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A 15-year-old girl with humeroradial synostosis since birth underwent a resection arthroplasty. A trapezoidal resection osteotomy of approximately 2 cm was performed at the anterior part of the bone flexure. This resulted at 18 months in an elbow arc of motion of 60°-110° and forearm pronation/supination of 40° and 60° without postoperative complications and improved disabilities of the arm, shoulder and hand and Hand 20 scores. Radiographic analysis revealed a humeroradial joint with a maintained pseudarthrosis and hinged motion at the humeroulnar joint. When performed by an experienced surgeon, resection arthroplasty corrects humeroradial synostosis, resulting in improvement in range of motion and quality of life. Level of Evidence: Level V (Therapeutic).

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CHARGE syndrome is a rare autosomal dominant syndrome characterized by multiple congenital anomalies including coloboma, heart defects, ear anomalies, and developmental delay, caused by pathogenic variants in the CHD7 gene. The discovery of the molecular basis of this syndrome increased the number of cases reported and expanded the phenotype and clinical variability. Limb anomalies are occasional clinical findings in this syndrome, present in about 30% of reported cases. The occurrence of limb anomalies in this syndrome suggests that it should be considered as part of the phenotypic spectrum. Here, we describe an individual with CHARGE syndrome presenting unilateral monodactyly.

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Introducción y objetivo: La sindactilia es la anomalía congénita más frecuente de la extremidad superior. El compromiso del primer espacio es una patología rara pero genera importante deterioro funcional, por lo que el tratamiento quirúrgico es esencial para restaurar la función de prensión del pulgar. Están descritas múltiples estrategias quirúrgicas para lograr un primer espacio adecuado (igual o mayor a 90°), que incluyen desde colgajos locales y/o zetaplastias en sindactillias incompletas, hasta el uso de colgajos libres de antebrazo o expansores tisulares para sindactilias completas, con resultados funcionales variables y posible compromiso de zonas dadoras. Centramos nuestro trabajo en el empleo de la técnica de Miura modificada, presentado 2 casos clínicos. Material y método: Describimos el uso de la técnica Miura modificada en 2 pacientes de 14 y 5 meses de edad respectivamente, para la resolución de sindactilia congénita completa del primer espacio sin asociación a mano hendida. Resultados: El seguimiento fue de 40 meses para el caso 1 y de 26 meses para el caso 2. No hubo complicaciones tempranas ni tardías ni evidencia de retracción de la cicatriz, manteniendo la amplitud del primer espacio de 90° en ambos pacientes, con buen resultado funcional y estético. Conclusiones: En nuestra experiencia, el uso de la técnica de Miura modificada es una alternativa interesante para el tratamiento de la sindactilia del primer espacio no asociada a mano hendida, con un colgajo vascularmente seguro, de diseño sencillo, con buenos resultados funcionales y mínimas consecuencias estéticas.(AU)

Background and objective: Syndactyly is the most frequent congenital anomaly of the upper limb. Syndactyly of the first space is rare, but compromises functionality, so surgical treatment is essential to restore the thumb grip function. Multiple surgical strategies to achieve adequate space (equal to or greater than 90 °) have been described. These techniques include from the use of local flaps and/or zetaplasties in incomplete syndactyly, until the use of remote flaps from the forearm and tissue expanders if it is a completely absent space, with variable functional results and/or involvement of donor areas. This paper focus on the use of modified Miura technique and presents 2 clinical cases. Methods: The use of modified Miura technique in 2 patients, 14 and 5 months old respectively, is described in the resolution of complete congenital syndactyly of the first space not associated with a cleft hand,Results: Follow-up was 40 months for case 1 and 26 months for case 2. There were no early or late complications or evidence of scar retraction, maintaining the width of the first 90° space in both patients, with good functional and aesthetic results at long term follow up. Conclusions: In our experience, the use of the modified Miura technique is an interesting alternative for the treatment of first space syndactyly not associated with cleft hand, with a vascularly safe flap, of simple design, with good functional results and minimal aesthetic consequences.(AU)

