TBX5 variants and cardiac phenotype: A systematic review of the literature and a novel variant.

T-Box Transcription Factor 5 (TBX5) variants are associated with Holt-Oram syndrome. Holt-Oram syndrome display phenotypic variability, regarding upper limb defects, congenital heart defects, and arrhythmias. To investigate the genotype-phenotype relationship between TBX5 variants and cardiac disease, we performed a systematic review of the literature. Through the systematic review we identified 108 variants in TBX5 associated with a cardiac phenotype in 277 patients. Arrhythmias were more frequent in patients with a missense variant (48% vs 30%, p = 0.009) and upper limb abnormalities were more frequent in patients with protein-truncating variants (85% vs 64%, p = 0.0008). We found clustering of missense variants in the T-box domain. Furthermore, we present a family with atrial septal defects. By whole exome sequencing, we identified a novel missense variant p.Phe232Leu in TBX5. The cardiac phenotype included atrial septal defect, arrhythmias, heart failure, and dilated cardiomyopathy. Clinical examination revealed subtle upper limb abnormalities. Thus, the family corresponds to the diagnostic criteria of Holt-Oram syndrome. We provide an overview of cardiac phenotypes associated with TBX5 variants and show an increased risk of arrhythmias associated to missense variants compared to protein-truncating variants. We report a novel missense variant in TBX5 in a family with an atypical Holt-Oram syndrome phenotype.

Tarsal Tunnel Syndrome Associated With a Bipartite Talus.

BACKGROUND: Talus bipartitus is a rare skeletal anomaly that may be mistaken for an os trigonum, a relatively common accessory ossicle found posterior to the talus. Both are believed to be formed similarly with the failed fusion of the talus with a second ossification center. Os trigonum is often diagnosed incidentally or found on radiographs obtained in symptomatic patients with signs of os trigonum syndrome, which presents with posterolateral ankle pain. A bipartite talus may also present with similar symptoms but may be differentiated through its articular involvement. CASE: In this article, we describe the rare presentation of tarsal tunnel syndrome in a patient caused by a bipartite talus. The patient underwent surgical decompression with the removal of the posterior fragment. CONCLUSION: A bipartite talus is a rare entity that may be mistaken for an os trigonum, a common accessory ossicle. In this article, we describe an outcome of a bipartite talus fragment removal due to tarsal tunnel syndrome and illustrate a rare pathological consequence of a bipartite talus. We further highlight the importance of early surgical management in patients presenting with an identifiable structure contributing to tibial nerve compression.

Holt-Oram syndrome.

BACKGROUND: Holt-Oram syndrome (HOS) is a rare genetic illness, which concerns disturbances in the appearance of the upper limbs, congenital heart malformations, and cardiac conduction diseases. HOS usually requires the implantation of a pacemaker, because of cardiac conduction disturbances. CASE REPORT: We present the case of a patient with HOS qualified for pacemaker implantation due to overt bradycardia. To prevent the development of heart failure in the future, the His-bundle pacing technique was used. The implantation was successful. In the control, after one year, the man remains in good condition. The pacing was over 90%, and the left ventricular ejection fraction (LVEF) was stable (60%). CONCLUSIONS: So far, there are no reports on which methods of stimulation are required when it comes to patients with HOS. His-bundle pacing technique is a new type of physiological pacing, which can avoid heart failure.

Prevalence and a correlation analysis of discoid meniscus and femoral trochlear dysplasia.

BACKGROUND: Discoid meniscus (DM) and femoral trochlear dysplasia (FTD) are common knee disorders. Both as congenital malformation, whether there is a connection between them is unclear and the research on their prevalence in the general population is inadequate. This study aimed to investigate the prevalence of FTD and DM in the general population through a large sample size, and to explore the relationship between them. STUDY DESIGN: Retrospective study. METHODS: Patients undergoing knee magnetic resonance imaging (MRI) examinations at our outpatient clinic were screened and 1003 patients were enrolled in DM group with 989 patients in non-DM (NDM) group. The type of DM and FTD was classified with Watanabe classification and Dejour's classification, respectively. The prevalence of FTD and DM in the general population and the relationship between them were evaluated. RESULTS: The prevalence of DM and FTD was 10.0% and 14.5%, respectively. The overall percentage of FTD was higher in DM group (P < 0.001). The DM group has a higher percentage of all types of FTD except type D (P < 0.05), and a higher percentage of both low- and high-grade FTD (P < 0.001). There were 633 cases of type I DM and 370 cases of type II DM. The overall percentage of FTD was not significantly different between the two types (P = 0.106). No significant difference was detected for all types of FTD except type B (P < 0.05). The Type I DM group has a significant higher percentage of high-grade FTD than Type II group (P < 0.05). CONCLUSION: Patients with a DM are more likely to have FTD regardless of the type of DM, while those with a type I DM are more prone to have a high grade FTD.

