Hand Anomalies Research Articles

KBG syndrome involving a single-nucleotide duplication in ANKRD11.

KBG syndrome is a rare autosomal dominant genetic condition characterized by neurological involvement and distinct facial, hand, and skeletal features. More than 70 cases have been reported; however, it is likely that KBG syndrome is underdiagnosed because of lack of comprehensive characterization of the heterogeneous phenotypic features. We describe the clinical manifestations in a male currently 13 years of age, who exhibited symptoms including epilepsy, severe developmental delay, distinct facial features, and hand anomalies, without a positive genetic diagnosis. Subsequent exome sequencing identified a novel de novo heterozygous single base pair duplication (c.6015dupA) in ANKRD11, which was validated by Sanger sequencing. This single-nucleotide duplication is predicted to lead to a premature stop codon and loss of function in ANKRD11, thereby implicating it as contributing to the proband's symptoms and yielding a molecular diagnosis of KBG syndrome. Before molecular diagnosis, this syndrome was not recognized in the proband, as several key features of the disorder were mild and were not recognized by clinicians, further supporting the concept of variable expressivity in many disorders. Although a diagnosis of cerebral folate deficiency has also been given, its significance for the proband's condition remains uncertain.

Identification of Associated Genes and Diseases in Patients With Congenital Upper Limb Anomalies

Purpose: Congenital upper limb anomalies (CULA) can present isolated or as a part of a syndrome or association. Therefore, surgeons dealing with CULA should be aware of associated diseases and anomalies. The newly accepted Oberg, Manske, and Tonkin (OMT) classification allows for registration of a wide spectrum of CULA. Therefore, providing associated diseases for each hand anomaly in the classification would aid differential diagnosis formulation in clinic and investigation of causal genes in research. The first aim of this study was to review the Human Phenotype Ontology (HPO) database for diseases and causative genes that can be related to hand anomalies present in the OMT classification. The second aim was to relate associated anomalies and inheritance patterns to improve differentiation between the diseases. Methods: The HPO database was reviewed for all diseases with a known causative gene related to hand anomalies. All hand phenotypes were classified according to the OMT classification; nonhand phenotypes were classified into anatomical groups. TIBCO Spotfire Software was used to visualize the contribution of each anatomical group to a given disease and to prioritize diseases based on this contribution. Results were compared with literature cases and to a current HPO tool, Phenomizer. Results: In total, 514 hand phenotypes were obtained, 384 could be classified in the OMT classification, and 1403 diseases could be related to the OMT classification. Differentiation between diseases is illustrated by examples. Comparison to recently published hand phenotypes reveals that all were present in our data set. Gene prioritization using our methodology was better than Phenomizer in 4/5 examples. Conclusions: We present an OMT-classification-based methodology to aid clinicians in differential diagnosis formulation in patients with CULA. Furthermore, we enable discrimination between the diseases by providing insight in the differences in disease presentation. Gene prioritization and visualization in the proposed system outperforms systems in current use.

