Variant type and position predict two distinct limb phenotypes in patients with GLI3-mediated polydactyly syndromes

Introduction: Pathogenic DNA variants in the GLI-Kruppel family member 3 (GLI3) gene are known to cause multiple syndromes: for example, Greig syndrome, preaxial polydactyly-Type 4 (PPD4) and Pallister-Hall syndrome. Out of these, Pallister-Hall is a different entity, but the distinction between Greig syndrome and PPD4 is less evident. Using latent class analysis (LCA), our study aimed to investigate the correlation between reported limb anomalies and the reported GLI3 variants in these GLI3-mediated polydactyly syndromes. We identified two subclasses of limb anomalies that relate to the underlying variant. Methods: Both local and published cases were included for analysis. The presence of individual limb phenotypes was dichotomised and an exploratory LCA was performed. Distribution of phenotypes and genotypes over the classes were explored and subsequently the key predictors of latent class membership were correlated to the different clustered genotypes. Results: 297 cases were identified with 127 different variants in the GLI3 gene. A two-class model was fitted revealing two subgroups of patients with anterior versus posterior anomalies. Posterior anomalies were observed in cases with truncating variants in the activator domain (postaxial polydactyly; hand, OR: 12.7; foot, OR: 33.9). Multivariate analysis supports these results (Beta: 1.467, p=0.013 and Beta: 2.548, p<0.001, respectively). Corpus callosum agenesis was significantly correlated to these variants (OR: 8.8, p<0.001). Conclusion: There are two distinct phenotypes within the GLI3-mediated polydactyly population: Anteriorly and posteriorly orientated. Variants that likely produce haploinsufficiency are associated with anterior phenotypes. Posterior phenotypes are associated with truncating variants in the activator domain. Patients with these truncating variants have a greater risk for corpus callosum anomalies

The unsolved problem of radial longitudinal dysplasia: how can we reliably prevent recurrence, preserve growth and optimize function?

Congenital radial longitudinal dysplasia remains an ‘unsolved problem' in hand surgery. The challenges presented by the skeletal deficiency of the distal radius and soft tissue dysplasia of the severe radial longitudinal deficiency have been addressed by a number of techniques that aim to stabilize the position of the hand relative to the forearm and optimize forearm growth and hand function. Analysis of hand function and position in these children is difficult because of the abnormal ‘wrist' mechanics, and the published results of the techniques used to date often lack a standardized approach and importantly the perception of function from the patient's perspective. The existing data is reviewed and compared with the results of cohorts from two major congenital upper limb centres. Soft tissue distraction prior to radialization or centralization may offer benefit in ulnar growth and forearm length but there is a need for further research into the long-term functional outcomes of the various techniques available to determine the optimal choice for these children

Spontaneous breast enlargement following liposuction of the abdominal wall: Does a link exist?

Background: A retrospective study was undertaken to determine the specific incidence of breast enlargement following liposuction of the abdomen (alone or in combination with the flanks), and to compare its effect with a control group of patients who had undergone abdominoplasty only and, where possible, identify corresponding variables. Methods: Forty-eight of 84 patients (57 percent) who had undergone a tumescent liposuction procedure of at least the abdominal wall and/or flanks and 53 of 104 patients (51 percent) who had undergone abdominoplasty met the entry criteria and formed the study group and the control group, respectively. The medical records were reviewed retrospectively, patient interviews were conducted and, where possible, the patients were examined. Patients who had undergone previous breast or abdominal wall surgery or who had a history of or were breast-feeding at the time of the study were excluded. Results: In the liposuction group, 23 of the 48 patients (48 percent) reported an increase in their breast size postoperatively. This could objectively be confirmed (by an actual increase of at least one bra cup size) in 19 patients (40 percent). Nine of 19 responders (47 percent) presented with a weight gain of as little as 4 percent of body mass index following liposuction, whereas this was observed in only one of 29 of the nonresponder group (3 percent) (p <0.0001). In the abdominoplasty group, 11 patients (21 percent) claimed to have perceived an increase in breast size, which was objectively confirmed by an increase in bra cup size in six (11 percent) only. Four of the six responders (with an increased cup size) reported a weight gain from as little as 4 percent of body mass index, compared with nine of the remaining 47 patients (19 percent) comprising the nonresponder group (p <0.01). Conclusions: Liposuction of the abdominal wall and/or flanks is followed by breast enlargement in a significant number of patients (40 percent), a risk that is significantly higher when compared with patients who have undergone abdominoplasty only. Patients should be informed about the possibility and risk of breast enlargement following liposuction of the abdominal wall in particular