A Biomechanical Evaluation of Casting Technique and Cast Core Size Effect.

BACKGROUNDS: The goals of this study were to (1) compare the effect of casting technique on biomechanical function with different casting materials and different cast core diameters, and (2) compare the strength of a cast based on the number of layers in relation to the core diameter. METHODS: Two standardized cylindrical cast model sizes were used to simulate forearm and short leg casts (core diameter: 60 mm, 100 mm) with 2 different casting techniques (non-smoothing vs. smoothing with lamination), utilizing 2 casting materials [fiberglass and Plaster of Paris (POP)]. Each cast was created using 3 different layers (Fiberglass: 2 to 4 layers; POP: 3 to 5 layers). Ultimate load-to-failure and flexural rigidity were analyzed through cyclic 4-point bend testing. RESULTS: The biomechanical comparison between forearm and short leg casts were significantly different regardless of the same number of layers for both casting materials and between 2 casting techniques. Increased cast thickness significantly increased the ultimate load-to-failure and bending strength. An increased core diameter size significantly decreased the cast's ultimate load-to-failure (fiberglass: 50% to 108%; POP: 10% to 93%) and bending strength (fiberglass: 17% to 35%; POP: 37% to 49%). Casting technique with smoothing with lamination technique had a negative biomechanical effect on POP and a minimal effect on fiberglass. CONCLUSION: The number of layers to apply for a cast should be based on the size of the extremity. Smoothing and lamination technique did not significantly improve the cast mechanical behavior. CLINICAL RELEVANCE: The findings of this study provide valuable evidence, analysis, and supplementary knowledge that helps guide physicians in proper casting technique.

Dislocated Extensor Mechanism in a Child With Bilateral Absent Patella Without Other Congenital Abnormalities.

CASE: A 10-year-old boy presented with bilateral absent patella and dislocation of the extensor mechanism in the left lower extremity. He underwent a lateral release and medial plication of the extensor mechanism with a Roux-Goldthwait procedure, followed by casting and bracing treatment. The patient fully recovered with a return to sports and improved active range of motion. CONCLUSION: Bilateral absent patella without other congenital anomalies is an exceedingly rare condition and can be accompanied by a dislocation of the extensor mechanism. Treatment should address functional limitations, including extensor mechanism dislocation, when present.

Single-Stage Correction of Genu Valgum Recurvatum by Distal Femoral and High Tibial Opening Wedge Osteotomies: A Case Report.

CASE: A 32-year-old woman with genu valgum recurvatum presented to clinic complaining of long-standing anterior knee pain. Radiographs demonstrated a 13° anterior tibial slope and 15° valgus malalignment. She underwent a single-stage 2-level osteotomy at the distal femur and proximal tibia to simultaneously correct genu valgum and recurvatum. This procedure achieved precise correction in both planes. At 1 year, the patient was pain-free and ambulated without restriction. CONCLUSION: This procedure should be considered among the available surgical options when treating genu valgum recurvatum because it produced excellent results for the studied patient.

Tratamiento para deformidades angulares en fémur distal con sistema LCP / Treatment of angular deformities in distal femur with LCP system