The Application of the Oberg, Manske, and Tonkin Classification in Clinic

Introduction: Congenital upper limb anomalies (CULA) exhibit a wide spectrum of phenotypic manifestations. To describe the full nature of all anomalies, the Oberg, Manske, and Tonkin (OMT) classification was developed. The OMT classification aims to provide a classification which better fits the current concepts of the etiology and allow combined documentation of all anomalies present in a single limb. The introduction of the OMT classification was succeeded by multiple validation studies regarding its clinical application. However, all studies were mainly aimed to test usability of the classification and were not consistent in the classification strategy: In some studies, all anomalies were classified as suggested by the initiators, whereas others only used one diagnoses per limb. Therefore, the aim of this study was to evaluate the various classification strategies used with the OMT classification. Methods: We retrospectively reviewed all patients visiting the Erasmus MC Team for Congenital Hand and Upper Limb Malformations in the Sophia Children’s Hospital between December 2014 and February 2012. All congenital anomalies of both limbs individually were classified according to the OMT scheme as proposed by Tonkin et al; furthermore, all associated anomalies were recorded. In compound hand phenotypes, every hand anomaly present was classified to best describe the clinical features of every patient. To evaluate which hand anomalies commonly required multiple diagnoses used within one patient, the mean number of diagnosis and 95% confidence interval (CI) were calculated and plotted for each OMT class and diagnose specifically. To evaluate whether multiple OMT-term use was effective to discriminate different cohorts of patients, the group characteristics of patients requiring one OMT diagnosis versus patients requiring multiple OMT diagnoses were studied. Results: In total, 736 patients were eligible for inclusion and 953 OMT diagnoses were registered; 449 were unilateral (219 left-handed, 230 right-handed) and 504 were bilateral. The average number of diagnosis for each patient was 1.29 (95% CI, 1.25-1.34). In 20.5% of the patients ( n = 155), a combination of OMT diagnoses was used to describe the observed anomalies. The total number of unique combinations of OMT diagnosis was 101, of which 77 combinations were only used once and 24 were used repeatedly. We illustrate that in radial polydactyly, additional OMT diagnosis was often used to convey differentiating characteristics, such as additional ulnar polydactyly, the combination of which was more often observed in patients with a syndromal cause of the anomaly. Conclusion: We conclude that the strategy used in applying the OMT classification is of eminent importance for optimizing the discriminating features of the OMT classification. As suggested by the initiators, all terms necessary to convey the full nature of the anomaly should be used. We illustrate our point using case examples for radial polydactyly.

Correction of Brachymetatarsia and Medial Angulation of the Great Toe of Apert Foot By Distraction Osteogenesis: A Review of 7 Years of Experience.

Apert foot anomalies may cause severe problems such as pain and development of callus formation related to weight redistribution, problems with footwear, and gait disturbances that may limit their daily activities. The main purpose of this study was to review our experience with distraction osteogenesis for the correction of brachymetatarsia and the great toe angulation of the patients with Apert syndrome. This study retrospectively reviewed 7 patients (14 extremities) followed up for Apert syndrome who underwent distraction for the correction of bilateral congenital brachymetatarsia and angulation of the great toe between 2004 and 2008. Correction of the metatarsal inclination angle, the medial angulation of the great toe, the percentage of lengthening, and lengthening rates of distracted bones were evaluated. Patients ranged in age from 4 to 8 years at the distraction operation, with a mean age of 5.4±1.3 years, and the average length of follow-up was 86.6±21.0 months. The length of the first metatarsal bone increased significantly from the average length of 32.6±5.7 mm to an average of 46.7±6.5 mm (P<0.001). The mean lengthening rate and lengthening percentages of distracted bones were 0.4%±0.1%/month and 30.2%±6.4%/month, respectively. Preoperative and postoperative metatarsal inclination angles were at a mean of 43.8±5.12 and 32.6±3.8, respectively, and the correction of metatarsal inclination was considered as statistically significant (P<0.001). The mean angulation of the great toe reduced significantly from 49.8±11.76 to 13.2±8.5 degrees after distraction (P<0.001). Minor complications such as pin loosening, pin-tract infection, and early union that required reoperation were observed in 5 extremities (35.7%). Anatomic features of Apert foot may lead to complaints that may limit patients' daily activities and require as much attention as associated hand and craniofacial anomalies. Distraction appears to be an effective and safe approach for the simultaneous correction of the shortness of the first ray and medial angulation of the great toe. Level IV.

Larsen syndrome

Larsen syndrome is a rare inherited disorder characterized by congenital dislocation of multiple joints along with other anomalies of heart, face, hands and bones. Larsen syndrome was first described in 1950 by Larsen, Schottstaedt and Bost. In the present report, we describe a 10 year old girl who presented with mid facial hypoplasia with depressed nasal bridge, high arched palate, bilateral talipes equinovarus and high arched feet. On examination, she had short stature (HAZ -3.5 SD) with hyperextension of knee joint, fixed flexion of elbow joint. Awareness of this condition and associated complications may help in management and follow up of these patients.

Congenital hand anomalies in Upper Egypt.