Lateral Versus Medial Hallux Excision in Preaxial Polydactyly of the Foot

Background: In preaxial polydactyly of the foot, the choice for excision of the lateral or medial hallux is not straightforward, in particular with proximal phalangeal (type IV) and metatarsal (type VI) duplication, because of anatomical characteristics. We evaluated whether medial or lateral hallux excision gives better outcomes in these duplication types, to help clinical decision making. Methods: Children with type IV or type VI duplication (n=14, age: 4.4-17.2 years), who were operatively treated by excision of the lateral or medial hallux, were assessed for foot function using plantar pressure measurements and clinical examination. Foot aesthetics were scored by the child, an expert, and 10 laypersons, and additional patient-reported outcome questionnaires were obtained. Outcomes were compared between lateral and medial excision, per duplication type. Results: In type IV duplication (n=11), lateral excision showed a better distribution of peak pressure between the hallux and first metatarsal with significantly lower median first metatarsal peak pressure (P =.008). Lateral excision showed more medial hallux deviation (P =.017). Foot aesthetics were not different between excision sides. In type VI duplication (n=12), lateral excision showed a 59% higher hallux peak pressure, larger medial hallux deviation (P =.004), and more reoperations. Foot aesthetics were scored significantly better after lateral excision by experts and laypersons. Conclusions: Foot function by virtue of plantar pressure was better after lateral hallux excision in type IV and after medial hallux excision in type VI duplication. Surgeons and laypersons perceived the foot as more normal after lateral excision in type VI, whereas children reported no differences. These outcomes can be used in clinical decision making. Level of Evidence: Level III, therapeutic, comparative study

Foot Function in Patients With Surgically Treated Preaxial Polydactyly of the Foot Compared With Age- and Sex-Matched Healthy Controls

Background: Treatment of preaxial foot polydactyly, a duplication of the first ray, consists of excision of an extra ray, aiming to improve shoe fitting and aesthetic appearance, while maintaining foot function. Currently, the effect of excision on foot function and foot-related patient experiences is unclear. Methods: A cross-sectional comparison between 37 children treated for preaxial foot polydactyly and 37 age- and sex-matched healthy controls was performed. Dynamic foot function was assessed using plantar pressure measurements and static foot characteristics by physical examination. Patient-reported outcomes for foot function and footwear were evaluated, using the Oxford Ankle Foot Questionnaire for Children (score, 0-100). Results: Compared with controls, patients had significantly lower median peak pressures at the hallux (148 kPa [IQR, 98-245] vs 272 kPa [IQR, 205-381], P <.001) and significantly higher peak pressures at the second metatarsal (217 kPa [IQR, 147-338] vs 166 kPa [IQR, 141-235], P =.002) and third to fifth metatarsals (214 kPa [IQR, 147-290] vs 161 kPa [IQR, 135-235], P <.001). Additionally, patients had a more medially deviated hallux, both while seated (15 degrees (IQR, 11-20) vs 12 degrees [IQR, 10-15], P =.001) and standing (20 degrees [IQR, 15-26] vs 18 degrees [IQR, 15-20], P =.001). No significant correlation between peak pressure distribution and hallux deviation was found. Patients reported minimal problems with foot function (87.5 [IQR, 64.6-100]), but distinct problems with footwear use (50.0 [IQR, 25.0-100]). Conclusion: Patients with surgically treated preaxial foot polydactyly had a substantially altered plantar pressure distribution with more lateral foot progression than healthy controls. Although an increased hallux deviation was not related to altered foot function, it seemed to be the reason for the patient-perceived problems with footwear. Level of Evidence: Level III, comparative series

Preaxial polydactyly of the foot: Clinical and genetic implications for the orthopedic practice based on a literature review and 76 patients

Background and purpose — Preaxial polydactyly of the foot is a rare malformation and clinicians are often unfamiliar with the associated malformations and syndromes. In order to give guidelines for diagnostics and referral to a clinical geneticist, we provide an overview of the presentation using a literature review and our own patient population. Patients and methods — The literature review was based on the Human Phenotype Ontology (HPO) project. From the HPO dataset, all phenotypes describing preaxial polydactyly were obtained and related diseases were identified and selected. An overview was generated in a heatmap, in which the phenotypic contribution of 12 anatomical groups to each disease is displayed. Clinical cases were obtained from our hospital database and were reviewed in terms of phenotype, genotype, heredity, and diagnosed syndromes. Results — From the HPO dataset, 21 diseases were related to preaxial polydactyly of the foot. The anatomical groups with the highest phenotypic contribution were lower limb, upper limb, and craniofacial. From our clinical database, we included 76 patients with 9 different diseases, of which 27 had a GLI3 mutation. Lower limb malformations (n = 55), upper limb malformations (n = 59), and craniofacial malformations (n = 32) were most frequently observed. Malformations in other anatomical groups were observed in 27 patients. Interpretation — Preaxial polydactyly of the foot often presents with other upper and lower limb malformations. In patients with isolated preaxial polydactyly of the foot, referral to a clinical geneticist is not mandatory. In patients with additional malformations, consultation with a clinical geneticist is recommended. When additional limb malformations are present, analysis of GLI3 is most feasible

Minimally Invasive Options in Dupuytren's Contracture: Aponeurotomy, Enzymes, Stretching, and Fat Grafting

Learning Objectives: After studying this article, the participant should be able to: (1) Perform needle aponeurotomy, fat grafting, Digit Widget insertion, and collagenase injection for Dupuytren's cords. (2) Describe how cords can be stretched without surgery. (3) Explain to patients the risks and benefits of these new alternatives of treatments. Summary: Surgery for Dupuytren's contracture used to be the only alternative of treatment. The past 5 years have seen the widespread adoption of minimally invasive treatments in the form of needle aponeurotomy and collagenase injection to disrupt the cords and restore range of motion. Even newer and perhaps as effective treatments such as fat grafting and mechanical stretching with the Digit Widget may also end up being important tools of treatment. The reader will be introduced to all of these modalities with text, illustration, and videos