. Despite this preaxial polydactyly a diagnosis of Apert syndrome consecutive to a new mutation was made, and the possibility of recurrence considered to be highly improbable.     

Aberrant FGF signaling, independent of ectopic hedgehog signaling, initiates preaxial polydactyly in Dorking chickens

The formation of supernumerary digits, or polydactyly, is a common congenital malformation. Although mutations in a number of genes have been linked to polydactyly, the molecular etiology for a third of human disorders with polydactyly remains unknown. To increase our understanding of the potential causes for polydactyly, we characterized a spontaneous chicken mutant, known as Dorking. The hindlimbs of Dorkings form a preaxial supernumerary digit. During the early stages of limb development, ectopic expression of several genes, including Sonic Hedgehog (Shh) and Fibroblast Growth Factor 4 (Fgf4), was found in Dorking hindlimbs. In addition to ectopic gene expression, a decrease in cell death in the anterior of the developing Dorking hindlimb was observed. Further molecular investigation revealed that ectopic Fgf4 expression was initiated and maintained independent of ectopic Shh. Additionally, inhibition of Fgf signaling but not hedgehog signaling was capable of restoring the normal anterior domain of cell death in Dorking hindlimbs. Our data indicates that in Dorking chickens, preaxial polydactyly is initiated independent of Shh.     

Apert syndrome with preaxial polydactyly showing the typical mutation Ser252Trp in the FGFR2 gene

The Apert syndrome is characterized by craniosynostosis and syndactyly of hands and feet. Although most cases are sporadic, an autosomal dominant mode of inheritance is well documented. Two mutations in the FGFR2 gene (Ser252Trp and Pro253Arg) account for most of the cases. We report a patient with a rare form of Apert syndrome with polydactyly. The proposita has turribrachycephaly. complete syndactyly of 2nd to 5th digits ("mitten hands" and cutaneous fusion of all toes). The X-rays revealed craniosynostosis of the coronal suture and preaxial polydactyly of hands and feet with distal bony fusion. Molecular analysis found a C755G transversion (Ser252Trp) in the FGFR2 gene. Only eight patients with Apert syndrome and preaxial polydactyly have been reported and this is the first case in which molecular diagnosis is available. On the basis of the molecular findings in this patient, polydactyly should be considered part of the spectrum of abnormalities in the Apert syndrome. This assertion would establish the need for a new molecular classification of the acrocephalopolysyndactylies.     

Polydactyly lethal: a new mutant spontaneously occurring in the FPL strain of rats

A new mutant gene that causes preaxial polydactyly in the hindlimbs was found in the strain of rats with fused pulmonary lobes (fpl). Genetic analysis has revealed that the new mutation is inherited as an autosomal recessive trait and is not closely linked with the fpl gene. Since homozygous mutants die within the first 2 days after birth, the mutant gene was named polydactyly lethal, gene symbol pl. A test for allelism between the pl gene and another gene, pd, which also causes preaxial duplication anomalies, showed no allelism between these two genes. Skeletal examination revealed that all pl/pl newborns had thickening and/or bifurcation of tarsal I and metatarsal I, as well as duplication of the proximal and distal phalanges of digit I in the hindlimbs. In some cases, phalangeal duplication or bifurcation in digit I with thickening of metacarpal I was also found in the forelimbs, although extra forelimb digits were not detected externally. The pl/pl newborns showed hunchback-like abnormal posture externally and had several associated vertebral abnormalities in varying degrees, i.e., kyphosis, scoliosis, splitting of the thoracic vertebral bodies, and fusion of the lumbar vertebral bodies. No major malformations were seen in the visceral organs. The cause of neonatal deaths has not yet been determined.     

Genetical and epidemiological studies of polydactyly in Hungary

Polydactyly is one of the most frequently observed human congenital limb malformations. Sporadic cases of polydactyly have been described, but most show an autosomal dominant pattern of inheritance. The purpose of this study was to investigate the frequency of polydactyly among children born between 1980 and 1997 in Hungary. The predominance of the postaxial type over the preaxial one was less than expected. These malformations affected significantly more boys than girls. The proportion of children with low birth weight affected by polydactyly was higher than expected. Among mothers giving life to offspring with polydactyly, the prevalence was high in the older age group. We analysed the regional distribution in Hungary and the twin frequency in connection with polydactyly. From our results comparing it to the current literature data we made conclusions about the possible causes of the development of polydactyly.     

Case of bilateral preaxial polydactyly in a 7-week-old human embryo

In the translucent preparation, totally stained with alcian blue and alizarin red, bilateral preaxial polydactyly (an additional finger makes a joint with the I metacarpal bone anlage) and the epicondyle process on the brachial bone anlage have been revealed.     

Dysmorphology report: on the association of microcephaly and preaxial polydactyly. Another example of Howard-Young syndrome.

We present a 5-year-old boy with developmental delay, severe microcephaly and preaxial polydactyly. These features are very similar to those previously described by Howard and Young (1) in their princeps report.     