Las deformidades angulares en fémur distal son frecuentes en la consulta de ortopedia. Dependiendo del tipo de deformidad y la edad del paciente existen diferentes técnicas de corrección quirúrgica para mejorar la biomecánica de la rodilla, evitar el dolor y prevenir el daño del aparato extensor, la artrosis temprana y degeneración tardía de la articulación de la rodilla. Se realizó un estudio de tipo observacional, descriptivo, longitudinal haciendo uso del Sistema LCP como tratamiento de las deformidades angulares en Fémur Distal en pacientes con madurez esquelética alcanzada tratados en el Hospital Ortopédico Infantil durante el periodo 2012 ­ 2022. Se incluyeron un total de 17 pacientes que representan 23 rodillas; predominó el género femenino con un 76% respecto al masculino con solo 24%. La edad media de intervención quirúrgica de fue de 15±1,66 años y la edad de evaluación final de 16±1,7años. Al comparar los promedios de la evaluación radiológica pre y postoperatoria, se encontraron diferencias estadísticamente significativas <0,05 en cuanto a la corrección de la Desviación del Eje Mecánico (MAD), Ángulo Femoral Distal Lateral mecánico (LDFAm) y ángulo Femoro Tibial (AFT). El tiempo de consolidación promedio fue de 11,3±1,4 semanas, no se presentaron complicaciones inherentes al acto quirúrgico ni postoperatorias. Existen varias modalidades de tratamiento para deformidades angulares en fémur distal y el escoger una depende de la preferencia, entrenamiento del cirujano, su equipo y recursos disponibles(AU)

Angular deformities in distal femur are frequently in the orthopedic clinic, the most common of which is valgus and is characterized by an alteration of the mechanical lateral distal femoral angle (<85º). Depending of the type of deformity and the patient age at which it occurs, there are different surgical techniques correction to improve the biomechanics of the knee, avoid pain and prevent damage to the extensor apparatus, early osteoarthritis and late degeneration of the knee joint. An observational, descriptive, longitudinal study was carried out using the LCP System as a treatment for angular deformities in the Distal Femur in patients with reached skeletal maturity treated at the Hospital Ortopédico Infantil during the period 2012-2022. A total of 17 patients were included, representing 23 knees; the female predominated with 76% compared to the male with only 24%. The average age of surgical intervention was 15±1.66 years and the age of the final evaluation was 16±1.7 years. When comparing the averages of the pre and postoperative radiological evaluation, statistically significant differences <0.05 were found in terms of the correction of the Mechanical Axis Deviation (MAD), mechanical Lateral Distal Femoral Angle (LDFAm) and Femoro-Tibial angle ( AFT). The average consolidation time was 11.3 ± 1.4 weeks and there were no complications inherent to the surgical act or postoperative. There are several treatment modalities of angular deformities of the distal femur and the choice one depends of the preference and training of the surgeon, his team and the resources available(AU)

Versatilidad en la utilización del colgajo sural a flujo reverso / Versatility in the use of the sural reverse flow flap

Los defectos de cobertura cutánea en pierna y pie representan un desafío para el cirujano plástico, ya que la disponibilidad de tejidos para cobertura va disminuyendo en dirección podálica. El colgajo sural siempre ha representado una opción válida para la cobertura de elementos nobles (arterias, venas, nervios, huesos, tendones), el cual está asociado a un bajo índice de morbilidad posterior. El porcentaje de complicaciones suele ser relativamente bajo, lo cual transforma a este colgajo en una excelente opción terapéutica, ante la ausencia de opciones más avanzadas, siendo altamente reproducible y con una curva de aprendizaje relativamente baja

Skin coverage defects in the leg and foot represent a challenge for the plastic surgeon, since the availability of tissues for coverage decreases in the breech direction. The sural flap has always represented a valid option for the coverage of noble elements (arteries, veins, nerves, bones, tendons), which is associated with a low rate of posterior morbidity. The percentage of complications is usually relatively low, which makes this flap an excellent therapeutic option, in the absence of more advanced options, being highly reproducible and with a relatively low learning curve

Controlled Ankle Movement (CAM) Boot Provides Improved Outcomes With Lower Complications Than Short Leg Walking Cast in Low-energy Pediatric Lateral Ankle Injuries: A Prospective, Randomized Study.

