Expression of Fibroblast Growth Factor 4 in a Rat Model of Polydactyly of the Thumb Induced by Cytarabine.

BACKGROUND The aim of this study was to assess the expression and mechanisms of fibroblast growth factor 4 in polydactyly of the thumb induced by cytarabine. MATERIAL AND METHODS Rats were intraperitoneally injected with cytarabine at different gestation periods (12.5 days, 13.5 days, and 14.5 days) to establish a polydactyly of the thumb model. Then, the expression of FGF4 in polydactyly was studied by whole-mount in situ hybridization. We used hematoxylin & eosin stain and cartilage stain to investigate the development of the skeleton and tissues in the embryo. Pictures were taken to determine the general shape of the deformity, then X-rays were taken to detect bone distortion of the rats born with a congenital malformation. RESULTS In the experimental group (11.5 days, 12.5 days, 13.5 days, and 14.5 days), whole-mount in situ hybridization showed that the FGF4 expression at the tip of the embryonic limb bud was significantly increased compared with the control group and FGF4 was distributed in a wider range and lasted longer than in the control group (P<0.01). HE staining and cartilage staining showed that there was an extra metacarpal bone and a phalanx in the rats with polydactyly of the thumb (P<0.01). Images of the deformed limbs showed polydactyly and syndactyly of the thumb in the rats. Further X-ray examination revealed 1 extra metacarpal bone and 1 extra phalanx. CONCLUSIONS Cytarabine can induce polydactyly and syndactyly of the thumb in rats. In this process, cytarabine can induce the expression of FGF4 on the tip of the embryonic limb bud, which further leads to abnormal development of the embryonic limb bud and eventually causes a congenital deformity.

Review of the molecular development of the thumb: digit primera.

BACKGROUND: The thumb, or digit 1, is not a typical digit. In addition to its unusual mobility and function, its formation is also unusual. It is the last digit to form and the most commonly targeted when limb development is disrupted. The thumb domain is defined by the overlapping expression of HOXA13, TBX5, GLI3R, and HOXD13 and, importantly, by an absence of other distal HOXD transcription factors. This brief review, combining developmental biology and clinical genetics, discusses the current understanding of how the thumb domain is established.

Fanconi anemia with concurrent thumb polydactyly and dorsal dimelia: a case report with discussion of embryology.

Fanconi anemia is known to be associated with radial ray deficiency (thumb and radius hypoplasia), and its embryological basis remains to be poorly understood. We describe a rare case of Fanconi anemia with concurrent thumb polydactyly and dorsal dimelia. The embryological basis of limb abnormalities in Fanconi anemia patients is thought to be based on the complex interactions between the apical ectodermal ridge (where Fanconi anemia genes are expressed) and both the mesoderm (where Spalt-like 4 (SALL4) and Sonic hedgehog (SHH) are located and which are responsible for radial ray deficiency, thumb polydactyly, and triphalangism) and the dorsoventral axis (an error in that axis leads to dorsal dimelia).

Accessory head of flexor pollicis longus muscle in fetuses and adult cadavers and its relation to anterior interosseous nerve.

This study was conducted to examine the accessory head of flexor pollicis longus muscle (ahFPL) and its relation with the anterior interosseous nerve (AIN) in human fetuses and adult cadavers. Ninety fetus forearms and 52 adult cadaver forearms were dissected to evaluate the incidence, morphology, and innervation of the ahFPL. The ahFPL was observed in 29/90 (32%) of the fetus forearms and 20/52 (39%) of the adult cadaver forearms. The overall side incidence was 34.5% (49/142) among total forearms examined. On the other hand, the population incidence of ahFPL was 42% (19/45) in fetuses while it was 50% (12/24) in adult cadavers. So, the overall incidence in humans was 44.9% (31/69) in the population studied. Compression of the AIN in the forearm by the ahFPL is known as one of the causes of the anterior interosseous nerve syndrome (AINS). So, the relation of ahFPL with the AIN was evaluated, and in light of previous classifications a modified new classification is proposed. The most common relation detected in this study was Type IVa (71.4%) (AIN and its branches coursed posterior to the ahFPL). While Type I was not observed in this study, the incidences of Type II, Type III, and Type IVb (all AIN branches 'without AIN itself' coursed posterior to the ahFPL) were 2%, 14.3%, and 12.3%, respectively. The Types I, IVa, and IVb are thought to be associated with complete or incomplete types of AINS and Type III with incomplete type of AINS only.

