Defects In Upper Limb Research Articles

New thoracodorsal artery perforator (TAPcp) flap with capillary perforators for reconstruction of upper limb

Thoracodorsal artery perforator (TAP) flap is not yet popularised because the dominant large muscle perforators are often absent. Even in those cases, small capillary perforators exist around the proximal portion of the lateral border of the latissimus dorsi muscle, and they have a potential of a large skin territory. To overcome the weakness of thoracodorsal artery muscle perforator (TAP-MCp) and septocutaneous perforator (TAP-SCp) flaps, we present a new TAP flap with capillary perforators (TAPcp) flap. A total of 14 patients with upper-limb defects were repaired with free TAPcp flap. Among them were three combined TAP flaps with vascularised scapula bone flap and eight flow-through flaps. Recipient sites were one axilla, three upper arms, one elbow, two forearms and seven hands. The only postoperative complication was a partial necrosis of the flaps. A new TAP flap with capillary perforators is very useful for the reconstruction of upper limb. The advantage is easier elevation within short time (does not require intramuscular dissection) with long or short vascular pedicle. The flap can be elevated in a supine position, and even lateral descending branch can be a pedicle vessel. The flap can be a flow-through flap and is less invasive, because the remaining muscle can be preserved along with the motor nerve.

A novel malformation complex of bilateral and symmetric preaxial radial ray-thumb aplasia and lower limb defects with minimal facial dysmorphic features: a case report and literature review

IntroductionRadial hemimelia is a congenital abnormality characterised by the partial or complete absence of the radius. The longitudinal hemimelia indicates the absence of one or more bones along the preaxial (medial) or postaxial (lateral) side of the limb. Preaxial limb defects occurred more frequently with a combination of microtia, esophageal atresia, anorectal atresia, heart defects, unilateral kidney dysgenesis, and some axial skeletal defects. Postaxial acrofacial dysostoses are characterised by distinctive facies and postaxial limb deficiencies, involving the 5th finger, metacarpal/ulnar/fibular/and metatarsal.Case presentationThe patient, an 8-year-old-boy with minimal craniofacial dysmorphic features but with profound upper limb defects of bilateral and symmetrical absence of the radius and the thumbs respectively. In addition, there was a unilateral tibio-fibular hypoplasia (hemimelia) associated with hypoplasia of the terminal phalanges and malsegmentation of the upper thoracic vertebrae, causing effectively the development of thoracic kyphosis.ConclusionIn the typical form of the preaxial acrofacial dysostosis, there are aberrations in the development of the first and second branchial arches and limb buds. The craniofacial dysmorphic features are characteristic such as micrognathia, zygomatic hypoplasia, cleft palate, and preaxial limb defects. Nager and de Reynier in 1948, who used the term acrofacial dysostosis (AFD) to distinguish the condition from mandibulofacial dysostosis. Neither the facial features nor the limb defects in our present patient appear to be absolutely typical with the previously reported cases of AFD. Our patient expands the phenotype of syndromic preaxial limb malformation complex. He might represent a new syndromic entity of mild naso-maxillary malformation in connection with axial and extra-axial malformation complex.

Functional analysis of the novel TBX5c.1333delC mutation resulting in an extended TBX5 protein

BackgroundAutosomal dominant Holt-Oram syndrome (HOS) is caused by mutations in the TBX5 gene and is characterized by congenital heart and preaxial radial ray upper limb defects. Most of the TBX5 mutations found in patients with HOS cause premature truncation of the primary TBX5 transcript. TBX5 missense mutations alter the three-dimensional structure of the protein and result in failed nuclear localization or reduced binding to target DNA. In this study we present our functional analyses of the novel and unusual c.1333delC mutation found in a patient with classical HOS.MethodsThe functional impact of this novel mutation was assessed by investigating the intracellular localization of the resulting TBX5 protein and its ability to activate the expression of its downstream target ANF.ResultsThe deletion of the cytosine is the first TBX5 frameshift mutation predicted to result in an elongated TBX5 protein with 74 miscoding amino acids and 62 supernumerary C-terminal amino acids. The c.1333delC mutation affects neither the nuclear localization, nor its colocalization with SALL4, but severely affects the activation of the ANF promoter.ConclusionThe mutation c.1333delC does not locate within functional domains, but impairs the activation of the downstream target. This suggests that misfolding of the protein prevents its biological function.