Anatomical features associated with preaxial duplication (pd): a recessive mutation in the rat

Preaxial polydactyly of the fore- and hindlimbs was found in Wistar-derived rats in 1978. Genetic analysis indicated that the polydactyly was due to the effects of an autosomal recessive gene (gene symbol; pd). Polydactylous homozygous rats had two or three pollices (six or seven digits) in the forelimbs and one to three preaxial extra digits (six to eight digits) in the hindlimbs. Skeletal examination revealed the presence of the extra carpal, metacarpal, and phalangeal bones that seemed to be complete or incomplete duplication of the navicular, greater multangular, first metacarpal, and phalanges of digit I in the forelimbs. In the hindlimbs, extra tarsal, metatarsal, and phalangeal bones were also observed preaxially. These extra elements seemed to be mirror-image duplications of the talus, navicular, second cuneiform, third cuneiform, cuboid, and metatarsals and phalanges of digits II-V with the absence of the first cuneiform, tibiale, first metatarsal, and phalanges of digit I. In addition, morphological changes were observed in the humerus, radius, and ulna in the forelimbs and femur, tibia, and fibula in the hindlimbs. Especially in the radius and tibia, thickening and bifurcation were found, indicating incomplete duplication of these bones. Based on these findings, the limb anomaly was classified as preaxial carpometacarpal/tarsometatarsal-type polydactyly with incomplete duplication of the radius and tibia. The mutant rats had other associated anomalies such as accessory spleens and cryptorchism. The males are sterile, whereas the females breed normally.     

Kaufmann syndrome or VACTERL association? Discussion of a differential diagnosis

The authors describe a dysmature female newborn, with multiple birth defects, who died soon after birth. At first polydactyly and hydrometrocolpos let think of a Kaufman syndrome, with autosomal recessive inheritance. But due to the presence of other malformations and since polydactyly is preaxial, the whole clinical and anatomical picture may be put into the frame of VACTERL association, mainly sporadic. Thus seemingly hydrometrocolpos and urogenital sinus have to be added, although rarely, to the other known defects of the VACTERL association.     

Review of drug-induced limb defects in mammals

The objective of this paper was to illustrate the spectrum of possible limb malformations in mammals resulting from drug exposure. A bibliography of 171 papers from 20 journals was generated from which pertinent data (drug used, limb defects reported, predominant defect location) were tabulated. These data should provide a basis for predictions about types of defects that might be expected in further studies and for judging postulated drug-induced human limb defects. However, direct extrapolation to humans is inappropriate. The following trends were observed: 1) Distal limb defects (autopod) are almost twice as common as proximal limb defects (stylopod and zygopod). 2) Ectrodactyly is the single most common type of limb defect, accounting for over half of the autopod defects. 3) Ectrodactyly is almost twice as common in the hindlimb as in the forelimb. 4) Postaxial ectrodactyly is over twice as common as preaxial ectrodactyly in the forelimb, but preaxial ectrodactyly is four times more common in the hindlimbs. 5) Polydactyly occurs with approximately equal frequency in forelimbs and hindlimbs, and preaxial polydactyly is most common in both fore and hindlimbs. 6) Polymelia (supernumerary limbs) occurred in one case, and may have been a spurious result. 7) Either transverse hemimelia is greatly underreported in teratology studies or it essentially does not occur. We have concluded that, at least in some cases, acetazolamide, adenine, 1,7-dimethylxanthine, and xanthine derivative aminophylline, retinoic acid, acetoxy-methyl-methylnitrosamine, aspirin, and cadmium can all cause unilateral defects.     

Polydactyly in the American Indian.

Polydactyly has an incidence in the American Indian twice that of Caucasians. A minimum estimate of this incidence is 2.40 per 1,000 live births. Preaxial type 1 has an incidence three to four times that reported for Caucasians or Negroes. The overall sex ratio in Indians is distorted with more males affected than females. The preaxial type 1 anomaly has a strong predilection for the hands and always is unilateral in contrast to postaxial type B where more than one-half are bilateral. The evidence to date, consisting of varying incidences of specific types of polydactyly among American whites, Negroes, and Indians in varying enviroments, suggests different gene-frequencies for polydactyly in each population. The incidence in Indians with 50% Caucasian admixture suggests that the factors controlling polydactyly are in large part genetically determined. Family studies and twin studies reported elsewhere offer no clear-cut genetic model which explains the highly variable gene frequencies.     

Acrocallosal syndrome in a child with de novo inverted tandem duplication of 12p11.2-p13.3.

Report on the child of normal unrelated parents presenting the typical features of acrocallosal syndrome (craniofacial dysmorphy, mental deficiency, convulsive disorder, agenesis of corpus callosum, preaxial polydactyly "hallux duplex" of both feet, and in addition diabetes insipidus) in which a mirror duplication of nearly the entire short arm of chromosome 12 was discovered. Since the symptomatology of trisomy and tetrasomy 12p shows some overlap with acrocallosal syndrome a common origin of the monogenic disorder and the chromosomal phenotypes is discussed.