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Holt-Oram syndrome (HOS) is a rare disorder characterized by cardiac and upper-limb defects. Pathogenic variants in TBX5-a gene encoding a transcription factor important for heart and skeletal development-are the only known cause of HOS. Here, we present the identification and functional analysis of two novel TBX5 pathogenic variants found in two individuals with HOS presenting distinct phenotypes. The individual with the c.905delA variant has a severe cardiac phenotype but mild skeletal defects, unlike the individual with the c.246_249delGATG variant who has no cardiac problems but severe upper limbs malformations, including phocomelia. Both frameshift variants, c.246_249delGATG and c.905delA, generate mRNAs harbouring premature stop codons which, if not degraded by nonsense mediated decay, will lead to the production of shorter TBX5 proteins, p.Gln302Argfs*92 and p.Met83Phefs*6, respectively. Immunocytochemistry results suggest that both mutated proteins are produced and furthermore, like the wild-type protein, p.Gln302Argfs*92 mutant appears to be mainly localized in the nucleus, in contrast with p.Met83Phefs*6 mutant that displays a higher level of cytoplasmic localization. In addition, luciferase activity analysis revealed that none of the TBX5 mutants are capable of transactivating the NPPA promoter. In conclusion, our results provide evidence that both pathogenic variants cause a severe TBX5 loss-of-function, dramatically reducing its biological activity. The absence of cardiac problems in the individual with the p.Met83Phefs*6 variant supports the existence of other mechanisms/genes underlying the pathogenesis of HOS and/or the existence of an age-related delay in the development of a more serious cardiac phenotype. Further studies are required to understand the differential effects observed in the phenotypes of both individuals. Foundation for Science and Technology (FCT)Portuguese Foundation for Science and TechnologyEuropean Commission [UIDB/04326/2020]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BD/141918/2018, SFRH/BD/144230/2019]

Many research initiatives have been employed in upper limb prosthetics (ULP) in the last few decades. The body of knowledge is growing and inspired by new and interesting technology that has been brought to the market to facilitate functioning of people with upper limb defects. However, a lot of research initiatives do not reach the target population. Several reasons can be identified as to why research does not move beyond the lab, such as lack of research quality, disappointing results of new initiatives, lack of funding to further develop promising initiatives, and poor implementation or dissemination of results. In this paper, we will appraise the current status of the research in ULP. Furthermore, we will try to provide food for thought to scale up research in ULP, focusing on (1) translation of research findings, (2) the quality of innovations in the light of evidence-based medicine and evidence-based practice, (3) patient involvement, and (4) spreading of research findings by focusing on implementation and dissemination of results and collaboration in a national and international perspective. With this paper, we aim to open the discussion on scaling up research in the community of professionals working in the field of ULP.

Objective A very few flaps would be described as versatile as the Keystone Flap. There is an increasing demand for coverage of defects in lower limb due to traumatic defects as well as other parts of the body. Keystone flap is one of its kind, which is simple and easy to perform. It is a safe option for conditions where microsurgery may not be a viable option. The relative simplicity of this flap makes it a to go option at many places. Methods A prospective study was developed from October 2017 to December 2019 at SMS Hospital, Jaipur. We assessed the size of the flap, operation time, average hospital stay and the complications. Perforators over the leg were Doppler marked preoperatively over which the flap was raised. Results 50 patients were taken into the study. 30 key stone flaps were done to cover lower limb defects, 10 flaps were done for upper limb defects and the remaining 10 were for trunk defects. The average intraoperative time from skin incision to final suture was 50 min (range 20–90 min). The largest defect covered by keystone flap in our series measured 50 × 20 cm and the smallest defect covered was 8 × 4 cm. The average hospital stay was 3 days. We observed partial flap necrosis in 2 cases which required skin grafting. 3 other cases had wound infection leading to wound dehiscence, which required secondary suturing. The overall success rate was 95%. Conclusion The Keystone flap being a versatile flap with its qualities of replacing “like with like”, easy to perform, use of local tissue, good vascularity and a low complication rate makes it an excellent flap for a variety of defects. The KeyStone flap allows reconstruction in a single stage and is a relatively easy and fast technique for the beginner as well as the experienced surgeon. We believe it should be incorporated more into a surgeons practice.