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Las deformidades de los dedos son alteraciones frecuentes y en ocasiones se asocian a camptodactilia. Estas pueden ser congénitas o adquiridas, estar asociadas a teratógenos durante la etapa prenatal o determinado por un gen heredado que provoque este defecto y manifestarse de forma aislada o en varios miembros de una misma familia, segregándose con un patrón de herencia autosómico dominante. Se presenta una familia con tres miembros afectados a partir de una progenitora con el defecto en los dedos de las manos y los pies, que tiene dos descendientes con las mismas deformidades, sin otras alteraciones. Se considera un defecto congénito con implicación estética, en la movilidad de todos los dedos en alguna medida. Resulta necesario el seguimiento multidisciplinario, en conjunto ortopédicos, psicólogos y genetista clínico, para brindar un adecuado asesoramiento genético a la familia, informar el posible tratamiento quirúrgico y la rehabilitación oportuna para elevar la calidad de vida de estos afectados.

Finger deformities are frequent alterations and are sometimes associated with camptodactyly. These can be congenital or acquired, and may be associated with teratogens during prenatal stage or determined by an inherited gene that causes this defect, as well as appear in isolation or in several members of the same family, segregating with an autosomal dominant inheritance pattern. We present a family with three affected members from a mother with a defect in fingers and toes, who has two descendants with the same deformities, without other alterations. It is considered a congenital defect with aesthetic implications, and repercussions, to some extent, on the mobility of all fingers. Multidisciplinary follow-up is necessary, together with orthopedics, psychologists, and clinical geneticists, to provide adequate genetic counseling to the family, inform possible surgical treatment, and timely rehabilitation to improve the quality of life of those affected subjects.

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Polymelia is an extremely rare congenital anomaly where an individual is born with an abnormally developed extra or supernumerary limb which is generally shrunken and functionless. A case of thoracomelia (a type of polymelia) was observed macroscopically and confirmed radiologically in 1.5 years old boy born in Nepal with an abnormal supernumerary upper limb attached to his back in the thoracic region. The limb was successfully amputated, and the boy had a favorable outcome after surgical treatment, without any adverse effects or impairment. Understanding the embryogenesis of thoracomelia is essential for unraveling the complex mechanisms underlying this condition and potentially aiding in early diagnosis and intervention. This case report and review aims to shed light on the intricate processes governing forelimb formation and their perturbations leading to thoracomelia.

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BACKGROUND: Orthopedic technical care plays a crucial role in improving function and mobility for patients undergoing limb lengthening and reconstruction. The treatment strategy is based on a precise classification of the defect, taking into account factors such as joint instability, muscle pathology and limb length discrepancy. CHOICE OF AIDS: The selection of orthopedic aids depends on the specific deformity, its classification and the individual needs of the patient. Through interdisciplinary decision-making and customized adaptations of prostheses and orthoses, optimal function and aesthetically pleasing outcomes can be achieved. The utilization of custom-made technical components, such as traction devices combined with elastic liners, is essential for long-term treatment success and can support surgical interventions. The treating physician's expertise is crucial in selecting the appropriate orthopedic technical device following limb lengthening and reconstruction.

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(1) Background: Lower Limb deformities include many conditions where pain and physical limitations negatively impact the health-related quality of life (HRQL) of children. The ideal way to assess this impact is by using a Patient Reported Outcome Measure (PROM). Such a condition-specific PROM is under development, called LIMB-Q Kids. This study aimed to perform a translation and cultural adaption (TCA) of the LIMB-Q Kids for use in Danish-speaking children. (2) Methods: TCA guidelines established by the World Health Organization (WHO) and the Professional Society for Health Economics and Outcomes Research (ISPOR) were followed. This process consisted of two independent forward translations, a reconciliation meeting, a backward translation with an assessment, an expert meeting, cognitive interviews with patients, editing based on the interviews, and proofreading. (3) Results: The TCA process contributed to the Danish version of LIMB-Q Kids. The reconciliation meeting resulted in a reconciled Danish version. The revision of the backward translation led to 16 corrections, and after the expert panel meeting, 26 changes were made. Twelve cognitive interviews led to nine changes, which were validated by two further interviews. Proofreading led to no further comments. (4) Conclusions: The TCA process led to a linguistically validated and culturally adapted Danish version of LIMB-Q Kids. This version is being used in the international field test study.

