TRAPPC11-CDG muscular dystrophy: Review of 54 cases including a novel patient.

The trafficking protein particle (TRAPP) complex is a multisubunit protein complex that functions as a tethering factor involved in intracellular trafficking. TRAPPC11, a crucial subunit of this complex, is associated with pathogenic variants that cause a spectrum of disease, which can range from a limb girdle muscular dystrophy (LGMD) to developmental disability with muscle disease, movement disorder and global developmental delay (GDD)/intellectual disability (ID), or even a congenital muscular dystrophy (CMD). We reviewed the phenotype of all reported individuals with TRAPPC11-opathies, including an additional Mexican patient with novel compound heterozygous missense variants in TRAPPC11 (c.751 T > C and c.1058C > G), restricted to the Latino population. In these 54 patients muscular dystrophy signs are common (early onset muscle weakness, increased serum creatine kinase levels, and dystrophic changes in muscle biopsy). They present two main phenotypes, one with a slowly progressive LGMD with or without GDD/ID (n = 12), and another with systemic involvement characterized by short stature, GDD/ID, microcephaly, hypotonia, poor speech, seizures, cerebral atrophy, cerebellar abnormalities, movement disorder, scoliosis, liver disease, and cataracts (n = 42). In 6 of them CMD was identified. Obstructive hydrocephaly, retrocerebellar cyst, and talipes equinovarus found in the individual reported here has not been described in TRAPPC11 deficiency. As in previous patients, membrane trafficking assays in our patient showed defective abnormal endoplasmic reticulum-Golgi transport as well as decreased expression of LAMP2, and ICAM-1 glycoproteins. This supports previous statements that TRAPPC11-opathies are in fact a congenital disorder of glycosylation (CDG) with muscular dystrophy.

Prenatal diagnosis of isolated bilateral clubfoot: Is amniocentesis indicated?

INTRODUCTION: The aim of this study is to evaluate the benefit of cytogenetic testing by amniocentesis after an ultrasound diagnosis of isolated bilateral talipes equinovarus. MATERIAL AND METHODS: This multicenter observational retrospective study includes all prenatally diagnosed cases of isolated bilateral talipes equinovarus in five fetal medicine centers from 2012 through 2021. Ultrasound data, amniocentesis results, biochemical analyses of amniotic fluid and parental blood samples to test neuromuscular diseases, pregnancy outcomes, and postnatal outcomes were collected for each patient. RESULTS: In all, 214 fetuses with isolated bilateral talipes equinovarus were analyzed. A first-degree family history of talipes equinovarus existed in 9.8% (21/214) of our cohort. Amniocentesis was proposed to 86.0% (184/214) and performed in 70.1% (129/184) of cases. Of the 184 karyotypes performed, two (1.6%) were abnormal (one trisomy 21 and one triple X syndrome). Of the 103 microarrays performed, two (1.9%) revealed a pathogenic copy number variation (one with a de novo 18p deletion and one with a de novo 22q11.2 deletion) (DiGeorge syndrome). Neuromuscular diseases (spinal muscular amyotrophy, myasthenia gravis, and Steinert disease) were tested for in 56 fetuses (27.6%); all were negative. Overall, 97.6% (165/169) of fetuses were live-born, and the diagnosis of isolated bilateral talipes equinovarus was confirmed for 98.6% (139/141). Three medical terminations of pregnancy were performed (for the fetuses diagnosed with Down syndrome, DiGeorge syndrome, and the 18p deletion). Telephone calls (at a mean follow-up age of 4.5 years) were made to all parents to collect medium-term and long-term follow-up information, and 70 (33.0%) families were successfully contacted. Two reported a rare genetic disease diagnosed postnatally (one primary microcephaly and one infantile glycine encephalopathy). Parents did not report any noticeably abnormal psychomotor development among the other children during this data collection. CONCLUSIONS: Despite the low rate of pathogenic chromosomal abnormalities diagnosed prenatally after this ultrasound diagnosis, the risk of chromosomal aberration exceeds the risks of amniocentesis. These data may be helpful in prenatal counseling situations.

