Atypical malformations in an infant exposed to warfarin during the first trimester of pregnancy

We report a dysmorphic female infant whose mother took warfarin in therapeutic doses during the first 6 weeks of pregnancy. At birth the infant was small for dates and had a triangular facial appearance, micrognathia, microglossia, short fingers and toes, and hypoplastic nails. A skeletal survey revealed hypoplastic distal phalanges in the fingers and toes; there was no epiphyseal stippling. The pattern of malformations present in this infant may either represent the earliest teratogenic effects of warfarin or the fortuitous association of exposure to warfarin and unexplained dysmorphic features.     

Pedal symphalangism in modern American and Japanese skeletons

Pedal symphalangism is a surprisingly common heritable trait of the human foot. In individuals exhibiting the trait, the joint between the intermediate and distal phalanges of one or more lateral toes never develops, resulting in toes with two phalanges rather than three. This study was undertaken to explore variation in the frequency of pedal symphalangism among groups with widely different geographic ancestry, and to consider the applicability of this trait to skeletal biological distance studies. A total of 460 Euro-American, 191 African-American and 99 Japanese skeletons were examined for presence of pedal symphalangism. The American individuals date to the first half of the 20th c, while the Japanese individuals date to the late 19th and early 20th c. Although the country of ancestry is unknown for most of the American individuals, the Euro-Americans appear to be largely northern European, with roots in Germany, Ireland and Scandinavia, while the African-Americans are primarily descendants of slaves with roots in west African countries such as Nigeria, Benin, Togo, Ghana and Sierra Leone. Frequencies of fifth toe pedal symphalangism were calculated and compared among all three samples and found to be significantly higher in modern Japanese (83.7%) than in either Euro-Americans (46.4%) or African-Americans (44.0%). The Euro- and African-American frequencies were statistically indistinguishable for symphalangism of the fifth toe. In the fourth toe, however, the opposite result was found. The African-American frequency (7.9%) was significantly higher than the Euro-American frequency (2.6%), while no difference was found between the African-Americans and Japanese (11.7%). Since fourth toe pedal symphalangism has never been observed in the absence of fifth toe involvement, some of the same genes are clearly involved in producing the trait in both toes. However, differences in the pattern of fourth and fifth toe expression among the three groups identified in this study suggest that additional genetic or developmental factors may play a role in expression of pedal symphalangism in each of the toes.     

Brachydactylia with symphalangism,probably autosomal recessive

Summary Association, in one patient, of the following malformations: brachydactylia of all segments but terminal phalanges; proximal symphalangism of many fingers and toes; abnormalities of carpal and tarsal bones; partial duplication of both big toes; mild hypertelorism. Genetic transmission seems to be recessive autosomal.     

Minimizing impairment in laborers with finger losses distal to the proximal interphalangeal joint by second toe transfer

Traditionally, toe-to-hand transfers have been reserved for thumb amputations or for use after severe mutilating injuries. The authors report their experience with the use of second toe-for-finger amputations with preserved or reconstructible proximal interphalangeal joints in manual workers. The aim of the procedure was to reduce impairment and to upgrade the hand from a functional and cosmetic standpoint. Fifteen second-toe wrap-around or variations were carried out on 11 adults (18 to 41 years old). Four patients with two or more finger amputations received two sequential second toes; four patients with two finger amputations received one toe; and each of three patients with single-digit amputation received a single toe. All but one amputation were performed less than 3 weeks after the accident. All toes survived. Range of motion at the native proximal interphalangeal joint was more than 90 percent in all patients but one; however, it was minimal at the transplanted joints. Patient satisfaction was high from a cosmetic and functional standpoint. Ten of 11 laborers resumed their previous activity. On the basis of this experience, a classification with aesthetic and functional implications is proposed to help in the decision-making process when dealing with multidigital injuries. It is concluded that second-toe transfer is an excellent choice for finger amputation distal to the proximal interphalangeal joint in laborers. Its prime indication is for amputations of two fingers where at least one toe should be transferred, as required, to achieve an "acceptable hand" (three-fingered hand). Early transfer allows salvage of critical structures from the damaged finger, such as joints, tendons, and bone, that otherwise would be lost. Early transplantation is highly recommended.     

Familial symphalangism syndrome transmitted through five generations.