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The correction of valgus leg malalignment in children using implant-mediated growth guidance is widely used and effective. Despite the minimal invasive character of the procedure, a relevant number of patients sustain prolonged pain and limited mobility after temporary hemiepiphysiodesis. Our aim was to investigate implant-associated risk factors (such as implant position and screw angulation), surgical- or anesthesia-related risk factors (such as type of anesthesia, use, and duration), and pressure of tourniquet or duration of surgery for these complications. Thirty-four skeletally immature patients with idiopathic valgus deformities undergoing hemiepiphysiodesis plating from October 2018-July 2022 were enrolled in this retrospective study. Participants were divided into groups with and without prolonged complications (persistent pain, limited mobility of the operated knee between five weeks and six months) after surgery. Twenty-two patients (65%) had no notable complications, while twelve patients (35%) had prolonged complications. Both groups differed significantly in plate position relative to physis (p = 0.049). In addition, both groups showed significant differences in the distribution of implant location (p = 0.016). Group 1 had a shorter duration of surgery than group 2 (32 min vs. 38 min, p = 0.032) and a lower tourniquet pressure (250 mmHg vs. 270 mmHg, p = 0.019). In conclusion, simultaneous plate implantation at the femur and tibia and metaphyseal plate positioning resulted in prolonged pain and a delay of function. In addition, the amplitude of tourniquet pressure or duration of surgery could play a factor.

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Introduction Some children with motor disabilities show low cognitive levels. However, the influence of motor disabilities on children's intelligence remains to be fully elucidated. This study aimed to clarify the intellectual characteristics of children with upper limb deficiencies and the influence of upper limb impairments on intelligence. Methods The participants were 10 children from four to six years of age with congenital unilateral transradial or transcarpal limb deficiencies who received prosthetic interventions. The children's intelligence and adaptive behaviors, including motor skills, were examined using the Wechsler Preschool and Primary Scale of Intelligence and the Vineland Adaptive Behavior Scale, respectively. Results There were no significant characteristics or discrepancies in cognitive level in children with upper limb deficiencies. The Adaptive Behavior Composite Score of the Vineland Adaptive Behavior Scale was significantly positively correlated with the Full-Scale Intelligence Quotient of the Wechsler Preschool and Primary Scale of Intelligence. Conclusions The children with congenital limb deficiencies showed average cognitive levels. Expansion of adaptive behaviors, including appropriate complementation of disabilities, may promote intellectual development in children with motor disabilities.

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BACKGROUND: Oral clefts and ectrodactyly are common, heterogeneous birth defects. We performed whole-exome sequencing (WES) analysis in a Syrian family. The proband presented with both orofacial clefting and ectrodactyly but not ectodermal dysplasia as typically seen in ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome-3. A paternal uncle with only an oral cleft was deceased and unavailable for analysis. METHODS: Variant annotation, Mendelian inconsistencies, and novel variants in known cleft genes were examined. Candidate variants were validated using Sanger sequencing, and pathogenicity assessed by knocking out the tp63 gene in zebrafish to evaluate its role during zebrafish development. RESULTS: Twenty-eight candidate de novo events were identified, one of which is in a known oral cleft and ectrodactyly gene, TP63 (c.956G > T, p.Arg319Leu), and confirmed by Sanger sequencing. CONCLUSION: TP63 mutations are associated with multiple autosomal dominant orofacial clefting and limb malformation disorders. The p.Arg319Leu mutation seen in this patient is de novo but also novel. Two known mutations in the same codon (c.956G > A, p.(Arg319His; rs121908839, c.955C > T), p.Arg319Cys) cause ectrodactyly, providing evidence that mutating this codon is deleterious. While this TP63 mutation is the best candidate for the patient's clinical presentation, whether it is responsible for the entire phenotype is unclear. Generation and characterization of tp63 knockout zebrafish showed necrosis and rupture of the head at 3 days post-fertilization (dpf). The embryonic phenotype could not be rescued by injection of zebrafish or human messenger RNA (mRNA). Further functional analysis is needed to determine what proportion of the phenotype is due to this mutation.