Background:Congenital hand anomalies are numerous and markedly variant. Their significance is attributed to the frequent occurrence and their serious social, psychological and functional impacts on patient's life.Patients and Methods:This is a follow-up study of 64 patients with hand anomalies of variable severity. All patients were presented to Plastic Surgery Department of Sohag University Hospital in a period of 24 months.Results:This study revealed that failure of differentiation and duplication deformities were the most frequent, with polydactyly was the most common anomaly encountered. The mean age of presentation was 6 years and female to male ratio was 1.46:1. Hand anomalies were either isolated, associated with other anomalies or part of a syndrome.Conclusion:Incidence of congenital hand anomalies in Upper Egypt is difficult to be estimated due to social and cultural concepts, lack of education, poor registration and deficient medical survey. Management of hand anomalies should be individualised, carefully planned and started as early as possible to achieve the best outcome.

Congenital Hand Differences.

Congenital hand differences are frequently encountered by pediatric plastic surgeons. These anomalies may cause significant emotional and functional challenges for children. Pediatric plastic surgery nurses should have a basic understanding of common congenital hand differences and related treatment options to facilitate patient education and postoperative care. This article discusses clinical findings and management of 4 of the most common hand anomalies: syndactyly, polydactyly, thumb hypoplasia, and cleft hand. The goals of surgical treatment are to maximize hand function and aesthetics with minimal adverse outcomes.

Strategies in Treatment of Congenital Hand Malformation

The aim of the treatment of congenital hand anomalies is to achieve a functional improvement in order to enable patients to lead an independent life. As parents have to decide for their children early in life, they have to be convinced of the treatment proposal. One and the same disease may present with various individual pathologies, which may require intraoperative changes of the previously planned procedure. Because of possible changes during growth, doctors have to keep in touch with the patients up to the end of adolescence. This article presents our algorithm and surgical techniques for dealing with children with hand malformations.

Intranatal Torsion of Polydactyly: A Rare Event

ABSTRACTPolydactyly is one of the most common anomalies of hand and/or foot. Postnatal torsion of pedunculated polydactyly is a well known complication but intranatal torsion has been infrequently described in published literature. Here, we describe a case of pedunculated ulnar polydactyly which was gangrenous at birth due to intranatal torsion. Controversies surrounding the management of narrow pedicled pedunculated polydactyly by traditional method of suture ligation at base are also discussed.

The Craniofacial and Upper Limb Management of Nager Syndrome.

Nager syndrome is a rare condition characterized by craniofacial and upper limb abnormalities. It is commonly mistaken for Treacher Collins syndrome, with which it shares the same craniofacial phenotype. However, patients with Treacher Collins do not exhibit hand anomalies, which are seen in patients with Nager syndrome. This paper reviews the multidisciplinary management of patients with Nager syndrome who were treated at the Australian Craniofacial Unit, Adelaide and the Erasmus Medical Centre, Rotterdam. The database of both units was scrutinized and the case-notes of the patients with Nager syndrome were reviewed. Data was collected on patient demographics, surgical management, complications, and outcome. Nine patients (6 M:3 F) were identified with Nager syndrome, with a mean age at presentation of 3.7 years (range 8 days to 11.8 years). The mean follow-up time was 2.2 years (2 months to 19 years). SF3B4 mutation was noted in 2 patients and 1 patient had an X:9 translocation. Seven (77.8%) had obstructive sleep apnoea, with 5 patients diagnosed as severe obstructive sleep apnoea. Four patients had pollicization of their index, 2 patients had excision of extra radial digits and 1 patient underwent thumb duplication correction. Craniofacial surgery included mandibular advancement in 5 patients, temporo-mandibular joint reconstruction in 2 patients, and a genioplasty in 1 patient. Nager syndrome is a rare acrofacial dysostosis syndrome that is best managed within the realms of a multidisciplinary team. The authors would advocate early pollicization in patients with thumb anomalies to prevent any impairment in manual dexterity.