BACKGROUND: Low-energy lateral ankle injuries (Salter-Harris 1 distal fibula, distal fibula avulsion fractures, and radiograph-negative lateral ankle injuries) are common in pediatric patients. Patient-based outcomes for the 2 treatment options, short leg walking cast (CAST) and controlled ankle motion (CAM) boot, are unknown. This study aims to determine differences between 2 treatments of low-energy lateral ankle injuries in pediatric patients. METHODS: A prospective, randomized controlled trial comparing the acute outcomes of CAST and CAM treatment for low-energy lateral ankle injuries in pediatric patients was completed. Patients were evaluated in-person at presentation and 4 weeks for ankle range of motion and Oxford foot and ankle score. A novel survey defining patient and parent satisfaction and time away from school/work was also completed. Treatment complications were documented. Patients were called at 8 weeks postinjury to determine other complications and the final time of return to sport. Mixed effects linear regression models evaluated change over time between the 2 treatment groups. RESULTS: After 60 patients were enrolled, 28 patients in the CAST group and 27 patients in the CAM group completed the study. Males comprised 51% (28), with 38 (69%) patients identifying as Hispanic. The patient's average age was 11.3±2.9 years and the average body mass index was 23.At the 4-week evaluation, the CAM group had improved range of motion, higher satisfaction scores (5.26 CAM vs. 4.25 CAST, P <0.05), similar pain scores (0.32 CAST vs. 0.41 CAM, P =0.75), and lower complications (0.54/patient CAST vs. 0.04/patient CAM, P <0.0001) than the CAST group. Female patients had improved inversion with CAM treatment than males ( P <0.05). Patients over age 12 in the CAST group had significantly decreased plantarflexion at week 4 ( P =0.002). Improvement in Oxford scores was similar between the CAST and CAM groups between the initial presentation and 4 weeks, except for increased improvement in CAM group Oxford scores for difficulty running and symptoms with walking/walking. At the 8-week evaluation, patients in the CAST group had a higher rate of continued symptoms than the CAM group (15.4% vs. 0%). CONCLUSIONS: CAM boot treatment of low-energy lateral ankle injuries in pediatric patients results in improved results and lower complications than CAST treatment. LEVEL OF EVIDENCE: Level I -randomized, controlled trial with a statistically significant difference.

Meniscal rim instability has a high prevalence and a variable location.

INTRODUCTION: Most classification systems for lateral discoid meniscus do not evaluate instability of the meniscal peripheral rim. Considerable variability in the prevalence of peripheral rim instability has been published, and it appears that instability is underestimated. The purpose of this study was: first, to evaluate the prevalence of peripheral rim instability and its location in the symptomatic lateral discoid meniscus, and second, to investigate if patient age or type of discoid meniscus are possible risk factors for instability. METHODS: A cohort of 78 knees that underwent operative treatment due to symptomatic discoid lateral meniscus was analyzed retrospectively for the rate and location of peripheral rim instability. RESULTS: Out of the 78 knees, 57.7% (45) had a complete and 42.3% (33) had an incomplete lateral meniscus. The prevalence of peripheral rim instability in symptomatic lateral discoid menisci was 51.3%, and with 32.5%, the anterior attachment was most commonly affected, followed by the posterior (30%) and central (10%) attachment. 27.5% of the tested menisci were unstable anteriorly and posteriorly. There was no significant difference in the prevalence of rim instability between the type of discoid menisci (complete vs. incomplete), nor was there a significant correlation for age as a risk factor for instability. CONCLUSION: The discoid lateral meniscus has a high prevalence and variable location of peripheral rim instability. Meniscal rim stability must be tested and addressed cautiously in all parts and in all types of discoid lateral menisci during operative treatment.

Patients with discoid menisci have similar clinical outcomes to those without discoid menisci when undergoing surgical intervention: a systematic review.

PURPOSE: To compare post-operative clinical outcomes of discoid meniscus tear procedures such as saucerization with or without repair with those of non-discoid meniscus tears such as meniscectomy or repair in skeletally mature patients with no concomitant injuries. METHODS: Three databases MEDLINE, PubMed and EMBASE were searched from inception to July 3rd, 2022 for literature describing patient-reported outcome measures after meniscus surgery in discoid or non-discoid meniscus tears. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Clinical outcome data on Lysholm, Tegner, International Knee Documentation Committee (IKDC), revision rates, and complications were recorded, with MINORS and Detsky scores used for quality assessment. RESULTS: A total of 38 studies comprising 2213 patients were included with a mean age of 38.6 years (range: 9.0-64.4). The mean follow-up time was 54.1 months (range: 1-234) and the average percentage of female participants was 46.8% (range: 9.5-95.5). The mean change between pre-operative and post-operative Lysholm scores ranged from 21.0-39.0, 7.4-24.1, and 24.2-48.4 in the discoid, non-discoid meniscectomy, and non-discoid repair groups, respectively. The mean change in Tegner scores ranged from 0.0 to 2.3, 1.3, and 0.4-1.3 in the discoid, non-discoid meniscectomy, and non-discoid repair groups, respectively. Pre-operative IKDC scores were not reported, however mean post-operative IKDC scores ranged from 77.4 to 96.0, 46.9 to 85.7, and 63.1 to 94.0 in discoid, non-discoid meniscectomy, and non-discoid repair groups, respectively. Revision rates for discoid procedures, non-discoid meniscectomies, and non-discoid meniscus repairs ranged from 3.2 to 44.0%, 8.3 to 56.0%, and 5.9 to 28.0%, respectively. The most common reasons for revision were acute trauma and persistent pain. CONCLUSION: Discoid saucerization procedures with or without repair leads to similar Lysholm scores as non-discoid repair procedures, and similar IKDC scores and revision rates compared to non-discoid meniscectomy or repair procedures. Patients undergoing discoid procedures appeared to have slightly higher Tegner activity scores compared to patients undergoing non-discoid procedures; however this is to be considered in the context of a younger population of patients undergoing discoid procedures than non-discoid procedures. This information can help guide surgeons in the decision-making process when treating patients with discoid menisci, and should guide further investigations on this topic. LEVEL OF EVIDENCE: IV.