Development of the deep flexor tendons and lumbricalis muscle in the hand and foot: a histological study using human mid-term foetuses.

To revisit foetal development of the deep flexor tendons of the hand and foot, we examined the paraffin-embedded histology of 20 mid-term foetuses at 8-15 weeks of estimated gestational age (35-118 mm crown-rump length or CRL). At 8-9 weeks, in front of the metacarpal bones, the flexor pollicis longus and flexor digitorum profundus (FDP) muscles provided a plate-like, common tendon from which the lumbricalis muscles originated. However, in the foot, we had no evidence of such a common tendon. The flexor pollicis tendon was separated from the common tendon at 9-10 weeks possibly due to mechanical stress from the laterally growing thumb. Notably, at the lumbricalis muscle origins at 10-12 weeks, the FDP and flexor digitorum longus tendons remained undifferentiated and the primitive tenocytes were dispersed from them. The dispersed cells seemed to develop into an interface tissue between the lumbricalis muscle fibre and the deep tendon. In 3 of 5 specimens at 15 weeks, we found an excess number of the FDP tendons (5-7) in the proximal side of the lumbricalis muscle origin. However, the excess tendons dispersed in the lumbricalis muscle origin. The development of the lumbricalis muscle origin might follow the tendon splitting for four fingers. However, conversely, we hypothesised that the developing lumbricalis muscles re-arranged the deep flexor tendons to provide a configuration of one deep tendon per one finger (or toe). The quadrates plantae muscle seemed not to contribute on the re-arrangement.

Pacinian Corpuscles in the Human Fetal Finger and Thumb: A Study Using 3D Reconstruction and Immunohistochemistry.

The detailed distribution of Pacinian corpuscles was evaluated by viewing the transverse sections of all fingers and thumbs, including the interdigital areas, from eight hands of five fetuses of gestational age 28-33 weeks (crown-rump length 230-290 mm). Among the 40 fingers and thumbs, serial sections were prepared for 3D reconstructions of nerve elements in the distal and middle phalangeal segments of three fifth fingers; in these three fingers, the distal segment contained 45-75 Pacinian corpuscles. These Pacinian corpuscles were 0.2-1.0 mm in length and 0.05-0.3 mm in thickness, oriented along the proximodistal axis and arranged along the palmar digital nerve branches. Other than beneath the digital skin, small corpuscles (<0.1 mm in thickness) were observed within the tendon sheath of the flexors in the middle or distal segment of five fetuses and in the nail beds of four fetuses. Clusters of 5-20 corpuscles formed bouquet- or tree-like arrangements along neurovascular bundles in the fingers, thumbs and interdigital areas. Because the space beneath the skin was thick and loose in the interdigital area, trees in the interdigital area were up to 2 mm long. Regardless of site, the central core of each corpuscle was positive for S100 protein, while the core and parts of the capillaries in the corpuscle were weakly positive for nestin. Because corpuscles in the tendon sheath and nail bed, as well as bouquet- and tree-like arrangements of corpuscles, have not been reported in adults, these morphologies are likely specific to fetuses. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 301:154-165, 2018. © 2017 Wiley Periodicals, Inc.

The hypoplastic thumb.