Distinct Expression and Function of Alternatively Spliced Tbx5 Isoforms in Cell Growth and Differentiation

Mutations in the T-box transcription factor Tbx5 cause Holt-Oram syndrome, an autosomal dominant disease characterized by a wide spectrum of cardiac and upper limb defects with variable expressivity. Tbx5 haploinsufficiency has been suggested to be the underlying mechanism, and experimental models are consistent with a dosage-sensitive requirement for Tbx5 in heart development. Here, we report that Tbx5 levels are regulated through alternative splicing that generates, in addition to the known 518-amino-acid protein, a C-terminal truncated isoform. This shorter isoform retains the capacity to bind DNA, but its interaction with Tbx5 collaborators such as GATA-4 is altered. In vivo, the two spliced isoforms are oppositely regulated in a temporal and growth factor-dependent manner and are present in distinct DNA-binding complexes. The expression of the long isoform correlates with growth stimulation, and its reexpression in postnatal transgenic mouse hearts promotes hypertrophy. Conversely, the upregulation of the short but not the long isoform in C2C12 myoblasts leads to growth arrest and cell death. The results provide novel insight into posttranscriptional Tbx5 regulation and point to an important role not only in cell differentiation but also in cell proliferation and organ growth. The data may help analyze genotype-phenotype relations in patients with Holt-Oram syndrome.

Descriptive epidemiology of Cornelia de Lange syndrome in Europe

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome consisting of characteristic dysmorphic features, microcephaly, hypertrichosis, upper limb defects, growth retardation, developmental delay, and a variety of associated malformations. We present a population-based epidemiological study of the classical form of CdLS. The data were extracted from the database of European Surveillance of Congenital Anomalies (EUROCAT) database, a European network of birth defect registries which follow a standard methodology. Based on 23 years of epidemiologic monitoring (8,558,346 births in the 1980-2002 period), we found the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of cases, fetal deaths 2.8% (3/106), and terminations of pregnancy following prenatal diagnosis 5.7% (6/106). The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%). In the last 11 years, as much as 68% of cases with major malformations were not detected by routine prenatal US. Live born infants with CdLS have a high first week survival (91.4%). All patients were sporadic. Maternal and paternal age did not seem to be risk factors for CdLS. Almost 70% of patients, born after the 37th week of gestation, weighed <or=2,500 g. Low birth weight correlated with a more severe phenotype. Severe limb anomalies were significantly more often present in males.

Acrofacial dysostosis syndrome type Rodriguez: Prenatal diagnosis and autopsy findings

A new lethal form of acrofacial dysostosis (AFD) syndrome was delineated by Rodriguez et al. [Rodriguez et al. (1990); Am J Med Genet 35:484-489]. We report on a male fetus with mandibulofacial dysostosis, including phocomelia-like upper limb deficiencies and lower limb anomalies which are characteristic of AFD Rodriguez type. The diagnosis was made on prenatal sonogram at 20 and at 24.1 weeks gestation. The severity of the upper limb defects, the involvement of lower limbs, and the absence of eyelid coloboma and polythelia excluded the possibility of other conditions associated with acrofacial dysostosis (AFD) including Nager acrofacial dysostosis syndrome (NADS) and postaxial acrofacial dysostosis syndrome (POADS). This case further delineates the AFD syndrome type Rodriguez.

Lengthening of congenital forearm stumps

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.

Free Perforator Flaps in Children

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. 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. 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. 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.

Corneal Endothelial Abnormalities Associated With Thalidomide Toxicity

To describe bilateral corneal endothelial abnormalities associated with thalidomide toxicity. Observational case report. A 30-year-old man, born with bilateral hypoplastic upper limb defects (phocomelia) caused by thalidomide toxicity, presented with bilateral symmetrical corneal endothelial changes resembling guttata without corneal edema. Pachymetry, specular microscopy, and confocal microscopy were performed. Biomicroscopy findings over a 10-year follow-up showed no changes. Nonprogressive bilateral corneal endothelial changes resembling cornea guttata should possibly be included in the ocular manifestations of thalidomide toxicity. We postulate that thalidomide may have affected the migration and development of the mesenchymal neural crest cells, which are the developmental precursors of the corneal endothelium and stroma.

TBX5 mutations and congenital heart disease: Holt-Oram syndrome revealed.

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.