Background. Evaluation of the result of functional prosthetics in patients with different upper limb defects is a topical problem of modern prosthetics. Providing patients with non-functional hand stumps with functional prostheses is not wide-scale and refers to atypical and experimental prosthetics. While new functional prosthetic hands appear, there is no algorithm for evaluating the results of prosthetics. Aim. This study aimed to evaluate the result of functional prosthetics in children with congenital defects of the hand and fingers by active prostheses. Materials and methods. We observed 67 children with congenital hand defects, of which 22 were included in the experimental prosthetics group. Bench test station was used for an objective assessment of the residual function of the hand. The booth imitated the tasks of an international competition for the users of Cybathlon rehabilitation equipment and allowed users to perform a series of tests, for each of which a certain number of evaluation points were awarded. Samples at the stand were supplemented with a subjective assessment of the function of the hand using the DASH questionnaire validated in Russia. Results. The best subjective assessment of the supply of an active prosthetic hand was determined in the patients with underdeveloped hand similar to the truncation of the hand proximal to the metacarpophalangeal joints. The lowest functionality score of the active prosthetic hand was obtained in cases of ectrodactyly and hypoplasia of 1–5 fingers, which was associated with a high residual functionality of the hand. Conclusions. In addition to training functions, the developed bench test station serves a diagnostic function as it evaluates the results of functional prosthetics in patients with upper limb defects in different levels, including defects on the hand and fingers. The results of the study on the station correlate with the results of the DASH questionnaire.

Background and Aims: To evaluate hospital care of children with congenital upper limb defects. Materials and Methods: Three hundred and sixty-two children with an upper limb defect, born 1993–2005, and alive after birth admission were identified in the Finnish Register of Congenital Malformations. The data on hospital care, with focus on operative treatment, were collected from the National Hospital Discharge Register, until 31 December 2009. Mean follow-up was 10.2 years (range: 4–17 years). The results were compared with data on the whole children population (1.1 million) in Finland. Results: Most children (321, 87%) with upper limb defects had hospital admissions: on average, one admission/year (range: 0–36), and they were treated in hospital 5 days/year (range: 0–150), which is 11-fold compared with an average child in Finland. Four surgical procedures/child were done (range: 0–45), including one hand surgical procedure. The most common procedures were orthopedic (513); gastrointestinal (263); ear, nose, and throat (143); dental (118); thoracic (48); and urologic (44). Of the 513 orthopedic procedures, 326 were directed to upper limbs, 107 to the lower limbs, and 10 to the spine. Median operation age was 2 years 7 months. Altogether, 60% of hospital admissions were non-surgical. Leading causes of non-operative hospital admissions were congenital anomalies (32%), gastroenterological problems (20%), respiratory tract conditions (13%), neurological problems (7%), perinatal conditions (5%), and infectious diseases (5%). Conclusion: Treatment of children with upper limb defects is teamwork between pediatric and surgical subspecialties. Burden of hospital care is 11-fold as compared with an average child.

AIMS: To evaluate the effects of pre-gestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM) on macrosomia and birth defects. METHODS: Existing birth registry data from the Perinatal Data System in Upstate New York was analysed. 650,914 women with a singleton term pregnancy (≥37 weeks) aged 18–55 years from 2004 to 2016 were included. RESULTS: The prevalence of macrosomia in infants born to women with PGDM and GDM were 26.0% and 16.4%, respectively, higher than that in the controls (11.2%). Compared with the controls (0.8%), the PGDM and GDM groups had higher prevalence of any birth defect (1.8% and 1.0%). The PGDM group had the highest prevalence of cyanotic heart disease (0.6%). Moreover, the PGDM group had higher prevalence of cleft lip and palate, cleft palate alone, hypospadias and limb reduction defect compared to the GDM and control groups (p < 0.05). However, these birth defects in the GDM group were similar to those in the controls. Both the PGDM and GDM groups had significantly elevated odds of macrosomia, cyanotic heart disease and any birth defect than controls. The PGDM group had higher odds of cleft lip and palate, cleft palate alone, hypospadias and limb reduction defect. CONCLUSIONS: Using the Perinatal Data System database, PGDM and GDM, especially PGDM, was associated with higher prevalence of macrosomia, cyanotic heart disease and any birth defect in singleton term pregnancy in Upstate New York. PGDM, not GDM had higher prevalence of cleft lip and palate, cleft palate alone, hypospadias and limb reduction defect.

