Telescopic rodding in children: Technical progression from Dubow-Bailey to Fassier-Duval™.

Medical and surgical treatment of osteogenesis imperfecta has undergone two revolutions that improved quality of life and functional capacity: reduced bone absorption with the use of bisphosphonates, and improvement in internal fixation with the development of Dubow-Bailey then Fassier-Duval™ telescopic rodding. Telescopic intramedullary rodding in osteogenesis imperfecta and in other pathologies (congenital non-union and other congenital bone disorders) progressed with the replacement of the Dubow-Bailey rod by the telescopic Fassier-Duval™ rod. The aim of the present study was to provide an update on a technique that requires the utmost rigor and is not free of complications. Pitfalls and tips-and-tricks are presented in the light of our own experience.

Mandibular-pelvic-patellar syndrome is a novel PITX1-related disorder due to alteration of PITX1 transactivation ability.

PITX1 is a homeobox transcription factor essential for hindlimb morphogenesis. Two PITX1-related human disorders have been reported to date: PITX1 ectopic expression causes Liebenberg syndrome, characterized by malformation of upper limbs showing a "lower limb" appearance; PITX1 deletions or missense variation cause a syndromic picture including clubfoot, tibial hemimelia, and preaxial polydactyly. We report two novel PITX1 missense variants, altering PITX1 transactivation ability, in three individuals from two unrelated families showing a distinct recognizable autosomal dominant syndrome, including first branchial arch, pelvic, patellar, and male genital abnormalities. This syndrome shows striking similarities with the Pitx1-/- mouse model. A partial phenotypic overlap is also observed with Ischiocoxopodopatellar syndrome caused by TBX4 haploinsufficiency, and with the phenotypic spectrum caused by SOX9 anomalies, both genes being PITX1 downstream targets. Our study findings expand the spectrum of PITX1-related disorders and suggest a common pattern of developmental abnormalities in disorders of the PITX1-TBX4-SOX9 signaling pathway.

Skeletal impairment in Pierson syndrome: Is there a role for lamininß2 in bone physiology?

INTRODUCTION: Pierson syndrome is caused by a mutation of LAMB2, encoding for laminin ß2. Clinical phenotype is variable but usually associates congenital nephrotic syndrome (CNS) and ocular abnormalities. Neuromuscular impairment has also been described. METHODS: We report on a 15-year old girl, suffering from Pierson Syndrome, who developed severe bone deformations during puberty. This patient initially displayed CNS and microcoria, leading to the clinical diagnosis of Pierson syndrome. Genetic analysis revealed a truncating mutation and a splice site mutation of LAMB2. The patient received a renal transplantation (R-Tx) at the age of 3. After R-Tx, renal evolution was simple, the patient receiving low-dose corticosteroids, tacrolimus and mycophenolate mofetil. At the age of 12, bone deformations progressively appeared. At the time of bone impairment, renal function was subnormal (glomerular filtration rate using iohexol clearance 50mL/min per 1.73m2), and parameters of calcium/phosphate metabolism were normal (calcium 2.45mmol/L, phosphorus 1.30mmol/L, PTH 81ng/L, ALP 334U/L, 25OH-D 73nmol/L). Radiographs showed major deformations such as scoliosis, genu varum and diffuse epiphyseal abnormalities. A high resolution scanner (HR-pQCT) was performed, demonstrating a bone of "normal low" quantity and quality; major radial and cubital deformations were observed. Stainings of laminin ß2 were performed on bone and renal samples from the patient and healthy controls: as expected, laminin ß2 was expressed in the control kidney but not in the patient's renal tissue, and a similar pattern was observed in bone. CONCLUSION: This is the first case of skeletal impairment ever described in Pierson syndrome. Integrin α3ß1, receptor for laminin ß2, are found in podocytes and osteoblasts, and the observation of both the presence of laminin ß2 staining in healthy bone and its absence in the patient's bone raises the question of a potential role of laminin ß2 in bone physiology.

Arthrogryposis multiplex congenita. Long-term follow-up from birth until skeletal maturity.

PURPOSE: The aim of this retrospective long-term study was to review and present the effects of treatment for 11 children with arthrogryposis multiplex congenital, or amyoplasia, followed from birth until skeletal maturity. METHODS: We evaluated walking ability, age of beginning to walk, required ambulatory devices, age of independent walking and muscle strength. RESULTS: Our series showed babies with severe limb involvements without spine abnormalities. Despite the initial severity of involvement, nine patients finally became ambulators with flexion contracture of less than 20 degrees on hips and 15 degrees on knees, and six were independent walkers before the age of 2.5 years. The two non-ambulators presented severe scoliosis at skeletal maturity, which needed spinal fusion. CONCLUSION: We conclude that long-term ambulatory status at skeletal maturity is not correlated with the severity of condition at birth. A prognosis for ambulation at skeletal maturity will be done before 2.5 years of age. We believe that early aggressive management of children with severe arthrogryposis is warranted and justified.

Radial head dislocation and subluxation in osteogenesis imperfecta.

BACKGROUND: Upper limb deformity in children with osteogenesis imperfecta may substantially impair function. The aims of this retrospective work were to study the prevalence of radial head malalignment (dislocation or subluxation) in different types of osteogenesis imperfecta and to identify factors linked to it. METHODS: We assessed 489 upper limbs from 254 patients (with a mean age of 9.6 years and including 130 female patients) who had various types of osteogenesis imperfecta. Radiographs representing a single time-point for each patient were assessed for the presence and direction of radial head malalignment and associated abnormalities (dysplasia of the capitellum or of the radial head or neck, calcification of the interosseous membrane, or radioulnar synostosis). Deformations of the humerus, radius, and ulna were assessed with regard to location, direction, and magnitude. The forearm range of motion in pronation and supination and the hand grip force were measured in a subset of patients. RESULTS: We observed radial head dislocation or subluxation in forty-four and thirty-nine upper extremities, respectively. The frequency of radial head malalignment was significantly higher in type-V osteogenesis imperfecta (86%) than in the other types (0% to 29%) (p < 0.001). Dysplasia of the humeral capitellum, radial head, or radial neck was associated with malalignment in all types of osteogenesis imperfecta, with the exception of capitellum dysplasia in type V. Malalignment in type V was associated with calcification of the interosseous membrane, an abnormality that was specific for type V. In the other osteogenesis imperfecta types, malalignment was commonly linked with radial and ulnar deformation and was associated with decreased forearm range of motion in supination and pronation and a lower grip force. CONCLUSIONS: Radial head malalignment is common in osteogenesis imperfecta, especially in type V. Malalignment is associated with bowing characteristics and impaired function of the upper limb. These findings may provide support for surgical correction of radial and ulnar bowing in selected patients with osteogenesis imperfecta.