Interstitial 9p24.3 deletion involving only DOCK8 and KANK1 genes in two patients with non-overlapping phenotypic traits

Chromosome 9p deletion represents a clinically and genetically heterogeneous condition characterized by a wide spectrum of phenotypic manifestations and a variable size of the deleted region. The deletion breakpoint occurs from 9p22 to 9p24 bands, and the large majority of cases have either terminal deletions or translocations involving another chromosome. Here we report on two patients with similar inherited interstitial 9p24.3 deletion involving only DOCK8 and KANK1 genes. Interestingly, the two patients showed non-overlapping phenotypic traits ranging from a complex phenotype in one to only trigonocephaly with minor dysmorphic features and hand anomalies in the other one. The factors underlying the phenotypic variation associated with seemingly identical genomic alterations are not entirely clear, even if smaller variants, single-nucleotide changes, and epigenetic or stochastic factors altering the expression of genes within functionally relevant pathways have been recently shown to contribute to phenotypic variation. We discuss the role of the two genes and propose possible explanations for the clinical heterogeneity of the phenotype of the two patients.

Supernumerary Carpal Bones in Larsen Syndrome: A Review of the Literature and Case Study

Larsen syndrome is a rare congenital disorder commonly associated with dysmorphic facies, large joint dislocations, equinovarus or equinovalgus foot deformities, and various hand anomalies, including supernumerary carpal bones. The authors present a case of Larsen syndrome with bilateral supernumerary carpal bones as the sole clinical manifestation. A literature review investigating skeletal anomalies in patients with Larsen syndrome was performed and revealed that the present case represents a unique presentation of this disorder, lacking all of the major clinical features previously described in the literature. An approach to patients with supernumerary carpal bones is discussed.

Ghazi M Rayan and Joseph Upton III: Congenital Hand Anomalies and Associated Syndromes

The book starts with a reminder from the 1982 Lamb study, of a birth incidence for upper limb malformations of 11 per 10,000 live births, 51 % being bilateral and 17 % associated with multiple malformations. Limb defects are more prevalent in boys, with pre-term, post-term and multiple births, and in the offspring of older mothers. Classifications are based on those of the American Society for Surgery of the Hand and the International Federation of Societies for Surgery of the Hand. The classification encompasses several categories, including failure of formation, defective differentiation, duplication, undergrowth and overgrowth, constriction bands and general skeletal anomalies. This classification blends well with our current understanding of the aetiology of limb defects. The book covers aetiology only minimally but briefly alludes to the key molecular mechanisms. Given the rapid pace of progress in understanding the molecular genetics of limb development, it would be difficult for a text book to remain in date and therefore appropriate for the reader to look elsewhere. I would strongly recommend this as an educational resource to understand the use of specific terms describing hand malformations and as a practical tool to aid with diagnosis of hand anomalies. The resource of photographs is unique. This is a long-awaited comprehensive review of congenital hand anomalies and associated syndromes that will appeal to clinical geneticists and hand surgeons alike. The illustrations are outstanding, with a combination of photographs, X-rays, illustrative diagrams, plaster moulds and CT scans. As this was written by two hand surgeons, the clinical genetics reader may find some of the surgical photographs unsettling, but they are helpfully linked to pre-operative photographs and serve a purpose reminding us of the internal anatomy of the limb and how this, too, may be abnormal. There are descriptions of 127 associated syndromes and 37 congenital differences. Although this is a highly specialised field, the breadth of conditions covered alludes to the high frequency of limb anomalies in genetic syndromes. Syndromic descriptions include photographs of the syndromologist, hallmarks, background, aetiology and presentation, and a list of associated anomalies. A clear systematic approach is used with Chapters 1 subdivided into tumours, enchondromas, osteochondromas, neurofibromas, vascular malformations, congenital contractures, and congenital joint laxity/instability. Chapters 2 and onwards are classified by the anatomical location (elbow, forearm, hand, thumb, digits, and skin).