Duration and outcome of orthotic treatment in children with clubfoot - a four-year follow-up national register study of Swedish children born between 2015 and 2017.

BACKGROUND: The Ponseti method for treating clubfoot consists of initial treatment with serial casting accompanied by achillotenotomy if needed, followed by the maintenance phase including treatment with a foot abduction orthosis (FAO) for at least four years. This study aimed to examine the duration, course, and outcome of orthotic treatment in children with clubfoot. METHODS: 321 children with clubfoot, born between 2015 and 2017, registered in the Swedish Pediatric Orthopedic Quality Register (SPOQ), were included in this prospective cohort study. Data on deformity characteristics and orthotic treatment were extracted. For children with bilateral clubfoot, one foot was included in the analysis. RESULTS: Of the 288 children with isolated clubfoot, 274 children (95.5%) were prescribed an FAO, and 100 children (35%) changed orthosis type before 4 years of age. Of the 33 children with non-isolated clubfoot, 25 children (76%) were prescribed an FAO, and 21 children (64%) changed orthosis type before 4 years of age. 220 children with isolated clubfoot (76%), and 28 children with non-isolated clubfoot (84%) continued orthotic treatment until 4 years of age or longer. Among children with isolated clubfoot, children ending orthotic treatment before 4 years of age (n = 63) had lower Pirani scores at birth compared to children ending orthotic treatment at/after 4 years of age (n = 219) (p = 0.01). It was more common to change orthosis type among children ending orthotic treatment before 4 years of age (p = 0.031). CONCLUSIONS: The majority of children with clubfoot in Sweden are treated with an FAO during the maintenance phase. The proportion of children changing orthosis type was significantly greater and the Pirani score at diagnosis was lower significantly among children ending orthotic treatment before 4 years of age. Long-term follow-up studies are warranted to fully understand how to optimize, and individualize, orthotic treatment with respect to foot involvement and severity of deformity. LEVEL OF EVIDENCE: II.

Prevalence and pattern of congenital clubfoot among less than 5-year-old children in Ethiopia; cross-sectional based study.

BACKGROUND: Clubfoot is one of the most common congenital malformations, but it is also one of the most neglected public health problems among less than five-year-old children, mainly in middle- and low-income countries. Approximately 80% of clubfoot cases are found in low- and middle-income countries. In this study setting, no epidemiological studies have been conducted to assess clubfoot deformity. Due to this gap, the study aimed to assess prevalence, and pattern of congenital club foot among less than 5-year-old children. MATERIALS AND METHODS: An institutional-based cross-sectional study was carried out at Black Lion Specialized Hospital at the pediatric orthopedic clinic. The sample size was 261 to determine the prevalence and pattern of congenital clubfoot. Terms like frequency, percentage, and mean were used for data presentation. RESULT: A total of 36,303 pediatric patients visited Black Lion Specialized Hospital during the study period, and clubfoot prevalence was 7.2 per 1000. The largest subclassification of congenital clubfoot was idiopathic clubfoot, which accounted for 6.2 per 1000, whereas syndromic clubfoot was 0.3 per 1000, and neuropathic clubfoot was shared at 0.36 per 1000. Most of the cases in this study were bilateral clubfoot, with males having more dominance. CONCLUSION: In the area under investigation, a significant prevalence of congenital clubfoot was observed, especially among male children. The majority of cases were bilateral, with idiopathic clubfoot being the dominant form.

Anatomical study of the motor branches of the tibial nerve and incision design for hyperselective neurectomy.

