Management of Thoracic Insufficiency Syndrome in Patients With Jeune Syndrome Using the 70 mm Radius Vertical Expandable Prosthetic Titanium Rib.

BACKGROUND: Jeune syndrome (JS) often results in lethal thoracic insufficiency syndrome. Since 1991, vertical expandable prosthetic titanium rib Dynamic PosteroLateral Expansion Thoracoplasty was used at our institution for treatment of JS. This study assesses the safety and efficacy of this procedure. METHODS: Twenty-four JS patients were treated, 2 lost to follow-up, 17 with a minimum of 2-year follow-up retrospectively reviewed for clinical course: Assisted Ventilation Rate, respiratory rate, capillary blood gases, pulmonary function testings, and complications. Upright anteroposterior/lateral radiographs were measured for Cobb angle, kyphosis, lordosis, thoracic width, and thoracic/lumbar spinal height. Computed tomography scan lung volumes were obtained in 12 patients. RESULTS: Mean age at initial implant was 23 months (7 to 62 mo) with an average 8.4 years (2.3 to 15.6 y) of follow-up. Average chest width increased from 121 to 168 mm at follow-up (P<0.001). Preoperatively, 7/17 (41%) patients had scoliosis. The remainder developed scoliosis during treatment, 8 requiring additional implants. Thoracic and lumbar spinal height was normal preoperatively and stayed normal during treatment. Thoracic kyphosis/lumbar lordosis was stable. Average computed tomography scan total lung volumes increased 484 to 740 mm3 (P<0.001), and Assisted Ventilation Rate status tended to improve (P=0.07). Average forced vital capacity was 34% predicted at first test and 27% predicted at last follow-up. Early demise after surgery was common with multisystem disease. Mean respiratory rate decreased from 35 to 24 bpm at last follow-up (P<0.05). Survival rate of the 22 patients was 68%. Migration of the rib cradles/titanium slings occurred in 12 patients, superficial infections in 5 patients, deep infections in 4 patients, and wound dehiscence in 5 patients. Infection rate was 4.6% per procedure. CONCLUSIONS: The survival rate in JS with surgery was nearly 70% (compared with 70% to 80% mortality without treatment) with less ventilator dependence. Both C1 stenosis and scoliosis are common in JS. Spinal height in JS is normal. Complications are frequent, but tolerable in view of the clinical gains and increase in survival.

Cardio-facio-cutaneous syndrome: clinical features, diagnosis, and management guidelines.

Cardio-facio-cutaneous syndrome (CFC) is one of the RASopathies that bears many clinical features in common with the other syndromes in this group, most notably Noonan syndrome and Costello syndrome. CFC is genetically heterogeneous and caused by gene mutations in the Ras/mitogen-activated protein kinase pathway. The major features of CFC include characteristic craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. It is essential that this condition be differentiated from other RASopathies, as a correct diagnosis is important for appropriate medical management and determining recurrence risk. Children and adults with CFC require multidisciplinary care from specialists, and the need for comprehensive management has been apparent to families and health care professionals caring for affected individuals. To address this need, CFC International, a nonprofit family support organization that provides a forum for information, support, and facilitation of research in basic medical and social issues affecting individuals with CFC, organized a consensus conference. Experts in multiple medical specialties provided clinical management guidelines for pediatricians and other care providers. These guidelines will assist in an accurate diagnosis of individuals with CFC, provide best practice recommendations, and facilitate long-term medical care.

Peripheral muscle weakness in RASopathies.

INTRODUCTION: RASopathies are a group of genetic conditions due to alterations of the Ras/MAPK pathway. Neurocutaneous findings are hallmark features of the RASopathies, but musculoskeletal abnormalities are also frequent. The objective was to evaluate handgrip strength in the RASopathies. METHODS: Individuals with RASopathies (e.g., Noonan syndrome, Costello syndrome, cardio-facio-cutaneous [CFC] syndrome, and neurofibromatosis type 1 [NF1]) and healthy controls were evaluated. Two methods of handgrip strength were tested: GRIP-D Takei Hand Grip Dynamometer and the Martin vigorimeter. A general linear model was fitted to compare average strength among the groups, controlling for confounders such as age, gender, height, and weight. RESULTS: Takei dynamometer: handgrip strength was decreased in each of the syndromes compared with controls. Decreased handgrip strength compared with sibling controls was also seen with the Martin vigorimeter (P < 0.0001). CONCLUSIONS: Handgrip strength is decreased in the RASopathies. The etiology of the reduced muscle force is unknown, but likely multifactorial.

