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.

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.

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.

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.