Novel pathogenic variants and quantitative phenotypic analyses of Robinow syndrome: WNT signaling perturbation and phenotypic variability.

Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A). RS is characterized by skeletal dysplasia and distinctive facial and physical characteristics. To further explore the genetic heterogeneity, paralog contribution, and phenotypic variability of RS, we investigated a cohort of 22 individuals clinically diagnosed with RS from 18 unrelated families. Pathogenic or likely pathogenic variants in genes associated with RS or RS phenocopies were identified in all 22 individuals, including the first variant to be reported in DVL2. We retrospectively collected medical records of 16 individuals from this cohort and extracted clinical descriptions from 52 previously published cases. We performed Human Phenotype Ontology (HPO) based quantitative phenotypic analyses to dissect allele-specific phenotypic differences. Individuals with FZD2 variants clustered into two groups with demonstrable phenotypic differences between those with missense and truncating alleles. Probands with biallelic NXN variants clustered together with the majority of probands carrying DVL1, DVL2, and DVL3 variants, demonstrating no phenotypic distinction between the NXN-autosomal recessive and dominant forms of RS. While phenotypically similar diseases on the RS differential matched through HPO analysis, clustering using phenotype similarity score placed RS-associated phenotypes in a unique cluster containing WNT5A, FZD2, and ROR2 apart from non-RS-associated paralogs. Through human phenotype analyses of this RS cohort and OMIM clinical synopses of Mendelian disease, this study begins to tease apart specific biologic roles for non-canonical WNT-pathway proteins.

What is a good result after clubfoot treatment? A Delphi-based consensus on success by regional clubfoot trainers from across Africa.

BACKGROUND: Congenital talipes equino-varus (CTEV), also known as clubfoot, is one of the most common congenital musculoskeletal malformations. Despite this, considerable variation exists in the measurement of deformity correction and outcome evaluation. This study aims to determine the criteria for successful clubfoot correction using the Ponseti technique in low resource settings through Africa. METHODS: Using the Delphi method, 18 experienced clubfoot practitioners and trainers from ten countries in Africa ranked the importance of 22 criteria to define an 'acceptable or good clubfoot correction' at the end of bracing with the Ponseti technique. A 10cm visual analogue scale was used. They repeated the rating with the results of the mean scores and standard deviation of the first test provided. The consistency among trainers was determined with the intra-class correlation coefficient (ICC). From the original 22 criteria, ten criteria with a mean score >7 and SD <2 were identified and were rated through a second Delphi round by 17 different clubfoot treatment trainers from 11 countries in Africa. The final definition consisted of all statements that achieved strong agreement, a mean score of >9 and SD<1.5. RESULTS: The consensus definition of a successfully treated clubfoot includes: (1) a plantigrade foot, (2) the ability to wear a normal shoe, (3) no pain, and (4) the parent is satisfied. Participants demonstrated good consistency in rating these final criteria (ICC 0.88; 0.74,0.97). CONCLUSIONS: The consistency of Ponseti technique trainers from Africa in rating criteria for a successful outcome of clubfoot management was good. The consensus definition includes basic physical assessment, footwear use, pain and parent satisfaction.

What Is the Early/Mid-term Survivorship and Functional Outcome After Bernese Periacetabular Osteotomy in a Pediatric Surgeon Practice?

BACKGROUND: The Bernese periacetabular osteotomy (PAO) is a recognized joint-preserving procedure. Achieving joint stability without creating impingement is important, but the orientation target that best balances these sometimes competing goals has not yet been clearly defined. Moreover, the learning curve of this challenging procedure has not been described. QUESTIONS/PURPOSES: The purposes of this study were (1) to determine the 10-year survivorship and functional outcome after Bernese PAO in a single-surgeon series; (2) to review which patient, surgical, and radiographic factors might predict outcome after the procedure; and (3) to define the learning curve for target acetabular correction. METHODS: The first 68 PAOs performed for symptomatic hip dysplasia were retrospectively evaluated. None have been lost to followup with followup less than 2 years. Endpoints for the lost to followup (n = 2) are at the time of when last seen. During the study period, the same surgeon performed 562 pelvic osteotomies (including Salter, Pemberton, Dega and Chiari) and 64 shelf acetabuloplasties. Bernese PAO was used only for symptomatic dysplasia (center-edge angle < 25° and nonhorizontal acetabular roof) in developmentally mature hips without evidence of major joint incongruence or subluxation. Most patients were female (n = 49 [60 hips, 88%]); mean age at operation was 25 years (SD 7). Sixteen hips had previous hip procedures. The study's mean followup was 8 years (range, 2-18 years). Patient-reported functional outcome was obtained using the WOMAC score (best-worst: 0-96). Radiographic parameters of dysplasia (acetabular index [AI], center-edge angle [CEA], congruency, Tönnis grade, and joint space) were evaluated from preoperative and postoperative radiographs using computer software. RESULTS: The 10-year survival rate was 93% (95% confidence interval [CI], 82%-100%); four patients underwent further surgery to the hip in the study period. The mean WOMAC was 12 (range, 0-54). Factors that influenced survival included joint congruency (100% versus 78%; 95% CI, 61%-96%; p = 0.03) and acetabular orientation correction achieved (AIpostoperative < 15° [100% versus 65%; 95% CI, 43-88; p < 0.001] and CEApostoperative 20° to 40° [100% versus 71.9%; 52.8-100; p < 0.001]). Better WOMAC scores were seen if postoperative AI < 15° (7 versus 25, p = 0.005) and CEA between 20° and 40° (7 versus 23, p = 0.005) were achieved. The chances of obtaining acetabular correction within this range improved after the 20(th) procedure (30% versus 70%, p = 0.008). CONCLUSIONS: This study reports excellent results after Bernese PAO in the hands of an experienced pediatric hip surgeon. We advocate cautious correction of the acetabular fragment. Future studies should concentrate on how to determine what the optimal target is and how to achieve it intraoperatively, minimizing the learning curve associated with it. LEVEL OF EVIDENCE: Level III, therapeutic study.