Ichthyosis is a genetically and phenotypically heterogeneous disease that can be isolated and restricted to the skin manifestations or associated with extracutaneous symptoms. One of which is limb reduction defect known as CHILD syndrome; a rare inborn error of metabolism of cholesterol biosynthesis that is usually restricted to one side of the body. Here we describe an Egyptian child with generalized lamellar ichthyosis and limb reduction defect. Most probably this is a simple association and not a rare case of CHILD syndrome with bilateral skin involvement. Keywords: Ichthyosis; Limb reduction; CHILD; Autosomal recessive

BACKGROUND Reconstruction of the complex upper extremity defects is a challenging procedure for reconstructive surgeons because of the complex anatomical and functional structure of this region. In reconstruction, local and regional flap options involving the composite tissues are restricted. The posterior interosseous flap (PIO) has been presented 'in a single study' with a wide variety of uses, and in this study, the versatility of PIO has been tried to be emphasized by its multitude uses as well as its chance at adaptability to each case. Hence, due to this, the objective to highlight the versatile utility of the PIO flap in clinical practice and to present a good option for the reconstruction of complex upper limb defects for various cases have been targeted. METHODS We used 26 PIO flaps in 25 patients (18 male and seven female patients) with upper limb defects. The main etiological causes were burn contracture, traffic accident, firearm and acute burn injury. Twenty-two flaps were harvested as fasciocutaneous and four flaps as osteo-fasciocutaneous manner, which were applied to the metacarpal defects. In this study, 25 flaps were transferred as pedicled flaps, of which 23 and 2 flaps had reverse and antegrade blood flows, respectively, whereas one flap was used as a free flap. RESULTS The mean follow-up period was 14 months. All flaps except one, which had partial necrosis and secondary healed, survived completely. All patients were able to gain basic functions for daily routine activities in the late postoperative period. Patients and/or their parents were satisfied with the postoperative functional and aesthetic improvements. CONCLUSION Many advantages of the PIO flap make it useful for the reconstruction of upper limb complex defects. It can be versatilely used based on changing its flow direction and enrichment of contents.

Poland syndrome is a rare congenital disorder characterized by agenesis of the pectoralis major muscle. It is generally unilateral, right-sided, and can be associated with a myriad of thoracic and upper limb defects. Knowledge of this disorder can lead the astute clinician to prompt diagnosis and referral to surgical specialists for further workup. Surgery is often performed for either esthetic or functional concerns.

Цель. Разработать технологию изготовления индивидуальной полноконтактной приемной гильзы протезов предплечья. Материалы и методы. Разработана и апробирована новая технология изготовления индивидуальной полноконтактной приемной гильзы протезов предплечья, включающая этап выполнения промежуточной приемной гильзы и ее доработки при помощи композиций на основе кремний-органических соединений (силикона), позволяющей учесть все анатомические особенности порочной культи. Результаты. Разработанная технология обладает рядом преимуществ перед традиционной технологией изготовления приемных гильз: позволяет надежно фиксировать протезы с минимальными поршнеобразными движениями; улучшить косметические качества протезирования и внешний вид вследствие устранения дополнительных элементов крепления. Заключение. Разработанная технология не требует использования дополнительного оборудования и технологической оснастки, позволяет проводить сложное протезирование в условиях протезно-ортопедических предприятий, а также обладает рядом преимуществ перед традиционной технологией изготовления приемных гильз. Ключевые слова: протез предплечья, приемная гильза, протезирование, верхняя конечность, силиконовая композиция.

Restoration of structure, function, and sensation are critical after trauma or tumor resection of the hand. Thorough debridement, reconstruction of functional structures, and immediate soft tissue coverage are most effectively performed in a single stage within approximately 24 hours of the injury. Skin flaps provide robust, pliable, and cosmetically appropriate tissue that is not prone to contracture and that facilitates secondary reconstructive work. Muscle flaps retain indications for complex defects with substantial initial contamination or dead space, or for reanimation. In this article, the indications, options, and surgical techniques for free muscle flap reconstruction of upper limb defects are reviewed.

Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder characterized by upper limb defects and congenital heart defects (CHD), which are often simple septal and conduction defects, less frequently complex CHDs. We report on a 9 year-old boy with clinical and radiologic features of HOS consisting of bilateral asymmetric hypoplastic thumbs, generalized brachydactyly, limited supination due to radioulnar synostosis, and sloping shoulders, and intermediate atrioventricular canal defect (AVCD) with aortic coarctation. A de novo, previously described mutation, (Arg279ter) was identified in the TBX5 gene. Molecular characterization of this mutation was carried out due to the atypical CHD. In order to investigate whether the mutated transcript of TBX5 was able to escape the post-transcriptional surveillance mechanism and to produce a truncated TBX5 protein, we analyzed the TBX5 transcript, and protein pattern in HOS, and WT cardiac tissues. Our results demonstrate that the mutant TBX5 transcript is cleared by the cellular mechanism of surveillance. This data provides some support for the hypothesis that a dominant negative mutation, which strongly impairs the WT allele, might be too hazardous to be maintained. The literature suggests that HOS is relatively common among syndromes associated with AVCD.

Jacobsen syndrome (JS) is a disorder of developmental delay, growth retardation, thrombocytopenia, dysmorphic features, and cardiac abnormalities, among other congenital anomalies. JS is caused by contiguous gene deletion in distal chromosome 11q, generally varying in size from 7 to 20 Mb. Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder in which neurons are abnormally located in nodules along the edges of the lateral ventricles. PVNH can also be seen with other congenital anomalies, including a recurrent association with distal limb defects. Transverse limb defects have previously been reported in two patients with JS. We report on a patient with a 3.162 Mb interstitial deletion at chromosome region 11q24 overlapping the region commonly affected in JS. The patient had PVNH and a transverse limb reduction defect, with minimal typical findings of JS. This is the first report of PVNH associated with a microdeletion at chromosome 11q and may represent an expansion of the phenotypic spectrum associated with JS. This is the third report of transverse limb reduction defects in association with JS, supporting a widening of the skeletal phenotypic spectrum in JS to include more severe limb anomalies. ETS1 is proposed as a candidate gene for involvement in limb anomalies in JS. © 2013 Wiley Periodicals, Inc.

The pedicled paraumbilical flap is a reliable tissue transfer for hand and forearm reconstruction. However, its size, pedicle length and/or thickness limit its application in resurfacing of extensive defects of the upper limb. To conquer those limitations, this flap was pre-expanded for 10-24 weeks prior to transfer in 25 patients and used as a pedicle flap to cover upper extremity defects. Extensive defects of upper limb were reconstructed by the pre-expanded paraumbilical flaps. The flaps ranged in size from 10 cm × 8 cm to 30 cm × 14 cm. The donor sites were closed directly in all cases. All flaps survived, but two had partial flap necrosis due to venous congestion or infection. With pre-transfer expansion, a large, well-perfused abdominal pedicle flap can be raised and transferred based on the paraumbilical perforators. This pre-expanded flap might be useful in the patients who have the extensive upper limb defects and sufficient time to allow tissue expansion.

Sirenomelia, also known as the 'mermaid malformation/syndrome', is a rare, serious congenital anomaly characterized by variable degrees of fusion of the lower limbs and associated severe malformations of the lower vertebral and genitourinary systems. In this report, we describe a series of African patients with sirenomelia. We present the clinical and radiological features of four black South African patients and illustrate some of the rarer associated abnormalities, which include asymmetrical upper limb defects, not confined to the radial ray. The clinical phenotypic overlap between caudal dysgenesis, VACTERL association and sirenomelia in our patients is highlighted, lending support to the theory that these entities may be different manifestations of a single pathogenic process.

Injuries to upper limb has been on the increase and is invariably associated with significant soft tissue loss requiring a flap cover. Local tissue may not be available for cover in a majority of situations, necessitating import of tissue from a distant source. We have utilized the thoraco-umbilical flap taken from the trunk for this purpose. This flap is based on the perforators of the deep inferior epigastric artery that are maximally centred on the periumbilical region. This flap was used in 83 patients. The patients were observed for at least 3 weeks and any flap or donor site complications were recorded. The patients were again followed up at 3 months interval and the donor site scar was assessed. The flaps survived in 81 patients; there was marginal flap necrosis in five patients and partial flap necrosis in two patients. None of these patients required any additional procedure for coverage. The flap is technically easy to plan, almost effortless to drape around upper limb defects, with no significant donor site morbidity and also the post operative immobilization was fairly comfortable. The thoraco-umbilical flap thus is a very useful technique for coverage of the upper limb and is recommended as a first line flap for this purpose.