PURPOSE: Selective tibial neurotomy (STN) is a surgical procedure for treating spastic equinovarus foot. Hyperselective neurectomy (HSN) of tibial nerve is a modified STN procedure, which was rarely discussed. This study aimed to describe the branching patterns of the tibial nerve and propose an optimal surgical incision of HSN for treatment of spastic equinovarus foot. METHODS: Sixteen lower limbs were dissected to determine the various branching patterns of the tibial nerve and categorized according to these branching patterns. The mean distances from the nerve entry points to the tip of femur's medial epicondyle were measured, as well as their percentage to the overall length of the leg. The surgical incision was designed according to the range of these nerve entry points. RESULTS: The tibial nerve sent out proximal and distal motor branches based on their position relative to the soleus muscle's tendinous arch. For proximal motor branches, the branches innervating the medial gastrocnemius, lateral gastrocnemius and proximal soleus were categorized into types I (9/16), II (5/16) and III (2/16). Measurements from the medial epicondyle to the nerve entry points into the medial gastrocnemius, lateral gastrocnemius and proximal soleus ranged from 14 to 33 mm (4-9% of leg length), 22-45 mm (6-12%) and 35-81 mm (10-22%), respectively. Distal motor branches including the distal soleus, posterior tibialis, flexor digitorum longus and flexor hallucis longus, were classified as types A (8/14), B (4/14) and C (2/14), with the distances from their respective terminal points to the medial epicondyle were 67-137 mm (19-39%), 74-125 mm (20-35%), 116-243 mm (33-69%) and 125-272 mm (35-77%). CONCLUSIONS: The motor branches of tibial nerve were classified into two groups and each subdivided into three types. Detailed location parameters may serve as an anatomical basis for designing incision of HSN.

Talar neck rotation angle in adults with clubfoot deformity: Observed values and intra- and inter-observer reliability using weightbearing CT.

INTRODUCTION: Adults presenting with symptomatic clubfoot represent a challenging cohort of patients. An appreciation of the location and degree of deformities is essential for management. Talar anatomy is often abnormal with varus within the talar neck, however, there are few reproducible methods which quantify talar neck deformity in adults. We describe a technique of assessing talar neck deformity, and report on observed values and intra- / inter-observer reliability. METHODS: This was a single-centre, retrospective study including 96 feet from 56 adult patients with clubfeet (82 feet had clubfoot deformity, 14 were normal). Mean age was 34.3 ± 16.9 years and 31 (55.3%) were male. Weight-bearing CT scans captured as part of routine clinical care were analysed. Image reformats were oriented parallel to the long axis of the talus in the sagittal plane. In the corresponding axial plane two lines were drawn (on separate slices): 1) a line perpendicular to the intermalleolar axis, 2) a line connecting the midpoints of the talar head and narrowest part of the talar neck. The talar neck rotation angle (TNR angle) was the angle formed between these lines. Intraclass correlation coefficients (ICC) were performed for intra- and inter-observer reliability. RESULTS: Mean TNR angle in clubfeet was 27.6 ± 12.2 degrees (95%CI = 25.0 to 30.2 degrees). Mean TNR angle in normal feet was 18.7 ± 5.1 degrees (95%CI = 16.0 to 21.4 degrees) (p < 0.001). The ICC for clubfeet was 0.944 (95%CI = 0.913 to 0.964) for intra-observer agreement, and 0.896 (95%CI = 0.837 to 0.932) for inter-observer agreement. CONCLUSION: This measurement technique demonstrated excellent intra- and inter-observer agreement. It also demonstrated that compared to normal feet, clubfeet had about 9 degrees of increased varus angulation of the talar neck. This technique and data may be used for future research into clubfoot deformity and in planning treatment. LEVEL OF CLINICAL EVIDENCE: 3.

Calcaneocuboid capsuloligamentous soft-tissue entrapment: a rare cause of acquired equinovarus deformity.

Acquired equinovarus deformity is rare, with most cases related to congenital disorders such as clubfoot. We describe a unique case of traumatic capsuloligamentous soft-tissue entrapment within the calcaneocuboid joint in a 13-year-old girl, causing an acquired equinovarus deformity. This required surgical exploration and joint fixation. Assessing soft-tissue entrapment on magnetic resonance imaging can be beneficial as a potential cause of an acquired post-traumatic non-reducible foot deformity in children. We discuss the intricate capsuloligamentous structures that reinforce the calcaneocuboid joint and highlight the importance of interrogating such structures in the context of inversion injuries to the ankle.