The free lateral arm flap in reconstructive hand surgery

Microsurgical tissue transplantation has provided a great advance in reconstructive surgery, especially regarding upper limb defects. Compared to conventional pedicled flaps, mobilisation can occur earlier, hospital stay is shorter and no additional interventions for pedicle detachment and flap inset are needed. The lateral arm flap is an exceptionally versatile free flap with straightforward dissection and low donor site morbidity. End-to-side anastomosis preserves blood flow through the main arteries to the hand and reduces the risk of vascular compromise of the hand, which is especially important in case of severe hand injuries. Sixteen patients who underwent hand reconstruction using the lateral arm free flap are reviewed. All arterial anastomoses were conducted in end-to-side-technique either to the radial or the ulnar artery. There was no total- or partial-flap failure and only one revisional procedure due to a haematoma under the anastomosis. Eight flaps required secondary defatting, combined with removal of osteosynthesis material or tenolysis. From our point of view the free lateral arm flap is a very reliable and versatile method to resurface small and medium sized hand defects.

Homozygous and heterozygous inheritance of PAX3 mutations causes different types of Waardenburg syndrome

Type I Waardenburg syndrome (WS-I) is an auditory-pigmentary syndrome caused by heterozygous loss of function mutations in the PAX3 gene. Klein-Waardenburg syndrome (WS-III) is a very rare condition and represents an extreme presentation of WS-I, additionally associated with musculoskeletal abnormalities. We present an 18-months old Turkish child with typical Klein-Waardenburg syndrome (WS) including dystopia canthorum, partial albinism, and upper-limb defects. The child was born to a consanguineous couple and both parents had WS-I. We screened the entire coding region of the PAX3 gene for mutations and identified a novel missense mutation, Y90H, within the paired box domain of PAX3. Both parents were heterozygous for the mutation and the proposita was homozygous. This is the third report of a homozygous PAX3 mutation causing the WS-III phenotype. Molecular analysis of four additional Turkish families with variable clinical expression of WS-I identified two missense mutations, one splice-site mutation, and one small insertion in the PAX3 gene.

Tbx3 impinges on the p53 pathway to suppress apoptosis, facilitate cell transformation and block myogenic differentiation.

Tbx3 is a member of the T-box family of transcription factors. Mutations in Tbx3 cause ulnar-mammary syndrome, an autosomal dominant disorder characterized by upper limb defects, apocrine-gland defects including mammary hypoplasia, and tooth, hair and genital defects. In cell culture, Tbx3 and its close relative Tbx2 are capable of immortalizing mouse embryo fibroblasts. We show that expression of Tbx3 together with Myc or oncogenic Ras (H-Ras(Val17)) leads to efficient transformation of mouse embryo fibroblasts. Oncogene cooperation by Tbx3 correlates with an ability of Tbx3 to suppress the induction of p19ARF and p53 that is typically caused by overexpression Myc and Ras, and to protect against Myc-induced apoptosis. Whereas Tbx3 is capable of interfering with apoptosis caused by excessive Myc levels, a Tbx3 mutant lacking its C-terminal repression domain shows no anti-apoptotic activity and fails to repress levels of p19ARF or p53. Consistent with an ability to suppress p53 pathway function, we find that Tbx3, but not a Tbx3 C-terminal mutant, efficiently blocks myogenic differentiation of C2C12 myoblasts. Our results support the idea that deregulation and/or excessive levels of Tbx3 may have oncogenic potential in vivo.

Rotation Fasciocutaneous Flap Repair of Upper Limb Defects

Rotation Fasciocutaneous Flap Repair of Upper Limb Defects

Pedicle Flaps of the Upper Limb: Vascular Anatomy, Surgical Technique and Current Indications

This is English-language edition of Les Lambeaux Arteriels Pedicules du Membre Superieur , published in 1990. The list of 40 contributors from around world attests to international collaboration achieved by editors. As Hentz states in foreword, motivation for this English edition lies in unsubstantiated impression that surgeons in the United States are less experienced than their international colleagues in use of contemporary arterialized pedicle for reconstruction of cutaneous defects in upper limb. The book includes 24 chapters with individual references and a comprehensive index. The first three chapters describe historic evolution of study of cutaneous vascularity of upper limb with references to Esser, Littler, and others. Basic definitions of arterial island and peninsular flaps are provided along with standard classification of skin and fasciocutaneous and musculotaneous flaps based on pertinent vascular anatomy nourishing each flap.

A Significant Feature of Nagerʼs Syndrome

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.

The ulnar island flap in hand and forearm reconstruction

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.