Acheiropodia is a very rare disease with autosomal recessive inheritance characterized by limb reduction defects. It has been described mainly in Brazil. The aim of this report is to describe the first reported cases in Argentina in two affected twins. Patients were reported to the National Registry of Congenital Anomalies of Argentina (RENAC). Both twins had limb reduction defect including hands, forearms, feet and fibulae. These patients are the first reported cases of acheiropodia syndrome in Argentina. Immigration from Brazil could explain this case in our population.

INTRODUCTION Thalidomide was available for use over-the-counter between 1958 and 1962, and more than 300 thalidomide-impaired people have been confirmed in Japan. Currently, thalidomide-impaired people are nearing the age of 50 years and sometimes require medical treatment or surgery. However, a sphygmomanometer cannot be used to measure the blood pressure in some thalidomide-impaired people because of upper-limb shortening or hypoplastic defects. We encountered a patient with thalidomide-related upper limb defects who required abdominal ovarian cystectomy. PRESENTATION OF CASE The patient was a 49-year-old woman (146.5 cm, 35.9 kg) with thalidomide-related upper-limb defects, but no dysplasia of the lower limbs, who underwent abdominal ovarian cystectomy. During the surgery, the patient's arterial blood pressure was monitored in her lower limbs by both non-invasive and invasive methods, and almost the same variations of the blood pressure between the invasive and non-invasive measurements were observed. DISCUSSION Usually, blood pressure measurements are performed in a non-invasive manner in the upper limbs, however, such measurement could not be performed in the present case. There are few reports of measurement of the blood pressure or surgery under anaesthesia in thalidomide-impaired patients, and we report here that it was useful to measure the blood pressure in the lower limbs in the current patient. Invasive arterial pressure measurements showed almost the same changes as the non-invasive pressure measurements, although the systolic blood pressure was 10–20 mmHg lower than the noninvasively measured systolic blood pressure. CONCLUSION Non-invasive blood pressure measurements in the lower limbs might be useful in thalidomide-impaired patients requiring blood pressure monitoring, but further studies are required to validate this method.

Resume Objectifs Le diagnostic antenatal d’une anomalie reductionnelle de membre pose des problemes medicaux et ethiques difficiles. Le diagnostic antenatal peut etre a l’origine de deux attitudes medicales opposees, soit une interruption medicale de grossesse, soit la mise en place d’un accueil specifique de l’enfant a la naissance. L’objectif est de realiser une enquete de pratiques et de rechercher s’il existe un seuil dans la gravite de la malformation a partir duquel l’interruption medicale de grossesse est acceptee. Materiel et methodes L’etude est realisee a partir d’un questionnaire adresse aux membres du Club Francophone de Medecine Fœtale. Resultats Elle permet l’analyse du devenir de 103 fœtus atteints d’une anomalie reductionnelle de membre. Elle decrit les modalites du diagnostic antenatal et la prise en charge des differentes malformations observees. Conclusion Les decisions concernant l’issue de la grossesse sont tres variables d’un couple a l’autre et d’une equipe medicale a l’autre. La demande des parents, apres information complete, doit etre accompagnee et soutenue sur le plan psychologique. La discussion collegiale d’une equipe pluridisciplinaire est necessaire. La responsabilite du medecin consiste a eviter aux parents, l’erreur d’un jugement domine par l’angoisse et la meconnaissance des consequences medicales. Qu’elle s’oriente vers la poursuite de la grossesse ou son interruption, la decision procede de la rencontre entre la confiance du couple et la conscience du medecin. La reflexion au cas par cas est necessaire car l’anomalie se situe parfois a la limite du tolerable pour les parents. Malgre la pratique systematique en France d’echographies a 12, 22, 32 semaines d’amenorrhee, cet examen n’est pas infaillible et toutes les anomalies reductionnelles des membres ne sont pas depistees en antenatal.