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Collagen VI exerts several functions in the tissues in which it is expressed, including mechanical roles, cytoprotective functions with the inhibition of apoptosis and oxidative damage, and the promotion of tumor growth and progression by the regulation of cell differentiation and autophagic mechanisms. Mutations in the genes encoding collagen VI main chains, COL6A1, COL6A2 and COL6A3, are responsible for a spectrum of congenital muscular disorders, namely Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and myosclerosis myopathy (MM), which show a variable combination of muscle wasting and weakness, joint contractures, distal laxity, and respiratory compromise. No effective therapeutic strategy is available so far for these diseases; moreover, the effects of collagen VI mutations on other tissues is poorly investigated. The aim of this review is to outline the role of collagen VI in the musculoskeletal system and to give an update about the tissue-specific functions revealed by studies on animal models and from patients' derived samples in order to fill the knowledge gap between scientists and the clinicians who daily manage patients affected by collagen VI-related myopathies.

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BACKGROUND: Malalignments of the lower extremity are common reasons for orthopedic consultation because it may lead to osteoarthritis in adulthood. An accurate and reliable radiological assessment of lower limb alignment in children and adolescents is essential for clinical decision-making on treatment of limb deformities and for regular control after a surgical intervention. OBJECTIVE: First, does the analysis of full-length standing anteroposterior radiographs show a good intra- and interobserver reliability? Second, which parameter is most susceptible to observer-dependent errors? Third, what is the Standard Error of Measurement (SEM95%) of the absolute femoral and tibial length? METHODS: Two observers evaluated digital radiographs of 144 legs from 36 children and adolescents with pathological valgus alignment before a temporary hemiepiphysiodesis and before implant removal. Parameters included Mechanical Femorotibial Angle (MFA), Mechanical Axis Deviation (MAD), mechanical Lateral Distal Femoral Angle (mLDFA), mechanical Medial Proximal Tibial Angle (mMPTA), mechanical Lateral Proximal Femoral Angle (mLPFA), mechanical Lateral Distal Tibial Angle (mLDTA), Joint Line Convergence Angle (JLCA), femur length, tibial length. Intra- and interobserver reliability (ICC2,1), SEM95% and proportional errors were calculated. RESULTS: The intra- and interobserver reliability for almost all measurements was found to be good to excellent (Intra-ICC2,1: 0.849-0.999; Inter-ICC2,1: 0.864-0.996). The SEM95% of both observers was found to be ± 1.39° (MFA), ± 3.31 mm (MAD), ± 1.06° (mLDFA) and ± 1.29° (mMPTA). The proportional error of MAD and MFA is comparable (47.29% vs. 46.33%). The relevant knee joint surface angles show a lower proportional error for mLDFA (42.40%) than for mMPTA (51.60%). JLCA has a proportional error of 138%. Furthermore, the SEM95% for the absolute values of the femoral and tibial length was 4.53 mm for the femur and 3.12 mm for the tibia. CONCLUSIONS: In conclusion, a precise malalignment measurement and the knowledge about SEM95% of the respective parameters are crucial for correct surgical or nonsurgical treatment. The susceptibility to error must be considered when interpreting malalignment analysis and must be considered when planning a surgical intervention. The results of the present study elucidate that MAD and MFA are equally susceptible to observer-dependent errors. This study shows good to excellent intra- and interobserver ICCs for all leg alignment parameters and joint surface angles, except for JLCA. TRIAL REGISTRATION: This study was registered with DRKS (German Clinical Trials Register) under the number DRKS00015053. LEVEL OF EVIDENCE: I, Diagnostic Study.