The outcome of patients with hinge abduction in severe Perthes disease treated by shelf acetabuloplasty.

BACKGROUND: The management of patients with Perthes disease remains controversial. In children with hinge abduction and the potential for remodeling, we have performed a shelf acetabuloplasty, in an effort to contain the hip and allow remodeling. We report our medium-term results in a consecutive series of 27 children with severe Perthes disease and arthrographically proven hinge abduction. This is the first report in the English literature to look specifically at the results of treating patients with hinge abduction in severe Perthes disease by shelf acetabuloplasty. METHODS: Twenty-seven consecutive children with unilateral Perthes disease and arthrographically proven hinge abduction were treated with a shelf acetabuloplasty. These patients have been prospectively reviewed with a clinical examination and radiographic assessment including Catterall, Salter Thompson, and Herring's lateral pillar classification. Radiological measurements included percentage acetabular cover, medial joint space, and femoral head size ratio. RESULTS: The mean postoperative follow-up was 62 months (range, 26-125 months). All patients were Catterall grade III or IV and lateral pillar grade B or C and had arthrographically proven hinge abduction at the time of surgery. At final follow-up, 14 hips were Stulberg grades 1 and 2; 10 hips, grade 3; and 3 hips, grades 4 and 5. The medial joint space decreased from a preoperative ratio of 1.9 to 1.4 (P = 0.002), and the percentage acetabular cover increased from 81% preoperatively to 97% postoperatively (P < 0.001). CONCLUSION: These results suggest overall good outcomes from a group of patients with severe Perthes disease as measured by the Stulberg grading when compared with historical controls. We suggest that shelf acetabuloplasty is a straight forward surgical procedure with good medium-term results in patients with severe Perthes disease who have proven hinge abduction preoperatively. LEVEL OF EVIDENCE: Level IV case series.

Hip arthrography in the assessment of children with developmental dysplasia of the hip and Perthes' disease.

In our unit, children with developmental dysplasia of the hip or Perthes' disease, for whom an operation is considered, undergo examination under anaesthetic and a hip arthrogram. This prospective study assessed whether the arthrogram modified treatment and analysed the reliability of its interpretation. All children undergoing a hip arthrogram for developmental dysplasia of the hip and Perthes' disease over a 12-month period were included. Treatment plans before and after the arthrogram were compared for each of the three children's consultants. The preoperative and arthrographic appearances were blindly reviewed to monitor reproducibility. Twenty-one patients with developmental dysplasia of the hip and 19 with Perthes' disease were included. The treatment plan was modified in 12 of the 21 (57.1%) patients with developmental dysplasia of the hip as a consequence of the arthrogram and six of the 19 patients (31.6%) with Perthes' disease. Intraobserver consultant agreement was high but interobserver agreement was only moderate. Static and dynamic arthrography helps decision-making in patients with developmental dysplasia of the hip and Perthes' disease.

The classification of congenital talipes equinovarus.

e have assessed the reliability of four classification systems for club foot. Four observers evaluated nine children (18 feet) at different stages in the first six months of life, a total of 180 examinations. Each observer independently assessed all feet according to the classification systems described by Catterall, Diméglio et al, Harrold and Walker, and Ponseti and Smoley. The variation between observers was assessed using the kappa test which for no more agreement than chance has a value of 0, and for complete agreement between observers a value of 1. The kappa values varied between 0.14 and 0.77 depending on which classification system was used. The system of Diméglio et al was found to have the greatest reliability. Our findings suggest that current classification systems for the analysis of congenital talipes equinovarus are not entirely satisfactory.