Background. The anterolateral thigh (ALT) flap has been widely described in reconstruction of the upper extremity. However, some details require refinement to improve both functional and aesthetic results. Methods. After reconstruction of upper extremity defects using thinned and innervated ALT flaps, functional and aesthetic outcomes were evaluated with the QuickDASH scale and a Likert scale for aesthetic assessment of free flaps, respectively. Results. Seven patients with a mean follow-up of 11.57 months and average flap thickness of 5 mm underwent innervation by an end-to-end neurorrhaphy. The average percentage of disability (QuickDASH) was 21.88% with tenderness, pain, temperature, and two-point discrimination present in 100% of cases, and the aesthetic result gave an overall result of 15.40 (good) with the best scores in color and texture. Conclusions. Simultaneous thinning and innervation of the ALT flap lead to a good cosmetic result and functional outcome with a low percentage of disability, which could result in minor surgical procedures and better recovery of motor and sensory function. Level of Evidence. IV.

On examination of the neonate, he had normal cry, reflex, colour and tone. Child had reduced left leg with absence of tibia and fibula, gross reduction of left femur, rotated left foot and syndactyly of left foot. (Figures1 and 2). On doing a digital x-ray of the neonate we found the radiological features matching the clinical picture (Figure 3). ___________________________________________ Junior Resident, Associate Professor, Department of Paediatrics, Junior Resident, Department of Obstetrics and Gynaecology, MKCG Medical College, India *Correspondence: dr.subham.scb@gmail.com (Received on 20 May 2015: Accepted after revision on 17 July 2015) The authors declare that there are no conflicts of interest Personal funding was used for this project.

We report a case of ectopic left upper limb located in the left side of the thorax in a 3-day neonate. The patient had dyspnea and deficiency of the left upper limb. Multidetector computed tomography (Fig 1A,B, arrow) revealed an “armlike” structure occupying most of the left side of the thoracic cavity; it included the humerus, ulna, radius, and palm. The bony structure was folded, with a mixed-intensity mass around it, consisting of muscle and fat (Fig 1C, arrow). It was firmly adherent to the left border of the mediastinum, leading to left pulmonary atelectasis and displacement of the heart. The lesion was removed by a radical surgical procedure. Congenital upper limb defects are extremely rare, with an incidence of 0.4%, and may be accompanied by other anomalies or syndromes [1] .A n absent limb located in the thorax has been especially rare; we have not been able to trace other similar records in the literature. In our case, the images offered detailed information to enable the patient to be scheduled for operation.

A 32-year-old primigravida, with low background risk at booking, referred to our fetal medicine department after a missing left lower limb in the fetus was diagnosed on scan at 26 weeks gestation. Hypoplastic left thigh and limb reduction defect were confirmed (figures 1 and 2) using 4D scan, and parents counselled. They remained committed to the pregnancy. …

It is well known that prenatal exposure of valproic acid (VPA) may be associated with the occurrence of neural tube defects (Robert and Gibaud, 1982). Additional adverse effects related to VPA exposure include craniofacial abnormalities, skeletal defects, brain defects, cardiovascular defects, and urogenital defects (DiLiberti et al., 1984; Winter et al., 1987; Huot et al., 1987; Jager-Roman et al., 1986; Martinez-Frias, 1990). Recently, radial ray reduction has been reported as a severe type of skeletal defect associated with VPA exposure (Jager-Roman et al., 1986; Huot et al., 1987; Verloes et al., 1990). We report two additional cases of this severe limb reduction defect as part of a broader pattern of altered morphogenesis in fetuses exposed to VPA and to confirm an association between such severe specific skeletal defects and VPA exposure. We briefly review teratologic studies in experimental animals which document the biologic plausibility of this association, and suggest that fetuses exposed to VPA undergo detailed prenatal ultrasonographic evaluation of the limbs.

We present a case-control study of limb reduction defects taken from autopsy material of the Pathology Department of the University of Athens from the year 1986 to 1990. During this period 1725 perinatal autopsies were performed, in which 34 neonates were found to have had a limb reduction defect (LRD) (1.97%). The cases were divided into five subgroups: transverse, intercalary longitudinal, split, and multiple types of LRD. Of all the cases, 44.17% involved the upper limb, 41.17% the lower limb, and 14. 70% both. Coexisting nonlimb malformations were found in 17 cases (50%), 5 with recognized syndromes and 12 with other associated defects. Risk factors correlated with LRD were found to be low birth weight (2500 g or less) and threatened abortion.