Trends in congenital clubfoot prevalence and co-occurring anomalies during 1994-2021 in Denmark: a nationwide register-based study.

BACKGROUND: Congenital talipes equinovarus (clubfoot) is a common musculoskeletal anomaly, with a suspected multifactorial etiopathogenesis. Herein, we used publicly available data to ascertain liveborn infants with clubfoot delivered in Denmark during 1994-2021, and to classify co-occurring congenital anomalies, estimate annual prevalence, and compare clubfoot occurrence with maternal smoking rates, a commonly reported risk factor. Characterizing this nationwide, liveborn cohort provides a population-based resource for etiopathogenic investigations and life course surveillance. METHODS: This case-cohort study used data from the Danish National Patient Register and Danish Civil Registration System, accessed through the publicly available Danish Biobank Register, to identify 1,315,282 liveborn infants delivered during 1994-2021 in Denmark to Danish parents. Among these, 2,358 infants (65.1% male) were ascertained with clubfoot and classified as syndromic (co-occurring chromosomal, genetic, or teratogenic syndromes) and nonsyndromic (isolated or co-occurring multiple congenital anomalies [MCA]). Annual prevalence estimates and corresponding 95% confidence intervals (CIs) for children with nonsyndromic clubfoot were estimated using Poisson regression and compared with population-based, maternal annual smoking rates obtained from publicly available resources. RESULTS: Infants most often presented with nonsyndromic clubfoot (isolated = 88.6%; MCA = 11.4%); limb and heart anomalies were the most frequently identified MCAs. Prevalence (per 1,000 liveborn infants) was 1.52 (CI 1.45-1.58) for isolated and 0.19 (CI 0.17-0.22) for MCA clubfoot. Prevalence estimates for both isolated and MCA clubfoot remained relatively stable during the study period, despite marked decreases in population-based maternal smoking rates. CONCLUSIONS: From 1994 to 2021, prevalence of nonsyndromic clubfoot in Denmark was relatively stable. Reduction in population-level maternal smoking rates did not seem to impact prevalence estimates, providing some support for the suspected multifactorial etiopathogenesis of this anomaly. This nationwide, liveborn cohort, ascertained and clinically characterized using publicly available data from the Danish Biobank Register, provides a population-based clinical and biological resource for future etiopathogenic investigations and life course surveillance.

What exactly is "foot abduction" during management of idiopathic clubfoot in clinical practice?

PURPOSE: There is however gross ambiguity regarding the use of term "foot abduction" in clubfoot treatment. We measured below defined angles at different stages of clubfoot treatment to decipher their precise interpretation. METHODS: In a prospective evaluation of 25 unilateral clubfeet in infants' age less than six months treated with Ponseti technique, clinical leg foot and thigh foot angle were measured at talar head reduction (LHT0), pre-tenotomy, and post-tenotomy stage. A "normal" reference was available in the form of measurements of contralateral limb. RESULTS: Talar head (LHT0) was reduced at mean leg foot angle of 26 degrees. The corresponding pre- and post-tenotomy angles were 42.6 and 50.0 degrees, respectively. The reference leg foot angles for contralateral limb were 49.8 degrees. The thigh foot angle for LHT0, pre-tenotomy, post-tenotomy, and contralateral side were, respectively, 39.2, 56, 68, and 65.6 degrees. There was an additional tibial external rotation component of mean 13.4 degrees (SD 4.5) in the thigh foot angle when compared to the leg foot angle at tenotomy. This increased to 18 degrees (SD 3.4) post-tenotomy. CONCLUSIONS: The study suggested that the foot abduction described in the "Ponseti Manual" probably intends thigh foot rather than leg foot angles. There was a significant difference in the angles when talar head reduced and tenotomy was decided. The foot abduction is an ambiguous term which should be replaced by the more specific leg or thigh foot abduction angle.

Use of Ankle Dorsiflexion and the Dimeglio and Pirani Scores in Predicting Relapse of Clubfoot Treated With the Ponseti Method.