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BACKGROUND: Motorized lengthening nails are the treatment standard for bone lengthening of the lower limbs. However, bony changes namely osteolysis and periosteal hypertrophy have been described after certain type of magnetically driven lengthening nails. The aim of this study was to estimate the proportion rate of radiological bone abnormalities of Fitbone TAA femoral or tibial lengthening nails with a minimum follow-up time of 1 year. HYPOTHESIS: The bone surrounding the telescopic junction of Fitbone lengthening nails does not exhibit osteolysis or periosteal reactions. The bone surrounding the locking screws exhibits cortical hypertrophy. PATIENTS AND METHODS: Single-centre retrospective case series of patients treated with a Fitbone nails with a minimum follow-up of 1 year after implantation. Standard orthogonal radiographs were obtained postoperatively, weekly during the distraction phase, and then monthly for 6 months, and before removal of the equipment. We looked for bone abnormalities at the telescoping junction of the nail and at the locking screws before removal. RESULTS: In total, 101 patients (58 males, 43 females) with a mean age of 21 years (range: 11.8-53.5) had 128 (101 femoral and 27 tibial) limb lengthening nails implanted between 2010 and 2021. The mean follow-up period was 925 days (range: 371-3587). The mean lengthening was 4.7cm (range: 1.5-8.0). No bones exhibited focal osteolysis or periosteal reactions at the telescopic junction of the lengthening nail. Cortical hypertrophy at the locking screws was observed in significantly more Fitbone nails than previously reported, i.e., 101/128 (79%). DISCUSSION: Neither focal osteolysis, nor periosteal reactions were observed at the bone surrounding the telescopic junction of 128 Fitbone lengthening nails. Cortical hypertrophy around the single diaphyseal locking screw was observed in 101/128 (79%) of the cases. These absences of osteolytic changes after long term observation are reassuring for both surgeons and patients alike. LEVEL OF EVIDENCE: IV.

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The Adams-Oliver syndrome is a rare congenital disorder characterized by aplasia cutis congenita of the scalp, terminal transverse limb defects, and congenital telangiectatic cutis marmorata. It can occur through different inheritance patterns: autosomal dominant, autosomal recessive, or de novo dominant mutations. Although the Adams-Oliver syndrome is a rare disease, it is essential to know its clinical characteristics and inheritance patterns, to establish a correct diagnosis and its possible complications during follow-up. In the present study, we describe the case of an adolescent with Adams-Oliver syndrome with an autosomal dominant inheritance pattern, pulmonary hypertension and plastic bronchitis, and several compromised family members.

El síndrome de Adams-Oliver es un trastorno congénito raro, caracterizado por aplasia cutis congénita en el cuero cabelludo, defectos terminales transversales de las extremidades y piel marmorata telangiectásica congénita. Este puede presentarse debido a diferentes patrones de herencia de tipo autosómico dominante o autosómico recesivo, o por mutaciones dominantes de novo. Aunque el síndrome de Adams-Oliver es una enfermedad poco frecuente, es importante conocer sus características clínicas y patrones de herencia, para así establecer un correcto diagnóstico y sus posibles complicaciones durante el seguimiento. En el presente estudio, se describe el caso de una adolescente con síndrome de Adams-Oliver con patrón de herencia autosómica dominante, hipertensión pulmonar y bronquitis plástica. Había varios miembros de su familia con el mismo compromiso.

