＜Editors' Choice＞ The relationship between preoperative foot alignment and postoperative outcomes in patients who underwent initial total knee arthroplasty.

We compared the relationship between foot alignments and quality of life in patients who underwent initial total knee arthroplasty (TKA). Among the patients with knee osteoarthritis (KOA) who underwent TKA from May 2015 to May 2017 at our hospital, we focused on those in whom weight-bearing foot radiographs had been evaluated preoperatively. The hallux valgus angle and Meary angle were measured by preoperative radiography, and those with hallux valgus angles of 20 degrees or more were classified into the hallux valgus (HV) group, and those with Meary angles of 4 degrees or more into the high arch (HA) group. Also knee and ankle range of motion, knee pain Visual Analog Scale, and the 36-item short-form health survey (SF-36) were measured preoperatively and at discharge, and the amount of these changes was compared in the presence/absence of HV and HA. Regarding HV, there were no significant differences in any of these items between the HV and non-HV groups. However, the SF-physical function was significantly lower in the HA group than in the normal group. In addition, ankle dorsiflexion was lower in the HA group than that in the normal group, although this difference was not statistically significant. There was little improvement of the ankle dorsiflexion, and it was associated with deterioration of the physical function items of SF-36. In total knee arthroplasty patients with HA, physical therapy of the ankles and feet, as well as of the knees, was considered to enhance the improvement of physical function.

Preoperative predictive factors affecting return to work in patients with gliomas undergoing awake brain mapping.

PURPOSE: This study aimed to investigate the preoperative predictive factors affecting return to work in patients with gliomas in the left cerebral hemisphere undergoing awake surgery. METHODS: We retrospectively reviewed 50 consecutive glioma patients who underwent awake surgery from January 2012 to July 2017. Adult patients older than 18 years, who reported working prior to surgery, were recruited for this study. RESULTS: Comparing sociodemographic, disease-related and preoperative neurocognitive variables of glioma patients who returned to work and those who did not, binomial logistic regression models for preoperative predictors affecting return to work revealed significant differences in age and sole breadwinner status as sociodemographic variables, tumour volume as a disease-related variable, and Verbal IQ, Performance IQ, general memory, attention/concentration, and working memory as neurocognitive variables. Multivariate logistic regression models demonstrated that the independent factors associated with propriety of returning to work 1 year after surgery was the sociodemographic variable sole breadwinner status (yes vs no; OR = 15.00, 95% CI 2.22-101.35, p = 0.01), the disease-related variable tumour volume (per 1 cm3; OR = 0.98, 95% CI 0.96-0.99, p = 0.04), and the preoperative neurocognitive variable general memory (≥ 100 vs < 100; OR = 21.70, 95% CI 2.60-183.94, p = 0.01). CONCLUSIONS: Our results suggest that three predictive factors including sole breadwinner status, tumour volume and general memory that can be assessed in the preoperative stage substantially contribute to returning to work in patients with gliomas in the left cerebral hemisphere, 1 year after awake surgery.

Cilostazol use is associated with FIM cognitive improvement during convalescent rehabilitation in patients with ischemic stroke: a retrospective study.

Cilostazol is a phosphodiesterase III-inhibiting antiplatelet agent that is often used to prevent stroke and peripheral artery disease, and its administration has shown significant improvements for cognitive impairment. We investigate the potential of cilostazol for reducing or restoring cognitive decline during convalescent rehabilitation in patients with non-cardioembolic ischemic stroke. The study sample included 371 consecutive patients with lacunar (n = 44) and atherothrombosis (n = 327) subtypes of non-cardioembolic ischemic stroke (224 men and 147 women; mean age, 72.9 ± 8.1 years) who were required for inpatient convalescent rehabilitation. Their medical records were retrospectively surveyed to identify those who had received cilostazol (n = 101). Patients were grouped based on cilostazol condition, and Functional Independence Measure (FIM) scores (total and motor or cognitive subtest scores) were assessed both at admission and discharge. The gain and efficiency in FIM cognitive scores from admission to discharge were significantly higher in patients who received cilostazol than those who did not (p = 0.047 and p = 0.035, respectively); we found no significant differences in other clinical factors or scores. Multiple linear regression analysis confirmed that cilostazol was a significant factor in FIM cognitive scores at discharge (ß = 0.041, B = 0.682, p = 0.045); the two tested dosages were not significantly different (100 mg/day, n = 43; 200 mg/day, n = 58). Cilostazol can potentially improve cognitive function during convalescent rehabilitation of patients with non-cardioembolic ischemic stroke, although another research must be needed to confirm this potential.

