Fraser syndrome without cryptophthalmos: Two cases.

Fraser syndrome (MIM#219000) is an autosomal recessive disorder, characterized by the association of cryptophthtalmos, syndactyly of the four extremities, urinary tract abnormalities and laryngo-tracheal anomalies. This condition is due to homozygous or compound heterozygous mutations in the FRAS/FREM complex genes: FRAS1, FREM2 and GRIP1. Here we report two atypical cases of Fraser syndrome due to mutations in the FRAS1 gene without cryptophthalmos. The first proband had syndactyly of three extremities, bilateral nostril coloboma, dysplastic ears with bilateral conductive hearing loss, blepharophimosis and lacrimal duct abnormalities. FRAS1 sequencing identified two pathogenic compound heterozygous variants: a nonsense variant in exon 70 and a missense variant in exon 24. The second proband had membranous syndactyly of the four extremities, left renal agenesis, laryngeal and ano-rectal malformations, dysplastic ears and bilateral conductive hearing loss. FRAS1 sequencing identified a pathogenic homozygous variant in the last exon of the gene. This first description of molecularly confirmed cases with Fraser syndrome without cryptophthalmos could contribute to further delineation of the clinical spectrum of Fraser syndrome, especially for possible phenotypically milder cases. Larger cohorts are required to try to refer the hypothesis of genotype-phenotype correlation.

Imaging features of lower limb malformations above the foot.

Lower limb malformations are generally isolated or sporadic events. However, they are sometimes associated with other anomalies of the bones and/or viscera in patients with constitutional syndromes or disorders of the skeleton. This paper reviews the main imaging features of these abnormalities, which generally exhibit a broad spectrum. This paper focuses on several different bone malformations: proximal focal femoral deficiency, congenital short femur and femoral duplication for the femur, tibial hemimelia (aplasia/hypoplasia of the tibia) and congenital bowing for the tibia, fibular hemimelia (aplasia/hypoplasia) for the fibula, and aplasia, hypoplasia and congenital dislocation for the patella.

Unpredictability of hip behavior in Dyggve-Melchior-Clausen syndrome: a mid-term assessment of siblings.

Dyggve-Melchior-Clausen syndrome is a rare spondylo-epiphyseal disease, which almost constantly leads to both bilateral hip degeneration and dislocation. Few authors have reported to date the surgical management of this orthopaedic disorder. We present two new cases affecting siblings. One brother was treated by unilateral triple pelvic osteotomy combined with varus osteotomy of the proximal femur; the other was treated by bilateral Pemberton osteotomies with varus osteotomy of the proximal femur. At a respective 5-year and 3-year follow-up delay, both cases had evolved towards progressive subluxation recurrence along with severe hip degeneration. Based on both our experience and literature review, it seems that one should avoid operating these hips unless pain renders surgery mandatory. Total hip arthroplasty seems the only reliable surgical solution at the adult age and paediatric surgeons should keep in mind that previous femoral osteotomies will make it more challenging for adult orthopaedic surgeons to implant on a remodeled anatomy.

Congenital high scapula (Sprengel's deformity): four cases.

We report a series of four cases of congenital high scapula (or Sprengel's deformity) diagnosed and followed in our establishment. The main feature of this very rare congenital malformation of the pectoral girdle is an abnormally high, more or less dysmorphic scapula. A congenitally high scapula is often discovered in young children, when consequences for aesthetics, and sometimes functional difficulties, are brought to light. When surgical treatment is envisaged, imaging is recommended to diagnose a supernumerary structure, ossified (an omovertebral bone) or not (a fibrous and/or cartilaginous connection), extending from the scapula to the cervical spine. This needs to be resected. A CT scan is essential for detecting an omovertebral bone and the vertebral bone abnormalities that are often associated with it. MRI and ultrasound are very useful for assessing any fibrous and/or cartilaginous components. An ultrasound examination has the undeniable advantage of being quick and easy in these young children.

Progressive anterior vertebral fusion: a report of three cases.

We report a series of three cases of progressive anterior vertebral fusion diagnosed and monitored in our establishment. This very rare condition was discovered in young children while exploring a spinal deformity. With X-rays of the thoracolumbar spine it was possible to make a positive diagnosis and ensure follow-up. The radiographic semeiotics are characteristic and combine anterior pinching of the disc, well-delimited erosion of the anterior vertebral corners and anterior then posterior intervertebral ankylosis. MRI is very useful for assessing the extent of the intervertebral ankylosis and the condition of the residual discs, without irradiation. The condition develops over several months or years. Conservative treatment is usually sufficient.

Meningococcal purpura fulminans in children: I. Initial orthopedic management.