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El síndrome de Adams-Oliver es un trastorno congénito raro, caracterizado por aplasia cutis congénita en el cuero cabelludo, defectos terminales transversales de las extremidades y piel marmorata telangiectásica congénita. Este puede presentarse debido a diferentes patrones de herencia de tipo autosómico dominante o autosómico recesivo, o por mutaciones dominantes de novo. Aunque el síndrome de Adams-Oliver es una enfermedad poco frecuente, es importante conocer sus características clínicas y patrones de herencia, para así establecer un correcto diagnóstico y sus posibles complicaciones durante el seguimiento. En el presente estudio, se describe el caso de una adolescente con síndrome de Adams-Oliver con patrón de herencia autosómica dominante, hipertensión pulmonar y bronquitis plástica. Había varios miembros de su familia con el mismo compromiso

The Adams-Oliver syndrome is a rare congenital disorder characterized by aplasia cutis congenita of the scalp, terminal transverse limb defects, and congenital telangiectatic cutis marmorata. It can occur through different inheritance patterns: autosomal dominant, autosomal recessive, or de novo dominant mutations. Although the Adams-Oliver syndrome is a rare disease, it is essential to know its clinical characteristics and inheritance patterns, to establish a correct diagnosis and its possible complications during follow-up. In the present study, we describe the case of an adolescent with Adams-Oliver syndrome with an autosomal dominant inheritance pattern, pulmonary hypertension and plastic bronchitis, and several compromised family members.

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(1) Purpose: Lower limb deformities can have a severe impact on health-related quality of life (HRQL). LIMB-Q Kids is a new patient-reported outcome measure (PROM) aiming to elucidate the experience of 8-18-year-old patients before, during and after treatment, and to measure the different aspects of HRQL. The aim of this study was to translate and culturally adapt LIMB-Q Kids to German. (2) Methods: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines were followed. Three forward translations, a backward translation, an expert panel meeting with eight participants, and twenty cognitive debriefing interviews led to the final German version of LIMB-Q Kids. (3) Results: In the forward translations, 4/159 items were difficult to translate, and 2/159 items in the backward translation differed from the original English version. Cognitive debriefing interviews with 20 patients identified 7/159 items that were difficult to comprehend/answer, and 2 of these items were changed. (4) Conclusions: Lower limb deformities can have a great impact on children, and it is important to measure and consider the impact on HRQL. In order to be able to use PROMs in different countries, conceptually equivalent translations and cultural adaptations should be performed in order to ensure comprehensibility. The final German version of LIMB-Q Kids is ready for use in an international field test.

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PURPOSE: To establish the content validity of LIMB-Q Kids, a new patient-reported outcome measure (PROM) for children with lower limb deformities. This study focused on three key components of content validity, i.e., comprehension, comprehensiveness, and relevance. METHODS: Cognitive debriefing interviews (CDIs) with children with lower limb deformities were performed, and expert input from parents and clinicians directly involved in the care of children with lower limb deformities was obtained. CDIs were conducted with children from sites in Australia, Canada, and the USA. All interviews were recorded and transcribed verbatim. Analyses were conducted using the reparative approach, which involved close examination of the transcribed interviews and summarising edits after each interview. RESULTS: Forty patients, experts, and parents reviewed LIMB-Q Kids and provided feedback. At the start, LIMB-Q Kids had 10 scales and 124 total items. Five rounds of input was obtained from children, parents, and experts. Overall, 37 new items were added. Thirty-three of the new items were included to measure symptoms experienced in different parts of the legs. Final version of LIMB-Q Kids had 11 scales and 159 items. CONCLUSION: This study established content validity of the LIMB-Q Kids, a new PROM for children with lower limb deformities. An international field-test study is underway. Translation and cultural adaptation are underway for sites where English is not the first language. Scoring algorithms will be developed, following which the scale could be used to inform clinical practice and research.