Clinical Benefit of Preoperative Exercise and Nutritional Therapy for Patients Undergoing Hepato-Pancreato-Biliary Surgeries for Malignancy.

BACKGROUND: The impact of prehabilitation on physical fitness and postoperative course after hepato-pancreato-biliary (HPB) surgeries for malignancy is unknown. The current study aimed to investigate the effect of preoperative exercise and nutritional therapies on nutritional status, physical fitness, and postoperative outcomes of patients undergoing an invasive HPB surgery for malignancy. METHODS: Patients who underwent open abdominal surgeries for HPB malignancies (major hepatectomy, pancreatoduodenectomy, or hepato-pancreatoduodenectomy) between 2016 and 2017 were subjected to prehabilitation. Patients before the introduction of prehabilitation were included as historical control subjects for 1:1 propensity score-matching (no-prehabilitation group). The preoperative nutritional status and postoperative course were compared between the two groups. RESULTS: The prehabilitation group consisted of 76 patients scheduled to undergo HPB surgeries for malignancy. An identical number of patients were selected as the no-prehabilitation group after propensity score-matching. During the waiting period, serum albumin levels were significantly deteriorated in the no-prehabilitation group, whereas this index did not deteriorate or even improved in the prehabilitation group. By performing prehabilitation, a 6-min walk distance and total muscle/fat ratio were significantly increased during the waiting period. Although the overall incidence of postoperative complications did not differ between the two groups, the postoperative hospital stay was shorter in the prehabilitation group than in the no-prehabilitation group (median, 23 vs 30 days; p = 0.045). CONCLUSION: The introduction of prehabilitation prevented nutritional deterioration, improved physical fitness before surgery, and shortened the postoperative hospital stay for the patients undergoing HPB surgeries for malignancy.

Impact of variation in physical activity after total joint replacement.

PURPOSE: Patients who undergo total knee arthroplasty (TKA) or total hip arthroplasty (THA) often develop postoperative pain. Exercise approaches are recommended postoperatively; however, the impact of excessive variation in physical activity is unclear. The purpose of the present preliminary study was to investigate the impact of excessive variation in physical activity using the accelerometer in the early period after TKA or THA. PATIENTS AND METHODS: Seventy-two patients were enrolled in the study. Forty patients underwent initial TKA, and 32 initial THA. Physical activity was measured for 8 days from postoperative day 3 to 10. Patients with substantial correlation between physical activity and postoperative day were classified as the "good-pacing" group. Patients with no correlation between them were classified as the "poor-pacing" group. They were also evaluated using a pain visual analog scale (VAS), pain catastrophizing scale, and hospital anxiety and depression scale. RESULTS: The average age was 68 years, and 59 patients (82%) were women. The average maximum number of steps per day was 2,181. There were 45 patients with good pacing and 27 with poor pacing. The poor-pacing group showed significantly lower maximum number of steps per day, higher postoperative average VAS score, higher postoperative worst VAS score, and longer duration of postoperative hospital stay than the good-pacing group. CONCLUSION: Patients with excessive variation in physical activity showed severe postoperative pain and prolonged postoperative hospital stay. The postoperative variation in physical activity could be an outcome for improvement in patients after lower-limb arthroplasty.

Changes in the range of motion of the lower limb joints during extensive tibial lengthening in achondroplasia.

Increase in the magnitude of lengthening during the limb lengthening procedure involves a high risk of decreased range of motion (ROM) in adjacent joints. Even though patients with achondroplasia can tolerate a relatively larger amount of lengthening owing to its inherent soft-tissue laxity, they often exhibit significant joint contractures during extensive lengthening. In the present study, we evaluated temporal changes in the ROM of the hip, knee, and ankle joints throughout the treatment period in 12 limbs of six patients with achondroplasia who had undergone extensive tibial lengthening. The ROM of hip extension, knee extension, and ankle dorsiflexion were measured before distraction, at every 1-cm length gained during distraction, and at monthly intervals after the termination of distraction until the frame removal. The average amount of lengthening was 9.2±1.2 cm, corresponding to 52.8±6.8% of the original bone length. Equinus deformity of the ankle was observed in the early phase of distraction, whereas flexion contracture of the knee and hip appeared in the middle and the late phase of distraction, respectively. With dedicated physiotherapy and deliberate orthosis wearing, all of the contracture gradually resolved up to the preoperative state after the termination of distraction. This is the first report showing the development of contracture in the hip, a nonadjacent joint for the tibial lengthening.