Limb deficiencies, the congenital absence or hypoplasia of a long bone and/or digits, vary greatly in their anatomy and etiology. Previous attempts to classify the range of possible phenotypes have not included all types of deficiencies. We present a new classification system, which includes all potential phenotypes. Infants with limb deficiencies were identified in the hospital-based Active Malformations Surveillance Program at Brigham and Women's Hospital in Boston, MA from the years 1972 to 1974 and 1979 to 2000. Affected infants were classified based on the anatomy and apparent cause of their deficiencies. The prevalence rate of all types of limb deficiency was 0.79/1,000. Upper limb deficiencies were significantly more common than lower limb deficiencies. There was no significant difference in frequencies between deficiencies on the left and right sides of the body. Longitudinal defects were more common than terminal transverse defects; intercalary defects were uncommon. Longitudinal defects were most likely to occur on the preaxial side of the limb. Almost half of affected infants had affected digits, with normal long bones. The most common apparent cause of limb deficiencies was vascular disruption defects (0.22/1,000), such as amniotic band-related limb deficiency. This new classification system includes deficiency of each long bone, as well as absence of any finger or toe. This system will make it possible to establish the prevalence of each specific phenotype. The large number of distinct apparent causes illustrates the marked etiologic heterogeneity of limb deficiencies.

Upper limb defects occur in approximately 3.4 per 10,000 live births. Major thumb defects represent 16% of these upper limb defects (Tay SC, Moran SL, Shin AY, et al. The hypoplastic thumb. J Am Acad Orthop Surg 2006;14:354-366). Embryologically, hand development begins by the fifth week. This occurs simultaneously with the growth and development of the cardiovascular, neurologic, and hematopoietic systems. Therefore, congenital anomalies seen in the hands of infants may indicate significant anomalies in these other systems, requiring a comprehensive physical evaluation. Although the cause of 40% to 50% of congenital hand anomalies is unknown (Gallant GG, Bora FW. Congenital deformities of the upper extremity. J Am Acad Orthop Surg 1996;4:163-171), several others have traced this to specific genetic mutations. Others are due to a variety of teratogenic effects (Sadler TW. Langman's Medical Embryology. 10th ed. Philadelphia: Lippincott Williams &Wilkins, Chapter 9, 2006:125-142). For the clinician, this paper has been organized to identify possible corresponding syndromes that may accompany specific thumb deformities.

The Ilizarov device and distraction osteogenesis method became very useful in correction and elongation of forearm defects. Two cases of forearm elongation with congenital transverse defect are described. The construction of the device is provided. During follow-up examination, 2 and 7 years after the treatment, good clinical results were achieved in both patients with the use of upper limb prosthesis employing the patient's own elbow joint. Presented application of the Ilizarov method can significantly improve possibilities for the use of prosthesis in patients with congenital upper limb defects and result in better cosmetic and functional outcome.

Background Raising perforator flaps is said to be a tedious procedure. The benefits, however, are great. In adults, perforator flaps have proved their usefulness and reliability in various clinical situations. In children, donor sites for free flaps are particularly scarce because of the need for a long and reliable vascular pedicle of sufficient size. There is also the need to minimize donor-site morbidity from aesthetic, functional, and psychological perspectives. Methods The authors present a series of 23 consecutive free perforator flaps performed by the first author in 20 children; ages at the time of operation ranged from premature (born at 28 weeks) to 16 years (mean age, 7 years 5 months). Three children presented with upper limb defects; the remaining 17 children sustained major soft-tissue defects of the lower limb. All the lesions necessitated extensive coverage with a free flap. Flaps used in this series included nine deep inferior epigastric artery perforator flaps, seven thoracodorsal artery perforator flaps, and seven compound ("chimera") thoracodorsal artery perforator flaps. Results All flaps but one were successful. With a follow-up of up to 7 years, the results in this series compare favorably with those of perforator flaps in adults or pediatric free flaps in the literature. Conclusions In children, as in adults, perforator flaps are a valuable alternative to the traditional muscle or myocutaneous free flap. Because of the added advantage of reducing donor-site morbidity, perforator flaps have become the authors' preferred option in reconstructive cases in children.