We report on proximal symphalangism of the four last fingers, transmitted through five generations of an African family. Intrafamilial variations of the disorder are due to the heterogeneity of associated anomalies. This familial trait resembles multiple synostosis disease, however, it is not restricted to synostoses and appears to be more generalised. To our knowledge this is the first report of a familial trait associating proximal and distal symphalangism. The distribution of elementary anomalies in this family suggests a link in their pathogeny and raises the question of embryological equivalence for some of them. Symphalangism seems to be a symptom of a more generalised disorder, the comprehension of which requires a better coordination of clinical, embryological and genetic data.     

Symphalangismus,Strabismus und Mittelohrmißbildung

Zusammenfassung Es wird über die Kombination von Symphalangismus und Mittelohrmißbildung innerhalb einer Familie berichtet. Für die Skeletfehlentwicklung und für die Mittelohrmißbildung wird der gleiche Gendefekt verantwortlich gemacht. Der kongenitale Strabismus bei den Geschwistern kann nicht sicher zu den anderen beiden Mißbildungen in Beziehung gebracht werden. Der genetische Zusammenhang einer erstmals bei Symphalangismus beschriebenen Spina bifida mit den Finger- und Zehenmißbildungen wird abgelehnt.

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Symphalangism, strabism, and anomaly of the middle ear

Summary This report describes a combination of symphalangism and anomaly of the middle ear in a family. The same genetic defect is thought to be responsible for both the deformation of the skeleton and the anomaly of the middle ear. The authors are not sure whether there is any connection between the congenital strabismus and the two other anomalies of brother and sister. The assumption of a genetic connection between spina bifida, which was described for the first time with symphalangism, and the anomalies of the fingers and toes is rejected.

     

Power comparisons of the transmission/disequilibrium test and sib-transmission/disequilibrium-test statistics.

Brachydactyly type B (BDB), an autosomal dominant disorder, is the most severe of the brachydactylies and is characterized by hypoplasia or absence of the terminal portions of the index to little fingers, usually with absence of the nails. The thumbs may be of normal length but are often flattened and occasionally are bifid. The feet are similarly but less severely affected. We have performed a genomewide linkage analysis of three families with BDB, two English and one Portugese. The two English families show linkage to the same region on chromosome 9 (combined multipoint maximum LOD score 8.69 with marker D9S257). The 16-cM disease interval is defined by recombinations with markers D9S1680 and D9S1786. These two families share an identical disease haplotype over 18 markers, inclusive of D9S278-D9S280. This provides strong evidence that the English families have the same ancestral mutation, which reduces the disease interval to <12.7 cM between markers D9S257 and D9S1851 in chromosome band 9q22. In the Portuguese family, we excluded linkage to this region, a result indicating that BDB is genetically heterogeneous. Reflecting this, there were atypical clinical features in this family, with shortening of the thumbs and absence or hypoplasia of the nails of the thumb and hallux. These results enable a refined classification of BDB and identify a novel locus for digit morphogenesis in 9q22.     

Autosomal dominant stapes ankylosis with broad thumbs and toes,hyperopia, and skeletal anomalies is caused by heterozygous nonsense and frameshift mutations in NOG,the gene encoding noggin

Although fixation of the stapes is usually progressive and secondary to otosclerosis, it may present congenitally, with other skeletal manifestations, as an autosomal dominant syndrome-such as proximal symphalangism (SYM1) or multiple-synostoses syndrome (SYNS1), both of which are caused by mutations in NOG, the gene encoding noggin. We describe a family that was ascertained to have nonsyndromic otosclerosis but was subsequently found to have a congenital stapes ankylosis syndrome that included hyperopia, a hemicylindrical nose, broad thumbs and great toes, and other minor skeletal anomalies but lacked symphalangism. A heterozygous nonsense NOG mutation-c.328C-->T (Q110X), predicted to truncate the latter half of the protein-was identified, and a heterozygous insertion in NOG-c.252-253insC, in which the frameshift is predicted to result in 96 novel amino acids before premature truncation-was identified in a previously described second family with a similar phenotype. In contrast to most NOG mutations that have been reported in kindreds with SYM1 and SYNS1, the mutations observed in these families with stapes ankylosis without symphalangism are predicted to disrupt the cysteine-rich C-terminal domain. These clinical and molecular findings suggest that (1) a broader range of conductive hearing-loss phenotypes are associated with NOG mutations than had previously been recognized, (2) patients with sporadic or familial nonsyndromic otosclerosis should be evaluated for mild features of this syndrome, and (3) NOG alterations should be considered in conductive hearing loss with subtle clinical and skeletal features, even in the absence of symphalangism.     

