The Effectiveness of Growth Modulation Using Tension Band Plates in Children With Achondroplasia in Comparison to Children With Idiopathic Frontal Axial Deformities of the Knee.

BACKGROUND: Achondroplasia is the most common form of rhizomelic dwarfism. Aside from disproportionally short extremities, frontal knee malalignments are common. We assessed the effectiveness of guided growth via tension band plates in children with achondroplasia in comparison to patients with idiopathic knee deformities using radiography. METHODS: Twenty children with achondroplasia (8 valgus/31 varus knees) and 35 children with idiopathic knee malalignments (53 valgus/12 varus knees) which underwent temporary hemiepiphysiodesis at the distal femur and/or proximal tibia were retrospectively compared. Radiographic outcomes (mechanical lateral distal femoral angle, medial proximal tibial angle, and mechanical axis deviation) were compared before surgery and plate removal. Correction rates according to plate location were compared as change per implant duration and per growth in leg length. RESULTS: Achondroplasia patients were younger (9±2 vs.12±2 y), femoral and tibial growth rate was 43.3% and 48.5% lower and implant duration lasted longer: 36.9±8.9 months in valgus knees and 23.0±14.3 months in varus knees versus 13.4±7.9 months in idiopathic valgus and 11.7±4.6 months in idiopathic varus knees. Significant improvements in joint orientation angles and mechanical axis deviation were achieved but femoral and tibial plates achieved slower correction per months in achondroplasia (P≤0.031). When normalized to bone growth, the rate of correction in joint orientation angles was no longer significantly different for the femur (P=0.241), with a trend for slower correction in the tibia (P=0.066). The corrections in MAD per leg growth (mm/mm) remained smaller (P=0.001). In achondroplasia, older age correlated with slower MAD correction (r=-0.36, P=0.022), femoral plates corrected faster than tibial (P=0.024) and treatment of valgus was less successful than varus involving longer treatments (P=0.009). More complications occurred in achondroplastic knees (P=0.012). CONCLUSIONS: Skeletally immature patients with achondroplasia can benefit from growth modulations, but they need longer treatments and face more complications. Their slower growth does not solely determine the more tenacious success. LEVEL OF EVIDENCE: Therapeutic Level III-case-control study.

Relationship between kinematic gait quality and caregiver-reported everyday mobility in children and youth with spastic Cerebral Palsy.

BACKGROUND: 3D gait analysis (3DGA) is a common assessment in Cerebral Palsy (CP) to quantify the extent of movement abnormalities. Yet, 3DGA is performed in laboratories and may thus be of debatable significance to everyday life. AIM: The aim was to assess the relationship between kinematic gait abnormality and everyday mobility in ambulatory children and youth with spastic CP. METHODS: 73 paediatric and juvenile patients with uni- or bilateral spastic CP (N = 21 USCP, N = 52, BSCP, age: 4-20 y, GMFCS I-III) underwent a 3DGA, while the MobQues47 Questionnaire quantified caregiver-reported mobility. We calculated the Gait Profile Score (GPS), a metric that summarizes how far the lower limb joint angles during walking deviate from those of matched controls. RESULTS: The GPS correlated well with indoor and outdoor mobility (rho = -0.69 and -0.70, both p < 0.001) and the relationships were not significantly different for USCP and BSCP. Still, mobility was lower in BSCP (p < 0.001) and more compromised outdoors (p = 0.002). Indoor mobility could be predicted by walking speed, GPS and age (adj. R2 = 0.62). Outdoor mobility was best predicted by walking speed and GPS (adj. R2 = 0.60). The additive explained variance by the GPS was even higher outdoors than indoors (17.1% vs. 11.4%). CONCLUSIONS: Measuring movement deviations with 3DGA seems equally meaningful in uni- and bilaterally affected children and has considerable relevance for real-life ambulation, particurlarly outdoors, where children with spastic CP typically face greater difficulties. Therapeutic strategies that achieve faster walking and reduction of kinematic deviations may increase outdoor mobility.

Self-perceived foot function and pain in children and adolescents with flexible flatfeet - Relationship between dynamic pedobarography and the foot function index.

BACKGROUND: There is considerable debate as to which parameters to include in the assessment of paediatric flatfeet. Dynamic pedobarography is an objective, dynamic method to measure foot function. Information about its associations to patient-reported measures may help to focus on the most relevant parameters. RESEARCH QUESTION: What is the association between the Foot Function Index and pedobarographic assessments in flatfeet of children and adolescents? METHODS: A consecutive clinical case series of 51 participants with idiopathic flexible flatfeet aged 7-17 years underwent barefooted pedobarography during gait and completed the Foot Function Index Questionnaire. Pedobarographic data categorized into values related to area, peak pressure and force with respect to the hind-, mid- and forefoot were extracted. To test the associations between the Foot Function Index and pedobarographic assessments, bivariate partial correlations were tested and contact times served as co-variate. RESULTS: Several significant associations between peak pressure or forces beneath the hindfoot, midfoot and hallux to self-perceived function were found (|rho| = 0.28-.46, P < 0.05). In particular, reduced peak forces and pressures underneath the hindfoot and hallux, a lateral shift (smaller medio-lateral ratios) of hindfoot pressure and force and a medial shift (larger medio-lateral ratios) of midfoot pressure seem to be negatively associated with foot-related disability. Overall, less evidence was noted for associations to pain scores. Area related outcomes (including the arch index) contained no information for function while a larger BMI was the strongest thread for disability (rho = 0.42, P = 0.002) and pain (rho = 0.31, P = 0.027). SIGNIFICANCE: When using pedobarography for the assessment of flexible flatfeet of children and adolescents, less attention should be paid to area related measurements which do not provide information about self-perceived function or disability. Instead, peak pressures or forces in the hind- or midfoot or beneath the hallux may be focussed. Weight reductions are potentially an effective strategy to reduce or prevent symptoms.