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The anomaly P is a mass morphological anomaly reported in some water frog populations across Europe. It was found that polydactyly is only a mild attenuated form of heavy cases of the anomaly P syndrome, which have strong deformations of the hindlimbs and, partly, forelimbs. It was shown that the anomaly P is caused by the trematode Strigea robusta and this syndrome can be considered as a special case of strigeosis in amphibians. The anomaly P for a long time considered to be specific for water frogs of the genus Pelophylax. Herein, we describe polydactyly and heavy forms of the anomaly P syndrome in toads of the genera Bufo and Bufotes, as a result of exposure to S. robusta cercariae. A total of 150 tadpoles of Bufo bufo, 60 tadpoles of Bufotes viridis, and 60 tadpoles of Bufotes baturae were divided into five experimental and four control groups (30 tadpoles in each group). All anomalies in the toads were similar to those observed in water frogs. The survival of tadpoles in the experimental groups was 76%. The anomaly P was observed in 57.9% of toad tadpoles (51.8% of mild forms and 6.1% of heavy forms). The occurrence of the anomaly P varied among groups from 19% to 78%. Heavy forms of the anomaly P were found in all experimental groups. We described rare asymmetrical cases of the anomaly P. According to severe modification of limb morphology, we supposed changes of gonadal morphology (any modifications of the germ and somatic cells). The gonadal development of infected tadpoles was however the same as in uninfected toad tadpoles, and heterochromatin distribution within gonocytes had no differences as well. It seems like the parasite doesn't have any effect on the gonadal development of the toads. The lack of heavy forms in natural populations of toads, as well as a development of gonads were discussed.

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In an attempt to generate g.A746G substitution in the BMPR-IB gene, we unexpectedly obtained BMPR-IB homozygous knockout piglets ( BMPR-IB -/-) and heterogeneous knockout piglets with one copy of the A746G mutation ( BMPR-IB -/746G) via CRISPR/Cas9 editing. Polymerase chain reaction (PCR) and sequencing revealed complex genomic rearrangements in the target region. All BMPR-IB-disrupted piglets showed an inability to stand and walk normally. Both BMPR-IB -/- and BMPR-IB -/746G piglets exhibited severe skeletal dysplasia characterized by distorted and truncated forearms (ulna, radius) and disordered carpal, metacarpal, and phalangeal bones in the forelimbs. The piglets displayed more severe deformities in the hindlimbs by visual inspection, including fibular hemimelia, enlarged tarsal bone, and disordered toe joint bones. Limb deformities were more profound in BMPR-IB -/- piglets than in the BMPR-IB -/746G piglets. Proteomic analysis identified 139 differentially expressed proteins (DEPs) in the hindlimb fibula of BMPR -IB -/746G piglets compared to the wild-type (WT) controls. Most DEPs are involved in skeletal or embryonic development and/or the TGF-ß pathway and tumor progression. Gene Ontology (GO) and protein domain enrichment analysis suggested alterations in these processes. Of the top 50 DEPs, a large proportion, e.g., C1QA, MYO1H, SRSF1, P3H1, GJA1, TCOF1, RBM10, SPP2, MMP13, and PHAX, were significantly associated with skeletal development. Our study provides novel findings on the role of BMPR-IB in mammalian limb development.

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BACKGROUND: Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is a rare type of congenital limb deformity, and most studies focus on the genetics. Case reports of the sonographic characteristics of TPT-PS during pregnancy are rare. CASE SUMMARY: A 30-year-old woman (G3P1) who had pregnancies with TPT-PS fetuses is presented. The possibility of TPT-PS was shown by ultrasound performed at the 19th wk of pregnancy, featuring hands with six metacarpals, an extra digit at the 5th finger side, and an abnormally widened thumb. Whole-exome sequencing was subsequently conducted. The results showed that exons 1-17 of the LMBR1 gene had a heterozygous duplication, with a length of approximately 253 kb. CONCLUSION: We suggest prenatal ultrasound examination combined with genetic testing to diagnose TPT-PS accurately and to help clinicians and patients make decisions.