Chronic lateral epiphyseal separation of the proximal tibia causes late-onset tibia vara.

An adolescent obese boy showed late-onset unilateral tibia vara associated with physeal separation (slipped epiphysis) of the lateral proximal tibia and physeal widening of the lateral distal femur. These affected physes showed normal signal intensities by MRI. He was treated with lateral hemiepiphysiodesis of the left proximal tibia and the distal femur using two parallel eight-Plates, and varus deformity rapidly improved postoperatively without recurrence. This is the first case of late-onset tibia vara caused by lateral physeal separation of the proximal tibia. Normal growth of the medial physes around the knee would contribute toward significant correction after surgery.

Post-operative delayed ambulation after thymectomy is associated withpre-operative six-minute walk distance.

OBJECTIVE: Delayed post-operative ambulation is a risk of post-operative complications and increases overall healthcare costs. We investigated pre-operative and intraoperative variables associated with delayed ambulation in patients who underwent thymectomy. METHODS: A total of 57 consecutive patients undergoing thymectomy were included in this study. Pre-operative functional exercise capacity was evaluated by six-minute walk distance. Ambulation was considered to be delayed if the patient could not walk the ward on post-operative day 1. Binary logistic regression analysis was performed to clarify the factors associated with delayed ambulation. RESULTS: Pre-operative six-minute walk distance was the only significant variable that was associated with delayed ambulation. The area under the receiver operating characteristic curve for predicting delayed ambulation was 0.684 (95% confidential interval: 0.546-0.823, p = 0.017), and the optimal discriminatory pre-operative six-minute walk distance value was 498 m. Post-operative hospital stay was significantly longer in patients with low six-minute walk distance (<498 m) than those with high six-minute walk distance (≥498 m). In contrast, the presence of myasthenia gravis or adjuvant chemoradiotherapy was not associated with delayed ambulation. CONCLUSIONS: Our results suggest that low pre-operative six-minute walk distance is associated with delayed post-operative ambulation and longer post-operative hospital stay in patients who underwent thymectomy. Implications for rehabilitation The predictors for delayed ambulation after thymectomy are not fully investigated. The presence of myasthenia gravis was not associated with delayed ambulation. Low pre-operative six-minute walk distance was associated with delayed ambulation.

Associations among pain catastrophizing, muscle strength, and physical performance after total knee and hip arthroplasty.

AIM: To investigate whether reductions in pain catastrophizing associated with physical performance in the early period after total knee arthroplasty (TKA) or total hip arthroplasty (THA). METHODS: The study group of 46 participants underwent TKA or THA. The participants were evaluated within 7 d before the operation and at 14 d afterwards. Physical performance was measured by the Timed Up and Go (TUG) test, and 10-m gait time was measured at comfortable and maximum speeds. They rated their knee or hip pain using a visual analog scale (VAS) for daily life activities. Psychological characteristics were measured by the Pain Catastrophizing Scale (PCS). Physical characteristics were measured by isometric muscle strength of knee extensors and hip abductors on the operated side. The variables of percent changes between pre- and post-operation were calculated by dividing post-operation score by pre-operation score. RESULTS: Postoperative VAS and PCS were better than preoperative for both TKA and THA. Postoperative physical performance and muscle strength were poorer than preoperative for both TKA and THA. The percent change in physical performance showed no correlation with preoperative variables. In TKA patients, the percent change of PCS showed correlation with percent change of TUG (P = 0.016), 10-m gait time at comfortable speeds (P = 0.003), and 10-m gait time at maximum speeds (P = 0.042). The percent change of muscle strength showed partial correlation with physical performances. The percent change of VAS showed no correlation with physical performances. On the other hand, in THA patients, the percent change of hip abductor strength showed correlation with percent change of TUG (P = 0.047), 10-m gait time at comfortable speeds (P = 0.001), and 10-m gait time at maximum speeds (P = 0.021). The percent change of knee extensor strength showed partial correlation with physical performances. The percent change of VAS and PCS showed no correlation with physical performances. CONCLUSION: Changes in pain catastrophizing significantly associated with changes in physical performance in the early period after TKA. It contributes to future postoperative rehabilitation of arthroplasty.