Shelf and/or reduction and containment surgery.

Hinge abduction occurs early in the fragmentation stage of Legg-Calvé-Perthes disease and should be suspected when abduction and internal rotation are lost. It can be confirmed by an AP radiograph in abduction and internal rotation in which the ossific nucleus is not covered by the acetabulum. An arthrogram can then yield greater information regarding the reversibility of the hinge abduction. Hinge abduction should be considered a contraindication to containment by redirectional pelvic or femoral varus osteotomy. However, good results have been reported with acetabular augmentation via shelf procedures or Chiari osteotomies. Valgus femoral osteotomies have also been beneficial in the treatment of the Legg-Calvé-Perthes hip with hinge abduction.

Orthopaedic conditions in Ras/MAPK related disorders.

BACKGROUND: The RAS/MAPK disorders [Noonan syndrome, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, and Leopard syndrome] are heterogenous conditions with phenotypic overlap. Their orthopaedic manifestations are not well defined, and their phenotypic similarity makes differentiating them difficult. METHODS: We prospectively evaluated 60 individuals: 26 with Noonan syndrome, 32 with CFC syndrome, and 2 with Costello syndrome. Each individual underwent a structured orthopaedic history and physical evaluation by an orthopaedic surgeon, and a syndromic evaluation by a geneticist. RESULTS: All groups had a high prevalence of scoliosis (8/26 Noonan syndrome, 8/32 CFC syndrome, and 1/2 Costello). Those with Noonan syndrome or CFC syndrome had a high instance of serious cervical spine disorders, including cervical stenosis, Arnold-Chiari malformation, and syringomyelia in the Noonan syndrome individuals and hydrocephalus, cervical stenosis, torticollis, and Arnold-Chiari in the CFC syndrome individuals. Noonan syndrome manifestations included chronic pain (n=21), pes planus (n=11), pes cavus (n=5), hip contractures (n=5), hand dysfunction (n=3), and hip dysplasia (n=2). Manifestations of CFC syndrome included pes planovalgus (n=20), knee flexion contractures (n=7), hip dysplasia (n=5), elbow flexion contractures (n=4), pedal calluses (n=4), toe crowding (n=4), and hip contractures (n=4). Individuals with Costello syndrome had shorter stature than the other groups and were prone to have hand contractures. CONCLUSIONS: Orthopaedic manifestations are frequent and diverse in Ras/MAPK disorders and can be used in phenotypic differentiation between these disorders. LEVEL OF EVIDENCE: II.

Can VEPTR(®) control progression of early-onset kyphoscoliosis? A cohort study of VEPTR(®) patients with severe kyphoscoliosis.

BACKGROUND: Kyphoscoliosis is considered a relative contraindication to treatment with the Vertical Expandable Prosthetic Titanium Rib (VEPTR(®); Synthes Inc, Paoli, PA). Nevertheless, patients do present with early-onset kyphoscoliosis and thoracic insufficiency syndrome, and no suitable alternative treatments are currently available. However, it is unclear whether VEPTR(®) is reasonable for treating patients with kyphoscoliosis. QUESTIONS/PURPOSES: We determined whether VEPTR(®) controls progression in patients with kyphoscoliosis and, if so, what methods might be used to improve control of deformity progression in these patients. PATIENTS AND METHODS: We retrospectively reviewed 14 patients who had VEPTR(®) treatment of early-onset kyphoscoliosis. Degrees of kyphosis and scoliosis before, during, and after treatment were measured, and levels of instrumentation, thoracic dimensions, and complications were recorded. Minimum followup was 1.7 years (average, 5.8 years; range, 1.7-12.8 years). RESULTS: While scoliosis was stabilized, kyphosis increased a mean of 22° at last followup. Supple kyphosis became rigid during treatment. Proximal cradle cutout was a recurring problem. Distal anchors placed too proximally had inadequate lever arms to control kyphosis. CONCLUSIONS: Progression of kyphosis can be minimized during VEPTR(®) treatment by early extension of the construct to the second ribs bilaterally, distal extension of hybrid constructs to the pelvis, use of bilateral hybrid VEPTR(®) implants, and use of redesigned VEPTR(®) constructs that enhance fixation at the upper end. While our early results suggest these devices control progression of kyphosis, longer followup with more patients will be required to confirm the concept in these patients.