EP09.10: Can you give me a hand? Diagnosing and understanding the clinical significance of fetal hand anomalies in obstetric ultrasound

EP09.10: Can you give me a hand? Diagnosing and understanding the clinical significance of fetal hand anomalies in obstetric ultrasound

FGFR2 mutation in a patient without typical features of Pfeiffer syndrome – The emerging role of combined NGS and phenotype based strategies

Pfeiffer syndrome (MIM: #101600) is a rare autosomal dominant disorder classically characterized by limb and craniofacial anomalies. It is caused by heterozygous mutations in the fibroblast growth factor receptors types 1 and 2 (FGFR1 and FGFR2).We applied a next generation sequencing (NGS) panel approach comprising all 2877 genes currently known to be causative for one or more Mendelian diseases combined with the phenotype based computational tool PhenIX (Phenotypic Interpretation of eXomes).We report on a patient presenting with multiple anomalies of hands and feet including brachydactyly and symphalangism. No clinical diagnosis could be established based on the clinical findings and testing of several genes associated with brachydactyly and symphalangism failed to identify mutations. Via next generation sequencing (NGS) panel approach we then identified a novel de novo missense FGFR2 mutation affecting an amino acid reported to be mutated in Pfeiffer syndrome. Since our patient shows typical radiological findings of Pfeiffer syndrome in hands and feet but at the same time lacks several characteristic features such as clinical signs of craniosynostosis and prominent eyes we suggest introducing the term “FGFR2 associated phenotypes” for similar cases.Our results highlight the emerging role of combined NGS and phenotype based bioinformatics strategies to establish clinical diagnoses.

Radiological Features in Patients with Short Stature Homeobox-Containing (SHOX) Gene Deficiency and Turner Syndrome before and after 2 Years of GH Treatment

Background/Aims: The short stature homeobox-containing (SHOX) gene is one of many genes that regulate longitudinal growth. The SHOX deficiency (SHOX-D) phenotype, caused by intragenic or regulatory region defects, ranges from normal stature to mesomelic skeletal dysplasia. We investigated differences in radiological anomalies between patients with SHOX-D and Turner syndrome (TS) and the effect of 2 years of growth hormone (GH) treatment on these anomalies. Methods: Left hand/wrist, forearm and lower leg radiographs were assessed at baseline and after 2 years in children with genetically confirmed SHOX-D (GH-treated and untreated groups) and TS (GH-treated) in a randomised, controlled, multinational study. Results: Radiological anomalies of hand, wrist and forearm were common in SHOX-D and TS. Radial bowing appeared more prevalent in SHOX-D, while lower leg anomalies were more common in TS. There were no significant differences in radiological findings between GH-treated and untreated patients with SHOX-D after 2 years. Conclusion: GH treatment had no systematic effect on skeletal findings in SHOX-D, based on limited radiological differences between the GH-treated and untreated groups at 2 years. Bone age radiographs allow assessment of radiological signs indicating a potential diagnosis of SHOX-D and may lead to earlier genetic confirmation and initiation of GH therapy.

Konjenital el redüksiyon defekti ile uterus anomalisinin birlikteliği

Objective: Fetal hand anomalies can be overlooked in ultrasonographic examinations. In our report, we aim to present the case of hand reduction defect in a patient with uterine anomaly that we diagnosed during antenatal follow-up with the use of 2D and 3D ultrasound examinations. Case: Genetic consultation was provided to a patient who had absence of hand in one extremity during the ultrasound control performed for triple test while nothing was detected in the ultrasound for double test screening. After the amniocentesis, the karyotype of fetus was found as normal (46 --). No other anomaly was observed in perinatology consultation, anomaly screening and fetal echocardiography. Remaining gestational period of the patient was free of problem and a single 3300 g fetus was delivered by cesarean section through breech presentation and the pictures of the hand were taken with the permission of the family. Conclusion: Congenital hand reduction defects may occur together with uterine anomalies. Such anomalies can be diagnosed easily during ultrasonographic examinations in early weeks of gestation, and therefore they should be a part of early anomaly screening procedures.