BACKGROUND: Purpura fulminans is a rare and extremely severe infection, mostly due to Neisseria meningitidis frequently causing early orthopedic lesions. Few studies have reported on the initial surgical management of acute purpura fulminans. The aim of this study is to look at the predictive factors in orthopedic outcome in light of the initial surgical management in children surviving initial resuscitation. METHODS: Nineteen patients referred to our institution between 1987 and 2005 were taken care of at the very beginning of the purpura fulminans. All cases were retrospectively reviewed so as to collect information on the total skin necrosis, vascular insufficiency, gangrene, and total duration of vasopressive treatment. RESULTS: All patients had multiorgan failure; only one never developed any skin necrosis or ischemia. Eighteen patients lost tissue, leading to 22 skin grafts, including two total skin grafts. There was only one graft failure. Thirteen patients were concerned by an amputation, representing, in total, 54 fingers, 36 toes, two transmetatarsal, and ten transtibial below-knee amputations, with a mean delay of 4 weeks after onset of the disease. Necrosis seems to affect mainly the lower limbs, but there is no predictive factor that impacted on the orthopedic outcome. We did not perform any fasciotomy or compartment pressure measurement to avoid non-perfusion worsening; nonetheless, our outcome in this series is comparable to existing series in the literature. V.A.C.(®) therapy could be promising regarding the management of skin necrosis in this particular context. While suffering from general multiorgan failure, great care should be observed not to miss any additional osseous or articular infection, as some patients also develop local osteitis and osteomyelitis that are often not diagnosed. CONCLUSIONS: We do not advocate very early surgery during the acute phase of purpura fulminans, as it does not change the orthopedic outcome in these children. By performing amputations and skin coverage some time after the acute phase, we obtained similar results to those found in the literature.

Meningococcal purpura fulminans in children. II: Late orthopedic sequelae management.

BACKGROUND: Purpura fulminans is a rare and extremely severe infection, mostly due to Neisseria meningitidis. Nineteen patients were followed up immediately after the initial multivisceral failure in order to diagnose late-onset orthopedic sequelae. We report our experience with these 19 patients, in light of our medical follow-up protocol and surgical management. MATERIALS AND METHODS: Nineteen patients were referred for acute purpura fulminans between 1987 and 2005 to our institution and followed up prospectively until the present. We collected information on all diagnosed orthopedic sequelae, all surgical procedures performed, and the actual orthopedic outcome. RESULTS: Fourteen patients developed at least one orthopedic sequel after a mean of 2 years delay, with a mean of 8.65 years follow-up (range 3-22 years). The most common presentation was lower limb physeal growth plate arrest in eight patients involving 18 growth plates, leading to five limb length discrepancies and 12 significant knee and/or ankle deviations. Patients were treated by completing epiphysiodesis in addition to limb lengthening and/or reaxation osteotomies, except for two patients, in which epiphysiolysis was performed. All outcomes are, to date, satisfactory, with both knee and ankle axes within the physiological range. Among the seven patients who underwent below-knee amputation, six needed stump revision because of skin conflict (4) or prosthetics misadaptation due to upper tibial varus (2). Regarding the upper limb, three patients presented with four cicatricial scar bands, one located on a ring finger, two at the first commissure, and one at the wrist (all were successfully treated by enlargement Z-plasties). Two patients developed hip avascular necrosis. CONCLUSION: It is important for children diagnosed with meningococcal purpura fulminans to be followed up closely starting from the very beginning by a pediatric orthopedic surgeon. It ensures that late-onset orthopedic sequelae will be diagnosed early. In accordance to the literature, this study highlights the high rate of lower limb epiphysiodesis, above all other types of sequelae. This study reports a possible link between purpura fulminans and avascular necrosis of the hip.

Oculo-dento-digital dysplasia: lack of genotype-phenotype correlation for GJA1 mutations and usefulness of neuro-imaging.

Oculo-dento-digital dysplasia (ODDD) is an autosomal dominant disorder with complete penetrance and high intra- and interfamilial phenotypic variability. The key features in this syndrome are microphthalmia, enamel hypoplasia and syndactyly of the 4th-5th fingers. ODDD is caused by mutations in the connexin 43 gene (GJA1). We report here four patients from three families with GJA1 mutations, one of them diagnosed prenatally. The three mutations (c.52T > C/p.Ser18Pro, c.689_690delTA/p.Tyr230CysfsX6, c.442C > G/p.Arg148Gly) have been reported once before. Two patients had white matter hypersignal anomalies, associated in one case with mental retardation, but asymptomatic in the other one, an observation that leads us to discuss systematic neuroradiological imaging for ODDD. One case has optic atrophy, another has hypospadias. The patient carrying a truncating mutation of Cx43 did not have palmoplantar keratoderma, in contradiction with the previously suggested genotype-phenotype correlation between truncating mutation and skin involvement.

[Genetics and orthopedics: genetic implications of congenital limb abnormalities]. / Génétique et orthopédie: gènes impliqués dans les malformations congénitales des membres.

Limb malformations are frequent. These malformations are isolated or associated with anomalies of other developmental fields and accurate diagnostic is essential for prognosis evaluation, treatment and genetic counseling. Animal embryology and molecular biology techniques, have given us a better understanding of the processes of growth and patterning of the limb buds. The key genes that are involved in these processes have been identified and their interactions recognized. Human genetics has been able to identify, or at least localize, several genes implicated in limb development. We here review the present knowledge on these genes and their mutations responsible for limb anomalies.