Phenotype and genotype in patients with Larsen syndrome: clinical homogeneity and allelic heterogeneity in seven patients.

BACKGROUND: Larsen syndrome is an autosomal dominant skeletal dysplasia characterized by large joint dislocations and craniofacial dysmorphism. It is caused by missense or small in-frame deletions in the FLNB gene. To further characterize the phenotype and the mutation spectrum of this condition, we investigated seven probands, five sporadic individuals and a mother-son-duo with Larsen syndrome. METHODS: The seven patients from six unrelated families were clinically and radiologically evaluated. All patients were screened for mutations in selected exons and exon-intron boundaries of the FLNB gene by Sanger sequencing. FLNB transcript analysis was carried out in one patient to analyse the effect of the sequence variant on pre-mRNA splicing. RESULTS: All patients exhibited typical facial features and joint dislocations. Contrary to the widely described advanced carpal ossification, we noted delay in two patients. We identified the five novel mutations c.4927G A/p.(Gly1643Ser), c.4876G > T / p.(Gly1626Trp), c.4664G > A / p.(Gly1555Asp), c.2055G > C / p.Gln685delins10 and c.5021C > T / p.(Ala1674Val) as well as a frequently observed mutation in Larsen syndrome [c.5164G > A/p.(Gly1722Ser)] in the hotspot regions. FLNB transcript analysis of the c.2055G > C variant revealed insertion of 27 bp intronic sequence between exon 13 and 14 which gives rise to in-frame deletion of glutamine 685 and insertion of ten novel amino acid residues (p.Gln685delins10). CONCLUSIONS: All seven individuals with Larsen syndrome had a uniform clinical phenotype except for delayed carpal ossification in two of them. Our study reveals five novel FLNB mutations and confirms immunoglobulin-like (Ig) repeats 14 and 15 as major hotspot regions. The p.Gln685delins10 mutation is the first Larsen syndrome-associated alteration located in Ig repeat 5. All mutations reported so far leave the filamin B protein intact in accordance with a gain-of-function effect. Our findings underscore the characteristic clinical picture of FLNB-associated Larsen syndrome and add Ig repeat 5 to the filamin B domains affected by the clustered mutations.

Femoral facial syndrome associated with a de novo complex chromosome 2q37 rearrangement.

The femoral facial syndrome (FFS) is a rare congenital anomaly syndrome characterized by bilateral femoral hypoplasia and facial dysmorphism. The etiology of FFS is currently unknown but maternal/gestational diabetes has been proposed as a strong risk factor for syndromic femoral hypoplasia. In affected children born to non-diabetic mothers, a genetic contribution to FFS is suspected; however, no chromosomal anomalies or gene mutations have been identified so far. Here, we report on a girl with FFS and a de novo complex chromosome rearrangement of terminal chromosome 2q37.2. Radiographs of the pelvis and lower limbs showed bilateral shortening and bowing of the femur and radiographs of hands and feet revealed a brachydactyly type E (BDE). Using high resolution array-CGH, qPCR, and FISH, we detected a ~1.9 Mb duplication in the chromosomal region 2q37.2 and a ~5.4 Mb deletion on chromosome 2q37.3 that were absent in the parents. The duplication contains six genes and the deletion encompasses 68 genes; the latter has previously been shown to cause BDE (through haploinsufficiency for HDAC4) but not femoral hypoplasia. Therefore, we propose that the duplication 2q37.2 could be causative for the femur phenotype. To the best of our knowledge, our report is the first to propose a genetic cause in a case of FFS.

Dega osteotomy for the management of developmental dysplasia of the hip in children aged 2-8 years: results of 58 consecutive osteotomies after 13-25 years of follow-up.

PURPOSE: Developmental dysplasia of the hip (DDH) is a term used to cover a broad spectrum of anomalies ranging from mild dysplasia to high-riding dislocations. We report the management of DDH in children using the Dega osteotomy and their long-term follow-up. METHODS: Fifty-eight hips from 48 children younger than 8 years treated using the Dega osteotomy between January 1988 and October 2000 were included in this multcenter study. Both prospective (41 hips) and retrospective (17 hips) cases were included, and follow-up was for a minimum of 13 years. Radiographs were made preoperatively, immediately postoperatively, after 6 weeks or at removal of the spica cast if any, at 6-month intervals and/or as indicated for 3 years postoperatively and then on annual basis until the last follow-up. A single-cut computed tomographic scan was performed for all prospective patients. Special attention was paid to the predictive measures of hip arthrosis and the survival of the hip after Dega osteotomy. RESULTS: The final clinical outcome was favorable in 44 hips (75.9 %). Eleven hips needed a second surgery (acetabuloplasty and/or arthroplasty) during the follow-up period. CONCLUSIONS: In our pediatric patient population the Dega osteotomy proved to be an adequate measure for the management of this complex condition. The worst complication was avascular necrosis, and all of the affected hips ended with failure (pain, another surgery, or both).