Distal Femoral Focal Deficiency.

Distal femoral focal deficiency is an extremely rare type of congenital femoral deficiency that comprises hypoplasia of the distal femur, with a normally developed hip. We represent a unique case of distal femoral hypoplasia and deficiency of knee extensors, childhood follow-up and final treatment with exarticulation, and a comparison with previous literature.

Preiser's Disease as a Consequence of Scaphoid Hypoplasia After Remote Index Finger Repositioning: A Case Report.

CASE: We present the case of a patient who developed scaphoid avascular necrosis in the setting of scaphoid hypoplasia, 37 years after an index finger repositioning for thumb agenesis, due to Holt-Oram syndrome. CONCLUSION: To the best of our knowledge, this is a unique case of scaphoid avascular necrosis in a patient with Holt-Oram syndrome with scaphoid hypoplasia who underwent index finger repositioning 37 years earlier. Her wrist pain was successfully treated with scaphoid excision and intercarpal fusion.

Novel de novo missense mutation in the interferon regulatory factor 6 gene in an Italian infant with IRF6-related disorder.

BACKGROUND: Congenital maxillomandibular syngnathia is a rare craniofacial anomaly leading to difficulties in feeding, breathing and ability to thrive. The fusion may consist of soft tissue union (synechiae) to hard tissue union. Isolated cases of maxillomandibular fusion are extremely rare, it is most often syndromic in etiology. CASE PRESENTATION: Clinical management of a female newborn with oromaxillofacial abnormities (synechiae, cleft palate, craniofacial dysmorphisms, dental anomaly) and extraoral malformations (skinfold overlying the nails of both halluces, syndactyly, abnormal external genitalia) is presented. The associated malformations addressed to molecular genetic investigations revealing an interferon regulatory factor 6 (IRF6)-related disorder (van der Woude syndrome/popliteal pterygium syndrome). A novel de novo heterozygous mutation in exon 4 of IRF6 gene on chromosome 1q32.2, precisely c.262A > G (p.Asn88Asp), was found. Similarities are discussed with known asparagine missense mutations in the same codon, which may alter IRF6 gene function by reduced DNA-binding ability. A concomitant maternal Xp11.22 duplication involving two microRNA genes could contribute to possible epigenetic effects. CONCLUSIONS: Our reported case carrying a novel mutation can contribute to expand understandings of molecular mechanisms underlying synechiae and orofacial clefting and to correct diagnosing of incomplete or overlapping features in IRF6-related disorders. Additional multidisciplinary evaluations to establish the phenotypical extent of the IRF6-related disorder and to address family counseling should not only be focused on the surgical corrections of syngnathia and cleft palate, but also involve comprehensive otolaryngologic, audiologic, logopedic, dental, orthopedic, urological and psychological evaluations.

A new surgical approach to treatment of bilateral syngnathia in a patient with popliteal pterygium-syndrome.

This case describes the treatment of syngnathia with a popliteal-pterygium syndrome. Although short-term successful surgical treatment has been described in literature, long-term follow up is essential, as the mouth opening limitations can be repetitively reoccurring. This requires new, individual treatment strategies as demonstrated in this case. A young patient is shown, who is successfully undergoing an alloplastic temporomandibular joint replacement to improve mouth opening, increasing the posterior airway space and facilitating the food intake.