Although Dimeglio and Pirani scores are frequently employed to rate the severities of clubfoot and to evaluate treatment outcomes, it is unclear if these scores predict relapse after treatment. Ankle dorsiflexion has been suggested in recent years to be a promising predictor of relapse. The aim of this study was to investigate ankle dorsiflexion and Dimeglio and Pirani scores in predicting the relapse of clubfoot after treatment with the Ponseti method. We included patients with clubfoot previously treated by the Ponseti method, and retrospectively analyzed their initial ankle dorsiflexion, Pirani and Dimeglio scores, number of castings, and the occurrence of relapse. We analyzed 218 feet of 176 infants with clubfoot who showed an incidence of relapse of 17.0% (30/176). The mean initial Pirani and Dimeglio scores of the feet showing recurrence were significantly higher than individuals with non-recurrence (p < .001 each). We observed a robust association between Pirani and Dimeglio scores and the recurrence of clubfoot at the last follow-up (γ = 0.53, p = .001). In contrast, ankle dorsiflexion was negatively correlated with recurrence of clubfoot (γ = -0.21, p = .001). Dimeglio scores significantly predicted the recurrence of clubfoot (p = .014). Receiver operating characteristic curve analysis exhibited slightly better performance regarding the Dimeglio score relative to the Pirani score and ankle dorsiflexion in predicting recurrence. Ankle dorsiflexion and Pirani and Dimeglio scores were related to recurrence in patients with clubfoot. However, the Dimeglio score reflected superior accuracy in predicting the prognosis of clubfoot treated with the Ponseti method.

Anterior Distal Tibial Guided Growth for recurrent equinus deformity in idiopathic Congenital Talipes Equinovarus treated with the Ponseti method.

INTRODUCTION: Distal Anterior Tibial Guided Growth has been shown to be useful to correct recurrent equinus deformity after open surgical release for Congenital Talipes Equinovarus. This has not been evaluated in a recurrence after use of the Ponseti method, where soft tissue releases are currently understood as the mainstay of treatment. METHODS: Patients with recurrence of equinus component of CTEV, who underwent DATGG with at least 6-month follow-up were identified retrospectively. The criteria for performing this procedure were (1) equinus not correctable to neutral passively (2) the feeling of a bony block to dorsiflexion clinically as evidenced by a supple Achilles' tendon at maximum dorsiflexion and (3)a finding of a flat-top talus radiologically. Successful treatment was defined by the achievement of heel strike on observation of gait. Details of the index procedure including concurrent procedures, any complications and their treatment, past and subsequent treatment episodes were retrieved from electronic patient records. Pre-op and last available post-op X-rays were evaluated for change in the anterior distal tibial angle and for flat-top talus deformity. RESULTS: We identified 22 feet in 16 patients, with an average follow-up was 25 (8.8-47.3) months. The mean aDTA changed from 88.9 (82.3-94.5) to 77.0 (65.0-83.9) degrees, which was statistically significant (p < 0.0001) using the Paired t-test. Clinically, 17 feet (77 %) obtained a plantigrade foot with a normal heel strike. Complications were identified in 5 feet and include staple migration, oversized staple, superficial infection, iatrogenic varus deformity. Recurrence after completed treatment was noted in one foot. CONCLUSION: This procedure should form a part of the armamentarium of procedures for treating equinus component of CTEV recurrences even in feet not treated previously by open procedures. When used in patients without significant surgical scarring it helps to address bony and soft-tissue factors, leading to effective treatment. LEVEL OF EVIDENCE: Therapeutic Level IV.

Nerve transfer in the spastic equino varus foot: Anatomical feasibility study.