Clinical Analysis of 113 Patients With Poland Syndrome

Poland syndrome is a rare congenital anomaly characterized by the partial or complete absence of pectoral muscles, varying thoracic deformities, and hand anomalies. To date, many variants of this syndrome and its accompanying anomalies have been reported. In our clinic, 113 patients were diagnosed with Poland syndrome between 1990 and 2014. A latissimus dorsi muscle transfer was performed on 6 of these patients. Out of 113 patients, 63 (55.7%) were diagnosed with the syndrome on the right side, 42 (37.1%) were diagnosed on the left side, and 8 (7%) had a bilateral diagnosis. The partial or complete absence of the pectoralis major muscle was detected in all patients. Although 81 (71.6%) patients had a complete absence of the pectoralis major muscle, 32 (28.3%) were lacking only the sternocostal head of the muscle. In the analyzed cases, Poland syndrome was also found to be accompanied by specific anomalies. The most common anomaly accompanying Poland syndrome in these patients was Sprengel deformity, seen in 18 patients. Symmetry and stabilization of the chest wall were performed in 6 patients through transfer of the latissimus dorsi muscle. Poland syndrome is a rare congenital anomaly, which has several variants and accompanying anomalies. The absence of several muscles in addition to the pectoral muscle can be seen in patients with Poland syndrome. Sprengel deformity is the most common accompanying anomaly. Several surgical procedures have been reported for the syndrome; for example, transposing the latissimus dorsi muscle is an effective procedure in terms of stabilizing the chest wall and providing optimum symmetric body appearance.

Radiological imaging of congenital hand anomalies--a 6-year single-centre experience and what the hand surgeons want to know.

Congenital hand anomalies present a rare but important physical and emotional challenge for children and parents. Radiological imaging is important for accurate diagnosis, to aid decision making and to monitor changes in the growing hand. The goal of any treatment is to help the child achieve his/her maximum potential, to provide a useful hand with attention to cosmesis. We investigated the range of congenital hand anomalies imaged in a tertiary referral centre. We examined the timing of imaging and the key clinical questions. The radiology imaging system was searched retrospectively for radiographs of congenital hand anomalies over a 6-year period. The images were reviewed and patient demographics, diagnosis and other imaging recorded. Over 6 years, 85 patients had imaging. Twenty-three patients had bilateral problems and 11 had recognised syndromes. The most common abnormalities imaged were duplicated thumbs (28 %), followed by syndactyly (18 %). Children were first imaged as early as 1 day old, with the median age of initial imaging 12 months. Thumb duplication and syndactyly are the most common conditions for which radiographs are requested at our hospital, although overall syndactyly is considered the most common congenital hand anomaly. For a variety of reasons, children are often imaged very early, before review by the Specialist in Children's Hand Surgery (despite surgery being unlikely before 1 year of age.) We discuss the classification systems and specific issues that hand surgeons want to know from the radiologists.

Medical tactic in hand polydactyly in children

Untimely correction of anomalies of fingers and hands or inefficiently performed reconstructive operations may affect the processes of adaptation of children to life. Objective: To improve outcomes in children with polydactyly by optimizing the methods of surgical correction of congenital hand pathology. Methods: During the period from 2000 to 2012 in 118 patients (70 boys, 48 girls, age to 6 years) with polydactyly there were performed 141 operations on 136 hands. There were 68 children with radial form of polydactyly, 17 with ulnar form, and 3 with central one. For establishment of the nature of the pathology examination with using of radiological, CT, and ultrasound dopplerography mapping was done. Results: In the case of the main finger deformity after removal of additional finger we performed corrective osteotomies, modeling resections of articular surfaces, and restored capsular-ligamentous apparatus. In cases of ulnar polydactyly with thickening of V metacarpal bone on the wide head of which there are two claw like little fingers we removed less developed one, cut off the abductor digiti minimi, restored lateral metacarpophalangeal ligament, fixed the muscle to the proximal phalanx, angular deformity of the V finger we eliminated by wedge osteotomy with K-wire fixation. In cases of central polydactyly after removal of extra finger we used created from a remote segment reserve of skin for closing the skin defect on lateral surfaces of the fingers with simultaneous correction of axial deformities. Long-term outcomes were followed up during the period of 1 to 10 years in 78 children: good results were obtained in 44 cases, satisfactory — in 27, and unsatisfactory — in 7 cases. Errors and complications: deviation of the main finger, nonunion of bone surfaces, scar deformities, limitation of movement. Conclusions: While choosing the method of surgery and duration of its execution one should establish the primary and the secondary fingers in cases of radial polydactyly. Zigzag incisions, rational skin, bone and tendon plasty allow to prevent the formation of scar contractures and secondary deformities of fingers and contribute to the restoration of the hand function.