Research Note: Comparing methods to assess Valgus-Varus deformity in broiler chickens.

Valgus-varus deformity (VVD) is one of the leg disorders affecting health and welfare of broiler chickens. In research, several protocols are used to determine the prevalence and/or severity of VVD. This study aimed to investigate effects of five different protocols on the angulation of the tibiotarsal-tarsometatarsal joint. Angulation was determined (1) in living chickens with fixation at the femorotibiotarsal joint; (2) in dead chickens without fixation; (3) in dead chickens with fixation; (4) in dissected legs, including muscles, but without skin; (5) in dissected legs, without muscles, but with intact joints. Fixation of the leg at the femorotibiotarsal joint largely reduced the angulation of the tibiotarsal-tarsometatarsal joint. When fixation was used, no differences in angulation were found when broilers were live, dead or legs were dissected, but when no fixation was used, angulation was considerably higher, due to a large lateral deviation of the leg. It can be concluded that in intact chickens, fixation of the femorotibiotarsal joint is essential to determine VVD angulation in an appropriate way.

Diagnostic distribution and postnatal evaluation of prenatally detected short femur: A single center experience.

Genetic skeletal disorders (GSDs) are clinically and etiologically heterogeneous group of disorders caused by abnormal growth and development of bone and/or cartilaginous tissues. Timely and accurate diagnosis is essential for prevention of significant comorbidities. In this study demographic, parental, prenatal and natal characteristics, and postnatal diagnostic distribution along with follow-up processes of 104 individuals with the finding of "short femur" detected in routine prenatal ultrasonography were evaluated. Of 104 patients, 19 (18.2%) were medically terminated, 12 (11.6%) were deceased during follow-up and 73 (70.2%) were still under follow-up. Diagnostic distribution of 104 patients was as follows: 77 (74%) had GSD, eight (7.7%) had chromosomal disorder, seven (6.7%) were completely normal, and 12 (11.5%) had no definite diagnosis. Long-term follow up evaluation contributed to clinical diagnosis in four patients. When grouped according to Nosology and Classification of GSDs: 2019 revision, the most frequent (n = 30, 38.5%) group was "FGFR3 chondrodysplasia group", followed by "Type 2 collagen group" (n = 7, 9%), and "Osteogenesis imperfecta and decreased bone density group" (n = 5, 6.4%). The finding of prenatally detected "short femur" represents a group of diverse diagnosis with heterogeneous etiology. GSDs are the most common etiology among fetuses with short extremity.

TBX5 variant with the novel phenotype of mixed­type total anomalous pulmonary venous return in Holt­Oram Syndrome and variable intrafamilial heart defects.

Variants in T­box transcription factor 5 (TBX5) can result in a wide phenotypic spectrum, specifically in the heart and the limbs. TBX5 has been implicated in causing non­syndromic cardiac defects and Holt­Oram syndrome (HOS). The present study investigated the underlying molecular etiology of a family with heterogeneous heart defects. The proband had mixed­type total anomalous pulmonary venous return (mixed­type TAPVR), whereas her mother had an atrial septal defect. Genetic testing through trio­based whole­exome sequencing was used to reveal the molecular etiology. A nonsense variant was identified in TBX5 (c.577G>T; p.Gly193*) initially showing co­segregation with a presumably non­syndromic presentation of congenital heart disease. Subsequent genetic investigations and more complete phenotyping led to the correct diagnosis of HOS, documenting the novel association of mixed­type TAPVR with HOS. Finally, protein modeling of the mutant TBX5 protein that harbored this pathogenic nonsense variant (p.Gly193*) revealed a substantial drop in the quantity of non­covalent bonds. The decrease in the number of non­covalent bonds suggested that the resultant mutant dimer was less stable compared with the wild­type protein, consequently affecting the protein's ability to bind DNA. The present findings extended the phenotypic cardiac defects associated with HOS; to the best of our knowledge, this is the first association of mixed­type TAPVR with TBX5. Prior to the current analysis, the molecular association of TAPVR with HOS had never been documented; hence, this is the first genetic investigation to report the association between TAPVR and HOS. Furthermore, it was demonstrated that the null­variants reported in the T­box domain of TBX5 were associated with a wide range of cardiac and/or skeletal anomalies on both the inter­and intrafamilial levels. In conclusion, genetic testing was highlighted as a potentially powerful approach in the prognostication of the proper diagnosis.