Relative lengths of fingers and toes in human males and females

Digital scans of the hands and feet were obtained from 62 heterosexual females and 60 heterosexual males. Scans only of the hands were obtained from 29 homosexual females and 35 homosexual males. The lengths of the individual fingers and toes were estimated from those images by two experienced judges, and length ratios were constructed for all possible pairs of fingers (or toes) on each hand (or foot). Thumbs were not measured, but the great toe was measured and used to construct length ratios. Past research had concentrated on the relative lengths of the index and ring fingers (the 2D:4D ratio). This ratio is close to 1.0 in females and smaller than 1.0 in males. Here 2D:4D did exhibit the largest sex difference, for both hands, followed by 2D:5D and 3D:4D. The sex differences were larger for the right hand than for the left. For both homosexual females and homosexual males, nearly all of the length ratios for fingers were intermediate to those for heterosexual females and heterosexual males; that is, the ratios of homosexual females were masculinized and those of homosexual males were hypomasculinized, but few of these differences were significant. Because many toes were substantially arched, acceptable estimates of length often could not be obtained from the two-dimensional scans, meaning that conclusions about toes are much less certain than those for fingers. Nevertheless, the length ratios were generally larger for toes than for fingers, and the sex differences were generally smaller for toes.     

Aplasia of tibia with split-hand/split-foot deformity. Report of six families with 35 cases and consideration about variability and penetrance

Summary Six families with a total of 34 affected persons with the syndrome of tibial aplasia and ectrodactyly are reported. The spectrum of malformations is compared to that of 99 familial cases from the literature. The full-blown syndrome consists of bilateral aplasia of tibiae and split-hand/split-foot deformity. Additional malformations may be distal hypoplasia or bifurcation of femora, hypo- or aplasia of ulnae, and minor anomalies such as aplasia of patellae, hypoplastic big toes, postaxial and intermediate polydactyly in connection with split-hand deformity, and cup-shaped ears. The mildest visible manifestation may be hypoplastic big toes, the severest is tetramonodactyly or transverse hemimelia. This disorder is autosomal dominantly inherited. The penetrance is markedly reduced.     

Scoliosis, blindness and arachnodactyly in a large Turkish family: is it a new syndrome?

In this report we have described an affected sib in a large Turkish family who appears to have a new distinct dominantly-inherited blindness, scoliosis and arachnodactyly syndrome. The combination of clinical abnormalities in these patients did not initially suggest Marfan syndrome or other connective tissue disorders associated with ectopia lentis. The proband was a 16-year-old boy who was referred to our clinics for scoliosis. He had arachnodactyly of both fingers and toes. He had been suffering from progressive visual loss and strabismus since he was eight-years-old. His 20-year-old brother had severe kyphoscoliosis, and arachnodactyly of fingers and toes. He was 130 cm tall and was bilaterally blind. His 23-year-old sister had only eye findings but no arachnodactyly or scoliosis. His 60-year-old father had mild scoliosis, blindness and arachnodactyly and mother was normal. We performed routine mutation analyses in the genes FBN1, TGFBR1 and TGFBR2, but no mutation has been detected. Our Turkish patients are most likely affected by a hitherto unrecorded condition which is caused by an autosomal dominant gene defect with variable expression but we can not exclude multigenic inheritance. Further studies are needed to assess the contribution of sex influence to the syndrome because the female relative is less affected.     

A family study of dermatoglyphic traits in India. Resolution of genetic and environmental effects for manus,pes and total pattern ridge counts in man

Various constructed ridge count phenotypes were studied in two endogamous populations from peninsular India. Heritabilities were estimated for five summed pattern ridge count traits: fingers and toes together; palms and soles together; fingers and palms together (manus); toes and soles together (pes); and fingers, palms, toes and soles together, defined as the total ridge count in man. In general, these phenotypes were found to he highly heritable, with the summed ridge counts for fingers and toes, and total ridge count showing almost Complete determination by additive polygenes. Total manus and pes pattern counts are less heritable. Little or no uterine environmental effects were detected for any of these phenotypes.     