PURPOSE: We want to evaluate the feasibility of transferring a motor branch of the anterior tibial muscle (ATM) to the extensor digitorum longus (EDL) to evaluate this procedure in patients with spastic equinovarus foot (EVF) following post-stroke hemiplegia. METHODS: Ten cadaveric dissections from five fresh frozen human cadavers were performed to establish the anatomic feasibility of transferring a motor branch of the deep peroneal nerve, usually destinated to the ATM, to the branch of the EDL to manage spastic EVF. RESULTS: Six cases (60%) presented three branches destinated to the ATM, one case (10%) presented give branches, and three cases (30%) had four branches. In all specimens, the coaptation between the motor branch to the ATM, referred as the "effector" branch, and the branch of the EDL "receiver" branch was feasible without tension and did not require any intraneural dissection. CONCLUSION: This anatomical study confirms the feasibility of transferring a motor branch from the ATM to the EDL to correct a spastic EVF.

Management of neglected clubfoot in children using Ilizarov external fixator and minimal invasive surgery, Sub-Saharan Africa experience.

PURPOSE: To evaluate the outcomes of Ilizarov external fixator (IEF) and minimal invasive surgery (MIS) in correction of neglected club foot (NCF). METHODS: Thirty-seven feet in 24 child, between five and 15 years old were diagnosed as NCF. All were treated with Achilles tendon lengthening (ATL) and IEF for gradual correction. After IEF removal, cast was applied for six weeks to maintain correction of the deformity. RESULTS: There were 20 boys and four girls. Seven children had left (Lt), four children had right (Rt) while 13 children had bilateral foot deformity. The mean age at surgery was 10.3 (range 5-15) years with an average follow-up of 32.5 (range 24-96) months. All feet were graded as severe according to Pirani score. All feet were corrected after an average six weeks in IEF. After two years follow-up, 23 feet (16 patients) showed good results, five feet (3 patients) showed fair results and four feet (2 patients) had Rt side foot fair result while the Lt foot had good result in both patients. Five feet (3 patients) showed poor results. Eight patients had pin site infection. One case had infected skin and subcutaneous tissue and needed debridement. Two cases developed skin sloughing, changes in color and needed close follow-up. CONCLUSION: We recommend combined IEF and MIS as a suitable, efficient and successful salvage procedure in the management of severe idiopathic NCF in children especially in developing countries.

Neuro-Orthopedic Surgery for Equinovarus Foot Deformity in Adults: A Narrative Review.

Neuro-orthopedic surgery is an alternative to the conservative treatment of spastic equinovarus foot (SEF) in adults. The objective of the present narrative review was to summarize current practice with regard to patient assessment, the choice of treatment, the various neuro-orthopedic procedures, and the latter's outcomes. We searched literature databases (MEDLINE, EMBASE, Cochrane) for original articles or opinion papers on surgical treatment of spastic equinovarus foot in adults. Neuro-orthopedic approaches require a careful analysis of the patient's and/or his/her caregiver needs and thus relevant treatment goals. Surgical planning requires detailed knowledge of impairments involved in the spastic equinovarus foot deformity based on a careful clinical examination and additional information from diagnostic nerve blocks and/or a quantitative gait analysis. Procedures mainly target nerves (neurotomy) and tendons (lengthening, transfer, tenotomy). These procedures reduce impairments (spasticity, range of motion, and foot position), improve gait and walking function, but their impact on participation and personalized treatment goals remains to be demonstrated. Neuro-orthopedic surgery is an effective treatment option for spastic equinovarus foot in adults. However, practice is still very heterogeneous and there is no consensus on the medical strategies to be applied before, during and after surgery (particularly the type of anesthesia, the need for immobilization, rehabilitation procedures).

Factors Causing Dropout From Treatment During the Ponseti Method of Clubfoot Management: The Caregivers' Perspective.