Combination Treatment of Perioperative Rehabilitation and Psychoeducation Undergoing Thoracic Surgery.

Postoperative pulmonary complications are a risk associated with thoracic surgery. However, there have been few reports on cases at high risk of postoperative complications. Cancer patients often have negative automatic thoughts about illness, and these negative automatic thoughts are associated with reduced health behavior and physical activity. This case series demonstrates the successful combination treatment of perioperative rehabilitation and psychoeducation for negative automatic thoughts in two cancer patients who underwent thoracic surgery. One patient underwent pneumonectomy with laryngeal recurrent nerve paralysis; the other patient, who had a history of recurrent hepatic encephalopathy and dialysis, underwent S6 segmentectomy. Both patients had negative automatic thoughts about cancer-related stress and postoperative pain. The physical therapists conducted a perioperative rehabilitation program in which the patients were educated to replace their maladaptive thoughts with more adaptive thoughts. After rehabilitation, the patients had improved adaptive thoughts, increased physical activity, and favorable recovery without pulmonary complications. This indicates that the combination treatment of perioperative rehabilitation and psychoeducation was useful in two thoracic cancer surgery patients. The psychoeducational approach should be expanded to perioperative rehabilitation of patients with cancer.

Preoperative 6-minute walk distance accurately predicts postoperative complications after operations for hepato-pancreato-biliary cancer.

BACKGROUND: Operation for hepato-pancreato-biliary cancer is among the most invasive open abdominal operations, with a high postoperative morbidity and mortality rate. The purpose of the present study is to investigate whether a preoperative 6-minute walk distance can predict major postoperative complications after operation for hepato-pancreato-biliary diseases. METHODS: A total of 81 participants who underwent pancreaticoduodenectomy, major hepatectomy with extrahepatic bile duct resection, or hepatopancreatoduodenectomy were included. The 6-minute walk distance was performed within 1 week before operation. Patients were categorized into 2 groups based on surgical complications: Clavien-Dindo grade <3 and Clavien-Dindo grade ≥3. Clinical differences between the 2 groups were analyzed. Multivariate logistic regression analysis was performed to identify risk factors for postoperative complications that were categorized as Clavien-Dindo grade ≥3. RESULTS: The multiple logistic regression model revealed a significant correlation between major postoperative complications and preoperative low 6-minute walk distance, low body mass index, and major blood loss. In patients with 6-minute walk distance <400 m (1,312 feet), the Clavien-Dindo grade was considerably greater than patients with ≥400 m. CONCLUSION: The 6-minute walk distance is useful in identifying patients with a greater chance of developing major postoperative complications after surgery for hepato-pancreato-biliary cancer.

Combination of Continuous Epidural Block and Rehabilitation in a Case of Complex Regional Pain Syndrome.

Epidural analgesia is used to promote rehabilitation in patients with refractory complex regional pain syndrome (CRPS) who cannot bear physical programs due to intense pain. However, the actual rehabilitation process has not been focused in previous reports. Here, we outline our experience of treating a young woman with CRPS type 1 who underwent rehabilitation facilitated by a continuous lumbar epidural block. A 15-year-old girl developed throbbing pain from her left toe to her ankle, with no obvious cause. She was admitted to the hospital 2 months after symptom onset for an assessment of pain intensity, range of motion, weight-bearing, neglect-like symptoms, pain catastrophizing, and a CRPS severe score with impaired activities of daily living. The rehabilitation program was initiated under facilitation of continuous epidural block. Her rehabilitation program included physical therapy, motor imagery, mirror therapy, and cognitive behavioral therapy. The intensity of the exercise was gradually increased without exacerbating her symptoms. Ultimately, she recovered completely after a continuous epidural block for 21 days and rehabilitation for 80 days. A combination of continuous epidural block and intensive rehabilitation improved the symptoms of this patient. The treatment course would be helpful for planning rehabilitation programs in other patients with CRPS.

Gait Speeds Associated with Anxiety Responses to Pain in Osteoarthritis Patients.

