Disease relevance of Syndactyly

• Apert syndrome is a distinctive human malformation comprising craniosynostosis and severe syndactyly of the hands and feet [1].
• The AER hyperplasia and its effect on early digital patterning distinguish sm from many other syndactylies that result from later failure of cell death in the interdigital areas [2].
• Apert syndrome, one of five craniosynostosis syndromes caused by allelic mutations of fibroblast growth-factor receptor 2 (FGFR2), is characterized by symmetrical bony syndactyly of the hands and feet [3].
• Saethre-Chotzen syndrome, a common autosomal dominant craniosynostosis in humans, is characterized by brachydactyly, soft tissue syndactyly and facial dysmorphism including ptosis, facial asymmetry, and prominent ear crura [4].
• Association of syndactyly, ectodermal dysplasia, and cleft lip and palate: report of two sibs from Turkey [5].

Psychiatry related information on Syndactyly

• His mother also has microcephaly, similar facial appearance, short fifth fingers with single flexion crease, syndactyly of toes 4-5, and learning disabilities [6].
• Apert syndrome, an autosomal dominant disorder characterized by craniosynostosis, mid-facial malformations, symmetric bony syndactyly of hands and feet, and varying degrees of mental retardation, is most frequently caused by a de novo mutation [7].

High impact information on Syndactyly

• Fraser syndrome is a recessive, multisystem disorder presenting with cryptophthalmos, syndactyly and renal defects and associated with loss-of-function mutations of the extracellular matrix protein FRAS1 [8].
• Here we describe how the loss of a cytoplasmic multi-PDZ scaffolding protein, glutamate receptor interacting protein 1 (GRIP1), leads to the formation of subepidermal hemorrhagic blisters, renal agenesis, syndactyly or polydactyly and permanent fusion of eyelids (cryptophthalmos) [9].
• Both PHS and GCPS have polysyndactyly, abnormal craniofacial features and are inherited in an autosomal dominant pattern, but they are clinically distinct [10].
• To elucidate the contribution of the extracellular microfibril-elastic fiber network to vertebrate organogenesis, we generated fibrillin 2 (Fbn2)-null mice by gene targeting and identified a limb-patterning defect in the form of bilateral syndactyly [11].
• They exhibit multiple developmental defects, including failure of anterior neural tube closure (exencephaly), failure of digit septation (syndactyly), and dysmorphogenesis of the placental labyrinth [12].

Chemical compound and disease context of Syndactyly

• In the course of performing an N-ethyl-N-nitrosourea mutagenesis screen, we identified a dominant mouse mutation that exhibits many classic symptoms of ODDD, including syndactyly, enamel hypoplasia, craniofacial anomalies and cardiac dysfunction [13].
• Together with the absence of anomalies of cholesterol metabolism, a combination of oral frenula, laryngeal malformations, digestive abnormalities, intercalary polysyndactyly, generalised brachytelephalangism, and nail hypoplasia should allow the delineation of Pallister-Hall syndrome, even when a CNS tumour is absent [14].
• We report on a male infant with an unusual type of acrocephalosyndactyly presenting with unilateral coronal craniosynostosis, cutaneous syndactyly of toes 2 and 3, loss of distal triradii, and transverse alignment of dermal ridges of the palm suggesting syndactyly, atresia of the proximal jejunum, and anal stenosis [15].
• Diphenylhydantoin produced a low incidence of syndactyly and oligodactyly [16].
• Polydactyly and polysyndactyly induced by prenatal exposure to ethanol [17].

Biological context of Syndactyly

• Craniosynostosis and syndactyly: expanding the 11q-- chromosomal deletion phenotype [18].
• Mice heterozygous for the Ft mutation are characterized by partial syndactyly of forelimbs and massive thymic hyperplasia indicating that programmed cell death is affected [19].
• The polydactyly may have been due to effects on mesenchymal cells producing localized cell proliferation, whereas syndactyly may have been due to effects on precartilage cells, resulting in excess migration of mesenchymal cells toward the digits, leaving the connective tissue at the interdigital space to develop inadequately [20].
• The human developmental disorder Syndactyly type 1 (SD1) maps to this region on chromosome 2 and the FU coding region was sequenced using genomic DNA from an affected individual in a linked family [21].

Anatomical context of Syndactyly

• Apert syndrome (AS) is characterized by craniosynostosis (premature fusion of cranial sutures) and severe syndactyly of the hands and feet [22].
• Gas1 mutant limbs have defects in the proliferation of the AER and the mesenchyme and develop with small autopods, missing phalanges and anterior digit syndactyly [23].
• doubleridge is a transgene-induced mutation characterized by polydactyly and syndactyly of the forelimbs [24].
• Animals heterozygous for the polydactyly ems (Pde) mutation display preaxial polydactyly of the hindlimbs, and homozygous syndactyly ems (sne) animals are characterized by a fusion of the middle digits of their hindlimbs and sometimes forelimbs [25].
• We report on 3 members of a Spanish family with partial aphalangia, syndactyly with duplication of metatarsal IV, microcephaly, dull intelligence, and short stature [26].

Gene context of Syndactyly

• In addition, a recently identified ligand-dependent S252L/A315S double mutation in FGFR2 was shown to cause syndactyly in the absence of craniosynostosis [27].
• In the current investigation, we have analysed the classical mouse mutant shaker-with-syndactylism using a positional candidate approach and demonstrated that loss-of-function mutations outside the "neonatal region" of Fbn2 cause syndactyly in mice [28].
• Localization of the syndactyly type II (synpolydactyly) locus to 2q31 region and identification of tight linkage to HOXD8 intragenic marker [29].
• Syndactyly of Ft/+ mice correlates with an imbalance in bmp4 and fgf8 expression [30].
• Boy with syndactylies, macrocephaly, and severe skeletal dysplasia: not a new syndrome, but two dominant mutations (GLI3 E543X and COL2A1 G973R) in the same individual [31].

Analytical, diagnostic and therapeutic context of Syndactyly

• He had a long broad nose with hypoplasia of the alae nasi, conductive hearing loss requiring hearing aids, muscular build, stiff spine, prominent acromia, pectus excavatum, ischial prominences, short fifth fingers, fusion at the proximal interphalangeal joints of the fifth fingers with indistinct overlying creases, and toe syndactyly [32].
• Intra-adnexal injections of glucose into the rabbit embryo have induced amputations of digits or segments of limbs, congenital grooves, amniotic bands, club feet, syndactyly, hare lip, anencephaly, and ulcerations of the scalp [33].

References