Mutations in the T-box transcription factor TBX5 cause Holt-Oram syndrome (HOS), an autosomal-dominant condition characterized by a familial history of congenital heart defects and preaxial radial ray upper limb defects. This review summarizes recent developments in the study of TBX5 as it relates to congenital heart disease and the pathology of HOS.Currently, 37 mutations in TBX5 have been found in patients with HOS. Most of these mutations cause premature truncation of the primary TBX5 transcript, thereby presumably causing haploinsufficiency. Conversely, missense mutations diminish the interaction of TBX5 with other transcription factors and reduce nuclear localization of mutant protein. Although mutations are found throughout the TBX5 gene, no evidence exists to suggest that genotype affects the location of heart and limb defects or the severity of HOS manifestation. However, genetic background, and to a lesser extent, environmental and stochastic modifiers are believed to influence greatly the severity of HOS manifestation and may account for the large variation seen in the severity of defects, even among members of the same kindred. Careful clinical examination of patients who seek treatment with heart and limb malformations is necessary to avoid misdiagnosis of similar congenital conditions. With the proper examination, TBX5 mutations can be identified in more than 70% of patients with a clinical diagnosis of HOS.Genetic analysis of patient populations and the biochemical characterization of the mutated proteins have provided considerable insight into the function of TBX5 in cardiac development and disease pathology. Novel discoveries await as these two paradigms merge.

There have been a small number of documented cases of isolated congenital diaphragmatic hernia and ipsilateral limb defects. Early cervical neural crest injury has been postulated as the mechanism behind the coexistence of these two defects. We present a case of left-sided congenital diaphragmatic hernia and ipsilateral radial ray defect consisting of thumb hypoplasia and absent radius. Our patient is an adult who presented for reproductive counselling providing an opportunity for long-term follow-up.

The results of the clinical and radiographic study of 7 patients support the view of a unimodal and rather narrow phenotypic spectrum in the Brachmann-de Lange syndrome (BDLS) and reject the existence of a “classic” type of patient and a “mild phenotype” without upper limb defects who survive with moderate to severe mental retardation. Similarity among all patients is greater than their phenotypic differences. Strict clinical definition of the syndrome warrants easier access to the still unknown cause, most probably a single gene mutation with autosomal dominant inheritance. © 1993 Wiley-Liss, Inc.

This report concerns two sibs from a consanguineous Sudanese family with microgastria-limb reduction defect associated with hydrocephalus and agenesis of corpus callosum. We suggest that these cases together with other previously reported cases of central nervous system (CNS) anomalies associated with microgastria-limb reduction defect could represent an autosomal recessive syndrome differing from the classical microgastria-limb reduction defect by its severity, presence of CNS anomalies and its pattern of inheritance.

We described a male infant with a spectrum of anomalies compatible with the diagnosis of 'disorganization-like syndrome'. The infant had a partial foot arising from the right buttock, an absent right kidney, and a shortened right leg with severe non-positional talipes equinovarus. The infant's karyotype was 47,XXY. The right common iliac artery was one half of the expected diameter. The limb reduction defect seen in this case of disorganization (Ds) may have had a vascular aetiology.

Upper limb involvement in the Klein--Waardenburg (K--W) syndrome is documented in two affected sibs and in four other previously reported patients. In addition to the key facial and auditory findings observed in the Waardenburg syndrome type I, these patients have such bilateral upper limb defects as hypoplasia of the musculoskeletal system, flexion contractures, fusion of the carpal bones, and syndactyly. The cause of the K--W syndrome is not known although there is some evidence for autosomal dominant inheritance, but further documentation is needed before this can be considered conclusive.

The forearm is a convenient donor site for local flap cover in upper limb defects. Island flaps based on either of the major forearm arteries share properties suiting them for reconstruction from elbow to fingertips. The ulnar artery flap has some advantages over the radial flap, especially the easy management, low morbidity and better aesthetics of the donor site. Illustrative cases of proximally and distally based island ulnar flaps are presented.

Nager's syndrome, which has the facial features of Treacher Collins syndrome, preaxial upper limb defects, short stature, and frequently subnormal intelligence, is very rare. Five new cases have been collected. In four, there was virtually total absence of the soft palate. This has been described in two patients in the past. Differing methods of correcting this are presented.

A woman who had previously given birth to a child with tetra-amelia was sonographically diagnosed to have again conceived a fetus with the same anomaly. Although recurrent tetra-amelia is extremely rare, ultrasonographic imaging proved to be very useful in detecting this limb reduction defect in early pregnancy.