OBJECTIVE: Patients with lower limbs osteoarthritis (OA) had slower walking speeds than healthy. Gait speed, which is associated with leg muscle strength, is a consistent predictor of health and functional status. The effects of pain and pain-related psychological constructs for gait speeds have been uncertain. Therefore, we investigated whether gait speed in patients with OA of lower limbs is associated with pain-related psychological constructs using a performance-based measure. METHODS: The study group comprised 59 patients with advanced knee or hip OA. Gait speeds were measured at comfortable and maximum levels during 10-m walks. Covariates included 1) pain intensity measured with a visual analogue scale (VAS), 2) psychological constructs measured with a short-version pain anxiety symptoms scale (PASS-20) and the hospital anxiety and depression scale (HADS), and 3) bilateral knee extensor and hip abductor muscle strength. Each variable was subjected to multivariate analysis with gait speed. RESULTS: Single regression analysis showed that gait speeds were significantly correlated with VAS and PASS-20 scores, and muscle strength, not with HADS. Multiple regression analysis showed that PASS-20 score was significant correlating factor for gait speeds. CONCLUSIONS: Anxiety-related responses to pain were significant correlating factor for gait speeds, in patients with OA of lower limbs.

Association of Leukoaraiosis With Convalescent Rehabilitation Outcome in Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: We investigated the factors influencing inpatient convalescent rehabilitation outcomes in patients with ischemic stroke, particularly severity of leukoaraiosis on magnetic resonance imaging. METHODS: Participants included 520 patients with ischemic stroke (317 men and 203 women; mean age, 72.8±8.4 years) who were transferred from acute care hospitals for inpatient convalescent rehabilitation. Ischemic stroke subtypes included lacunar infarction (n=41), atherothrombosis (n=223), artery-to-artery embolism (n=67), cardiogenic embolism (n=97), undetermined embolism (n=76), and uncategorized ischemic stroke (n=16). Leukoaraiosis was graded according to periventricular hyperintensity (PVH) and deep white matter hyperintensity on magnetic resonance imaging. Functional Independence Measure scores were assessed on admission and at discharge. RESULTS: Multiple regression analysis revealed that rehabilitation outcomes, measured as total Functional Independence Measure scores, were significantly associated with leukoaraiosis estimated by PVH grade. This association was observed after adjustment for factors such as severity, age, and poststroke history. In all patients, PVH grades were associated with Functional Independence Measure motor scores (P<0.001), whereas in patients with artery-to-artery embolism or cardiogenic embolism and deep white matter hyperintensity grades were associated with Functional Independence Measure cognitive scores (P<0.05). CONCLUSIONS: Our study revealed that the degree of leukoaraiosis was associated with inpatient convalescent rehabilitation outcome in patients with ischemic stroke. Furthermore, the PVH grade was associated with motor function outcome, whereas the deep white matter hyperintensity grade correlated with cognitive function outcome, likely because the progression patterns and anatomic backgrounds of PVH and deep white matter hyperintensity differ according to ischemic stroke subtype.

Low bone mineral density in achondroplasia and hypochondroplasia.

BACKGROUND: Achondroplasia (ACH) and hypochondroplasia (HCH) are the most common form of short-limb skeletal dysplasias caused by activated fibroblast growth factor receptor 3 (FGFR3) signaling. Although decreased bone mass was reported in gain-of-function mutation in Fgfr3 mice, both disorders have never been described as osteoporotic. In the present study, we evaluated bone mineral density (BMD) in ACH and HCH patients. METHODS: We measured spinal BMD (L1-L4) in 18 ACH and four HCH patients with an average age of 19.8 ± 7.5 years (range, 10-33 years). BMD Z-score in each individual was calculated for normalizing age and gender. Correlation between body mass index (BMI) and BMD was analyzed. Moreover, BMD and Z-score were compared between ACH patients and HCH patients. RESULTS: The average BMD of ACH/HCH patients was 0.805 ± 0.141 g/cm(2) (range, 0.554-1.056 g/cm(2) ), resulting in an average Z-score of -1.1 ± 0.8 (range, -2.4 to 0.6) of the standard value. A slightly positive correlation was observed between BMI and BMD (r = 0.45; P = 0.13). There was no significant difference in BMD and Z-score between ACH and HCH patients. CONCLUSION: Spinal BMD was reduced in ACH/HCH patients, and was mildly correlated with individual BMI. We should carefully monitor BMD and examine osteoporosis-related symptoms in adolescent and adult ACH/HCH patients. © 2016 Japan Pediatric Society.