A retrospective comparative study was conducted, aiming to identify factors associated with dropout from clubfoot treatment by Ponseti method in low- and middle-income countries. A prospectively gathered database of patients who received treatment at a high-volume urban clubfoot clinic over 6 years was queried for dropouts. A "dropout" was identified as any child that had not had a visit within 3 weeks of casting, 4 weeks of tenotomy or 6 months of brace follow-up. The second part of the study was a telephonic interview with caregivers of the identified dropouts to ascertain their reasons for discontinuing treatment. Of the 965 patients treated during the study period, there were 155 (16.06%) dropouts-137 (88.38%) during bracing phase and 18 (11.62%) during casting phase. Age at presentation was significantly higher among the dropouts as compared to those who did not dropout (median 9.5 and 7 months for casting and bracing dropouts respectively versus 3.5 months for regular follow-ups, p < .001). No significant correlation was found between patient dropout and sex (p = .061), or laterality (p = .071). Thirty-seven caregivers (23.8%) could be contacted telephonically; including 6 casting and 31 bracing dropouts. The most commonly cited reason for dropout from treatment was lack of family support (75.7%), followed by distance to the clinic (59.5%) and unavailability of transport (54.1%). Sixteen caregivers (43.2%) dropped out on account of migration to another town/state. Maintenance of a meticulous registry with regular update of caregivers' contact details, and interventions to mitigate the identified hurdles can help in reducing treatment dropouts.

The effectiveness of three-phase physiotherapy program in children with clubfoot after Ponseti treatment.

BACKGROUNDS: Clubfoot is a foot disorder frequently seen. Although, there are several studies about the efficiency of physiotherapy in the treatment of clubfoot, physiotherapy programs may be more efficient if the treatment apply step by step similar to the logic of the serial casting progression of the involved foot. Therefore, the aim of this study was to determine the effectiveness of three-phase physiotherapy program in children with clubfoot. METHODS: Fifty-seven patients (37 males, 20 females; 7.26 ± 1.27 years) with clubfoot which had Ponseti treatment before were included. The ankle dorsiflexion (DF) and plantar flexion (PF) ranges of motion (ROM), one-leg standing time, sit-to-stand test, The Oxford Ankle Foot Questionnaire (OxAFQ) and treatment satisfaction were evaluated before and after treatment. A three-phase physiotherapy program was applied for 3 months. RESULTS: DF, PF, one-leg standing time, sit-to-stand test, treatment satisfaction and all parameters of OxAFQ except 'Emotional' parameter of OxAFQ-Children significantly improved after treatment (p < 0.05). CONCLUSIONS: The three-phase physiotherapy program increased the ankle range of motion, improved functional status and treatment satisfaction in children with clubfoot. The three-phase physiotherapy might be a reasonable treatment for clubfoot. Although, there is a need for long-term studies to understand its effects on preventing relapse.

Identification of a novel pathogenic variant in CKAP2L and literature review in a child with Filippi syndrome and congenital talipes equinovarus.

Filippi syndrome (MIM #272440), one of the craniodigital syndromes, is a rare genetic entity with autosomal recessive inheritance and characterized by pre- and postnatal growth retardation, microcephaly, distinctive facial appearance, developmental delay/intellectual disability, and variable syndactylies of the fingers and toes. In this report, a further female patient of Filippi syndrome who additionally had a unilateral congenital talipes equinovarus (CTEV), a feature not previously recorded, is described. Genetic testing revealed a novel homozygous frameshift pathogenic variant (c.552_555delCAAA, p.Asn184Lysfs*8) in CKAP2L and thus confirmed the diagnosis of Filippi syndrome. We hope that the newly recognized feature (CTEV) will contribute to expand the clinical spectrum of this extremely rare condition. In view of the paucity of reported cases, the full spectrum of clinical findings of Filippi syndrome necessitates obviously further affected individuals/pedigrees delineation in order to elucidate the etiological and phenotypic aspects of this orphan disease appropriately.

Minoxidil decreases collagen I deposition and tissue-like contraction in clubfoot-derived cells: a way to improve conservative treatment of relapsed clubfoot?