Ultrasonography,magnetic resonance imaging,radiography, and clinical assessment of inflammatory and destructive changes in fingers and toes of patients with psoriatic arthritis

The aim of the present study was to assess ultrasonography (US) for the detection of inflammatory and destructive changes in finger and toe joints, tendons, and entheses in patients with psoriasis-associated arthritis (PsA) by comparison with magnetic resonance imaging (MRI), projection radiography (x-ray), and clinical findings. Fifteen patients with PsA, 5 with rheumatoid arthritis (RA), and 5 healthy control persons were examined by means of US, contrast-enhanced MRI, x-ray, and clinical assessment. Each joint of the 2nd–5th finger (metacarpophalangeal joints, proximal interphalangeal [PIP] joints, and distal interphalangeal [DIP] joints) and 1st–5th metatarsophalangeal joints of both hands and feet were assessed with US for the presence of synovitis, bone erosions, bone proliferations, and capsular/extracapsular power Doppler signal (only in the PIP joints). The 2nd–5th flexor and extensor tendons of the fingers were assessed for the presence of insertional changes and tenosynovitis. One hand was assessed by means of MRI for the aforementioned changes. X-rays of both hands and feet were assessed for bone erosions and proliferations. US was repeated in 8 persons by another ultrasonographer. US and MRI were more sensitive to inflammatory and destructive changes than x-ray and clinical examination, and US showed a good interobserver agreement for bone changes (median 96% absolute agreement) and lower interobserver agreement for inflammatory changes (median 92% absolute agreement). A high absolute agreement (85% to 100%) for all destructive changes and a more moderate absolute agreement (73% to 100%) for the inflammatory pathologies were found between US and MRI. US detected a higher frequency of DIP joint changes in the PsA patients compared with RA patients. In particular, bone changes were found exclusively in PsA DIP joints. Furthermore, bone proliferations were more common and tenosynovitis was less frequent in PsA than RA. For other pathologies, no disease-specific pattern was observed. US and MRI have major potential for improved examination of joints, tendons, and entheses in fingers and toes of patients with PsA.     

Possible trisomy 1q25→1q32 in a malformed girl with a de novo insertion in 1q

Summary A newborn female is described who exhibited a characteristic facial dysmorphology including deep-set eyes, broad nasal bridge, small mouth, higharched and narrow palate, severely receding mandible and misshapen ears; constant flexion of the proximal interphalangeal joints, and short distal phalanges and nails of fingers; a congenital heart defect; marked muscular hypotonia, motor and growth retardation. She died at 4 months of age. Her karyotype revealed an additional band in 1q. Banding patterns and clinical picture suggest duplication of the segment 1q251q32.     

Clinical and molecular studies in two families with Fraser syndrome: a new FRAS1 gene mutation, prenatal ultrasound findings and implications for genetic counselling

Fraser syndrome is a rare autosomal recessive genetic disorder characterized by cryptophthalmus, variable expression of cutaneous syndactyly of fingers and toes, genital ambiguity and renal agenesis/dysgenesis. We present here molecular and clinical findings of four fetuses with FS from two families. Molecular genetic studies in the two families revealed mutations in FRAS1 gene allowing better genetic counselling and subsequent prenatal diagnosis in one of the two families. In family one, a nonsense mutation (c.3730C>T, p.R1244X) previously described in a Polish patient was found. In family two a novel nonsense mutation previously not known was detected (c.370C>T, p.R124X). PGD is planned for family 1.     

A simple method for characterising syndactyly in clinical practice

Non-syndromic syndactyly is a heterogeneous group of limb malformations involving webbing of fingers and/or toes. There are at least nine non-syndromic types described in the literature. For the clinician and the genetic counsellor not having gathered experience with this malformation, it is rather tedious to identify the correct subtype for the patient's phenotype. We therefore present a protocol for clinical use, which visualises the malformation in a graphical way and thereby simplifies typing. In addition, this protocol provides a simple documentation system for reporting clinical data for new syndactyly families. It might encourage clinicians to report families that are still unclassifed and thus, helping to extend and improve the existing classification system.     