Prediction of Clinically Significant Leg-Length Discrepancy in Congenital Disorders.

Leg-length discrepancy greater than 2 to 2.5 cm can potentially have an adverse effect on our walking and standing mechanisms and requires proper correction involving surgical treatment. However, for minor leg-length discrepancy in childhood, decision making for the indications for and timing of epiphysiodesis is difficult because of unpredictable final discrepancy. The purpose of this study was to analyze longitudinal changes of minor leg-length discrepancy in congenital disorders and to determine earlier predictive values for the clinically significant discrepancy. Twenty-one patients with congenital disorders who had minor leg-length discrepancy less than 2 cm at the first presentation were retrospectively evaluated. The patients were divided into 2 groups according to leg-length discrepancy at latest follow-up: the significant group (n=11) had 25 mm or more of leg-length discrepancy and the minor group (n=10) had less than 25 mm of leg-length discrepancy. The authors evaluated longitudinal changes of leg-length discrepancy within the first 10 years by mixed-effects regression model. All patients showed monotonically increasing leg-length discrepancy with age, except for 2 (neurofibromatosis type 1 and macrodactyly of the foot) who demonstrated fluctuating leg-length discrepancy. Mean annual rate of leg-length discrepancy change in the significant group was 2.1 mm across the first decade of life and was significantly larger than that in the minor group (difference in slope, 1.3 mm; P<.0001). In minor leg-length discrepancy associated with congenital disorders, the incidence of clinically significant leg-length discrepancy can be predictable by the annual rate of leg-length discrepancy change in the first decade of life.

Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial.

BACKGROUND: Currently, there are no effective medical treatment options to prevent the formation of heterotopic bones in fibrodysplasia ossificans progressiva (FOP). By the drug repositioning strategy, we confirmed that perhexiline maleate (Pex) potentially ameliorates heterotopic ossification in model cells and mice. Here, we conducted a prospective study to assess the efficacy and safety of Pex in the treatment of FOP patients. METHODS: FOP patients in this open-label single-center study were treated with Pex for a total of 12 months, and followed up for 12 consecutive months after medication discontinuation. The safety of the treatment was assessed regularly by physical and blood examinations. The efficacy of Pex for preventing heterotopic ossifications was evaluated by the presence of flare-ups, measurements of serum bone markers, and changes in the total bone volume calculated by the three-dimensional computed tomography (3D-CT) images. RESULTS: Five patients with an average age of 23.4 years were enrolled. Within safe doses of Pex administration in each individual, there were no drug-induced adverse effects during the medication phase. Three patients showed no intense inflammatory reactions during the study period, while two patients had acute flare-ups around the hip joint without evidence of trauma during the medication phase. In addition, one of them became progressively incapable of opening her mouth over the discontinuation phase. Serum levels of alkaline phosphatase (ALP) and bone specific ALP (BAP) were significantly and synchronously increased with the occurrence of flare-ups. Volumetric 3D-CT analysis demonstrated a significant increase in the total bone volume of Case 2 (378 cm(3)) and Case 3 (833 cm(3)) during the two-year study period. CONCLUSIONS: We could not prove the efficacy of oral Pex administration in the prevention of heterotopic ossifications in FOP. Serum levels of ALP and BAP appear to be promising biomarkers for monitoring the development of ectopic ossifications and efficacy of the therapy. Quantification of change in the total bone volume by whole body CT scanning could be a reliable evaluation tool for disease progression in forthcoming clinical trials of FOP.

A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small patella syndrome.

The phenotypic similarities have been demonstrated between non-lethal campomelic dysplasia (CD) and small patella syndrome (SPS), in which different genetic defects have been identified. We report on a familial case of skeletal dysplasia with overlapping phenotype of mild CD and SPS, including defective ischio-pubic ossification, elongated femoral neck, hypoplastic patellae, and increased space between the first and the second toes (sandal gap). Direct sequencing analysis demonstrated a novel missense mutation (p.H169Q) within the coding region of the SOX9 gene and negative for TBX4 mutations. Functional analysis of the p.H169Q mutant revealed reduced but not fully abolished transactivation capacity of the mutated protein. Retained residual SOX9 function might contribute to an extremely mild CD phenotype in the present cases. © 2013 Wiley Periodicals, Inc.