AIM: Clubfoot is a congenital deformity affecting the musculoskeletal system, resulting in contracted and stiff tissue in the medial part of the foot. Minoxidil (MXD) has an inhibitory effect on lysyl hydroxylase, which influences the quality of extracellular matrix crosslinking, and could therefore be used to reduce the stiffness and to improve the flexibility of the tissue. We assessed the in vitro antifibrotic effects of minoxidil on clubfoot-derived cells. METHODS: Cell viability and proliferation were quantified by xCELLigence, MTS, and LIVE/DEAD assays. The amount of collagen I deposited into the extracellular matrix was quantified using immunofluorescence with subsequent image segmentation analysis, hydroxyproline assay, and Second Harmonic Generation imaging. Extracellular matrix contraction was studied in a 3D model of cell-populated collagen gel lattices. RESULTS: MXD concentrations of 0.25, 0.5, and 0.75 mM inhibited the cell proliferation in a concentration-dependent manner without causing a cytotoxic effect. Exposure to ≥0.5 mM MXD resulted in a decrease in collagen type I accumulation after 8 and 21 days in culture. Changes in collagen fiber assembly were observed by immunofluorescence microscopy and nonlinear optical microscopy (second harmonic generation). MXD also inhibited the contraction of cell-populated collagen lattices (0.5 mM by 22%; 0.75 mM by 28%). CONCLUSIONS: Minoxidil exerts an in vitro inhibitory effect on the cell proliferation, collagen accumulation, and extracellular matrix contraction processes that are associated with clubfoot fibrosis. This study provides important preliminary results demonstrating the potential relevance of MXD for adjuvant pharmacological therapy in standard treatment of relapsed clubfoot.

Loeys-Dietz Syndrome.

Loeys-Dietz syndrome is an autosomal dominant aortic aneurysm syndrome characterized by multisystemic involvement. The most typical clinical triad includes hypertelorism, bifid uvula or cleft palate and aortic aneurysm with tortuosity. Natural history is significant for aortic dissection at smaller aortic diameter and arterial aneurysms throughout the arterial tree. The genetic cause is heterogeneous and includes mutations in genes encoding for components of the transforming growth factor beta (TGFß) signalling pathway: TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 and TGFB3. Despite the loss of function nature of these mutations, the patient-derived aortic tissues show evidence of increased (rather than decreased) TGFß signalling. These insights offer new options for therapeutic interventions.

Correlation of radiographic parameters with clinical correction in idiopathic congenital talipes equinovarus undergoing Ponseti treatment.

PURPOSE: Idiopathic congenital talipes equinovarus is the most commonly encountered congenital deformity of the foot. Ponseti technique of manipulation is the treatment of choice. The Pirani classification is a reliable scoring system for clinical evaluation of clubfeet. The role of radiographic parameters in the evaluation and treatment of clubfeet is still controversial. The aim of this study was to evaluate the correlation of radiological parameters with clinical correction in patients with idiopathic clubfeet undergoing correction using Ponseti method. METHODS: Between March 2018 and March 2019, 42 feet in 27 patients with idiopathic clubfeet were treated in our hospital. We used the Pirani scoring system for clinical evaluation. Anteroposterior and lateral views of the feet were taken before and after correction and at the last follow-up. The anteroposterior view was evaluated for the talocalcaneal angle and talo-first metatarsal angle, while the lateral view was only evaluated for the talocalcaneal angle. RESULTS: Twelve were boys (44.4%), and 15 were girls (55.6%). The deformity was bilateral in 15 patients (55.6%) and unilateral in 12 patients (44.4%). The average age was three months. According to the Pirani score, the mean Pirani Total score was 4.4 before correction and reduced to 0.4 after correction. The mean talocalcaneal angle in anteroposterior and lateral views was 15.1° and 7.8° before correction, increased to 32.7° and 31.8° after correction, respectively. The mean talocalcaneal index increased from 23.2 before correction to 64.5 after correction. The mean talo-first metatarsal angle in anteroposterior view improved from 25.7° before correction to - 1.6° after correction. The relation between the differences in Pirani scores before and after correction and the differences in measured radiographic parameters before and after correction revealed a statistically significant correlation. CONCLUSION: Radiographic parameters showed a statistically significant correlation with the clinical outcome. Thus, evaluation of clubfeet correction treated by Ponseti technique can rely mainly on clinical scores with limited utilization of radiological assessment.