Quantitative trace element analysis of human nails with external beam PIXE

External beam PIXE (Particle Induced X-ray Emission) analysis with a proton beam of 2.4 MeV was used to study trace element concentrations in human nails. The suitability of PIXE analysis regarding nail samples without any pretreatment besides washing was investigated. The main emphasis has been on the ability to obtain absolute concentration values and a new accurate method for nail sample standardization has been developed. Concentration values for the elements Ca, Cr, Mn, Fe, Ni, Cu, Zn, Se, Br, and Pb were determined from human nail samples. A comparison was made with nail samples taken from different fingers and toes to monitor intraindividual variation, and nails of different healthy individuals to get a view of the interindividual differences. The concentrations were also measured in relation to time in order to observe any possible short-term changes. The results are compared with the previous studies reported in the literature. The nail analysis is also compared to hair analysis in terms of detection limits, number of elements determinable, and standardization of the results.     

Effects on toes from prenatal exposure to anticonvulsants

BACKGROUND: Changes in the distal phalanges of the fingers, including coned epiphyses and hypoplasia of the phalanges, are recognized teratogenic effects of the anticonvulsant drugs phenytoin and phenobarbital. We hypothesized that the frequency of these changes would also be increased in the toes of children exposed to these drugs in comparison to unexposed children. METHODS: We report on the findings in an analysis of radiographs of the feet of 63 children exposed in utero to either phenytoin alone, phenobarbital alone or both drugs and 56 unexposed comparison children. RESULTS: Only subtle changes were identified. The frequency of coned epiphyses and hypoplasia of phalanges of the toes was the same in both the anticonvulsant and unexposed children. Among the anticonvulsant-exposed children, however, there was a strong association between the presence of coned epiphyses in the feet and in the hands: all five children with coned epiphyses in the hands, as described previously in the same individuals by Lu et al. ([2000] Teratology 61:277-283) had coned epiphyses in their feet (P = 0.0012). Measurements showed a shortening of metatarsals in all three treatment groups, but this was significant only in the phenytoin monotherapy-exposed children. CONCLUSIONS: Subtle changes are present in the phalanges and metatarsals of the feet of anticonvulsant-exposed children, but the overall frequency is much less than occurred in the hands of the same children. We conclude that the presence of either coned epiphyses or hypoplasia of the phalanges of the toes cannot be considered a distinctive feature of the teratogenicity of the anticonvulsant drugs phenytoin and phenobarbital.     

Toe and plantar dermatoglyphics in adult American Caucasians

The scarcity of information on control data of toe and plantar dermatoglyphics led us to undertake this study of adult American Caucasians. Toe and sole prints of 168 male and 83 female participants of the Baltimore Longitudinal Study of Aging were analyzed. Toe pattern frequencies demonstrate that fibular loops are the most prevalent pattern on the toes in both males and females. Pattern distribution by digit shows that arches are most often located on the fifth toe while whorls are found with greatest frequency on the third toe. Plantar pattern frequencies indicate that the most common pattern found in the hallucal area is the distal loop. Open fields are frequently found in the II and IV interdigital areas while distal loops are prevalent in the III area. These results are compared to the finger and palmar patterns of the same individuals. The distribution of patterns on the toes and fingers of the same individuals appear to be quite different. Population comparisons did not demonstrate a clear racial difference in the toe pattern frequencies or in the plantar areas.     

Entrapment of adult fingers between window glass and seal entry of a motor vehicle side door: an experimental study for investigation of the force at the subjective pain threshold

In modern motor vehicles with automatic power windows, a potential hazard exists for jam events of fingers between the window glass and seal entry. This study determined entrapment forces acting on adult fingers at the subjective maximum pain threshold during entrapment in such windows. The length and the girth of the proximal and distal interphalangeal joints of the triphalangeal fingers of the right hands of 109 participants (60 men, 49 women) were measured; the diameter was calculated from girth, which was assumed to be circular. The automatic power window system of a motor vehicle side door was changed to a mechanical system. During entrapment the force distributed across the four proximal interphalangeal joints (PIPs), and separately on the proximal interphalangeal (iPIP) and then the distal interphalangeal (iDIP) joints of the index finger was measured using a customized force sensor. The maximum bearable entrapment force was 97.2 ± 51.8 N for the PIPs, 43.4 ± 19.9 N for the iPIP, and 36.9 ± 17.8 N for the iDIP. The positive correlation between finger diameter and maximum entrapment force was significant. Particularly with regard to the risk to children's fingers, the 100 N statutory boundary value for closing force of electronic power windows should be reduced.