Thumb hypoplasia is part of a spectrum of radial longitudinal deficiencies involving the upper limb. Systemic involvement of other organ systems is not uncommon, thus requiring a team approach to management. Because of the variety of anatomic abnormalities associated with thumb hypoplasia, clinical and intraoperative evaluation of the thumb must be precise. Effective management of thumb hypoplasia requires an understanding of the embryology, epidemiology, classification, presentation, and management options. Management, which is primarily determined by the grade of thumb hypoplasia, may include nonsurgical techniques, reconstruction, pollicization, and, recently, microsurgical procedures.

The windblown hand - diagnosis, clinical picture and pathogenesis.

The syndrome of the windblown hand deformity is a complex constellation of malformations affecting not only the head and the feet but also the hands in a quite distinct manner. In the hand, it involves congenital bilateral flexion contracture with ulnar deviation of the metacarpophalangeal joints. The thumb is characteristically adducted (reaching the palm; "thumb-in-palm deformity") with flexion of the MP joint and hyperextension of the IP joint. The etiology is basically unknown. We present two theories based on knowledge derived from the disciplines of evolution biology and embryology. We believe that the atavistic appearance of phylogenetically primitive muscle groups in conjunction with an impaired rotation of the extremities during embryological development account for this malformation syndrome.

Embryological development and prevalence of thumb flexion creases.

A study of the embryological development and morphology of the thumb flexion creases is presented. We used 178 human fetuses, at 6-20 weeks of gestational age, and 225 normal adults, aged 19-81 years, to observe the morphology and the timing and location of the appearance of the flexion creases. Most creases, that is, the regular, extra, and oblique creases, were found to develop concurrently with the appearance of the fetal volar pads, apparently independently of the thumb flexion movements. Although the regular creases usually appear to be simple, single creases, they seem to be formed by the radial and ulnar lateral crease segments that develop inwards from each lateral side. Our observations also suggest that the oblique and extra creases on the proximal phalanx of the thumb should be considered as common or "regular" creases, rather than anomalies, because of their high frequency in fetuses and in normal healthy adults.

Upper-limb-cardiovascular syndrome. Two cases of Holt-Oram syndrome.

Two cases of Holt-Oram syndrome with an atrial septal defect and thumb deformities are reported. The embryological basis for the association between skeletal malformations particularly of the hand, and congenital heart disease, is discussed.

Triphalangeal thumb.

Triphalangeal thumb (TPT), a rare malformation of uncertain pathogenesis, may occur as an isolated defect, in association with other malformations of the hands, or as a feature of a syndrome or sequence. Isolated TPT occurs in two functional types: opposable and non-opposable. The latter appears to be inherited as a simple autosomal dominant trait, while the former is generally sporadic. TPT is associated with a number of specific malformations of the hand or foot, several of which have a well documented autosomal dominant pattern of inheritance. TPT is a feature of a number of specific syndromes. In this setting it may be associated with radial hypoplasia, bone marrow dysfunction, congenital heart disease, lung hypoplasia or agenesis, anorectal malformations, sensorineural hearing loss, onychodystrophy, mental retardation, and other disorders. TPT serves as a useful marker in such patients; in conjunction with the clinical and radiological findings, it can help to establish the correct diagnosis, leading to appropriate management and genetic counselling.

Experimental study on pathogenesis of polydactyly of the thumb.

The pathogenesis of polydactyly of the thumb was investigated by administration of single dose of cytosine arabinoside (ara-C, 100 mg/kg) to pregnant SD rats on day 11. Marked growth discrepancy between ectoderm and mesoderm of the limb bud was observed both morphologically and biochemically 24 hours after treatment. The growth discrepancy was induced by interference with proliferation process of mesodermal cells. The different susceptibility of ectodermal cells and mesodermal cells to the teratogenic agent was found to depend on the stage difference of cellular differentiation of each tissue. Cephalocaudal asymmetry of the limb bud, as well as relative overgrowth of ectodermal tissue, was postulated to be the cause of protrusion of the preaxial border of the limb bud, which was an initial sign of extra first digit formation.