Mutations in EDARADD account for a small proportion of hypohidrotic ectodermal dysplasia cases.

BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is characterized by abnormal development of the eccrine sweat glands, hair and teeth. The X-linked form of the disease, caused by mutations in the EDA gene, represents the majority of HED cases. Autosomal dominant and recessive forms occasionally occur and result from mutations in at least two other genes: EDAR and EDARADD. EDARADD interacts with the TAB2/TRAF6/TAK1 complex, which is necessary for NF-kappaB activation by EDAR. OBJECTIVES: To determine frequency of EDARADD, TRAF6, TAB2 and TAK1 mutations in HED. MATERIALS AND METHODS: We have screened 28 familial or sporadic HED cases with no mutations in the EDA and EDAR genes for EDARADD, TRAF6, TAB2 and TAK1 mutations. RESULTS: We identified one EDARADD 6-bp homozygous in-frame deletion (c.402-407del, p.Thr135-Val136del) in a patient born to consanguineous parents. Functional studies showed that the p.Thr135-Val136del impaired the EDAR-EDARADD interaction and then severely inhibited NF-kappaB activity. In the remaining 27 patients, we failed to find causative mutations in EDARADD, or in TRAF6, TAB2 or TAK1. CONCLUSIONS: Our study demonstrates that EDARADD mutations are not a frequent cause of HED, while mutations in TRAF6, TAB2 and TAK1 may not be implicated in this disease.

[Dental extractions in children with congenital coagulation disorders: therapeutic protocol and results]. / Extractions dentaires chez l'enfant présentant une maladie hémorragique constitutionnelle: protocole thérapeutique et résultats.

INTRODUCTION: We report the results of our 10-year experience with a protocol of local hemostasis specifically elaborated for children with congenital bleeding disorders. MATERIAL AND METHOD: Sixty-four dental extractions procedures were performed in 37 children. Local hemostasis was achieved with the CO2 laser at the site of extraction previously filled with regenerated oxidized cellulose. The site of extraction was then protected with thermomolded splint. The replacement therapy (hemostasis factor concentrates, platelet concentrates) was coordinated by the hematologist and restricted as much as possible. RESULTS: 160 decidual teeth and 23 permanent teeth were extracted. None of the children with minor bleeding deficiency received replacement therapy. Ten post-operative bleedings were recorded but none was considered severe. DISCUSSION: This protocol characterized by the use of CO2 laser for the hemostasis gave satisfaction in children. The rare and minor post-operative bleedings could be explained by multiple extractions, local infection and/or children's anxiety. This strategy requires a close cooperation between the stomatologist and the hematologist in order to determine the optimal therapeutic management.

[Cleft of the lower lip, mandible and sternum. A case report and review of the literature]. / Fente labiomandibulaire et sternale. A propos d'un cas et revue de la littérature.

The Authors report a case of cleft interesting the lower lip and mandible with a sternal cleft. This association is exceptional, it was described in three world cases to this day. At this occasion, a review of the literature is realized, in particular concerning the associated malformatives anomalies and the therapeutic behaviour. It seems to us indispensable to realize an early reconstruction, specially bone correction, and to collaborate with a multidisciplinary team to obtain a good result and a better social incorporation of the child.

Mutational spectrum of the ED1 gene in X-linked hypohidrotic ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is the most common form of the ectodermal dysplasias characterised by an abnormal development of eccrine sweat glands, hair and teeth. The ED1 gene responsible for the disorder undergoes extensive alternative splicing and to date few studies have concerned the full length transcript. We screened 52 unrelated families or sporadic cases for mutation in the full coding sequence of this gene. SSCA analysis or direct sequencing allowed identification of mutations in 34 families: one initiation defect, twenty-two missenses, two nonsense, eight insertions or deletions, and a large deletion encompassing all the ED1 gene. Fourteen of these mutations have not been previously described, including five missenses. One third of identified mutations were localised in codons 155 and 156, affecting CpG dinucleotides and nine of them correspond to the R156H missense. Hypothesis of a founder effect has been ruled out by haplotype analysis of flanking microsatellites. These recurrent mutations indicate the functional importance of the positively charged domain of the protein. Including our data, there are now 56 different mutations reported in 85 independent patients, that we have tabulated. Review of clinical features in the present series of affected males and female carriers showed no obvious correlation between the type of mutations, the phenotype and its severity. The X-chromosome pattern of inactivation in leucocytes showed little correlation with expressivity of the disease in female carriers. Finally this study is useful for functional studies of the protein and to define a diagnostic strategy for mutation screening of the ED1 gene.

[Benign tumors and pseudotumor of the maxilla in children]. / Tumeurs bénignes et pseudo-tumeurs des maxillaires de l'enfant.

The underlying causes in series of benign tumours and pseudo-tumours and cysts of the maxillary bone observed in children over a ten-year period in the Saint-Vincent-de-Paul Hospital in Paris are reported. Besides the frequently encountered odontogenic cysts, most cases involved aneurysmal cysts and benign odontogenic tumours, as well as rare tumours including a hydatic cyst. Several lesions were discovered on a panoramic X ray performed for orthodontal survey.

[Permanent constriction of the jaws in children: 3 cases with extra-articular etiology]. / Les constrictions permanentes des mâchoires de l'enfant. Trois cas d'étiologie extra-articulaire.

Three cases of permanent constriction of the jaw are reported. One was a sequela after a noma, the second occurred in a child with arthrogryposis and the third was an inborn malformation. Each case raised specific problems for diagnosis and treatment. Mechanicotherapy is essential postoperatively and requires a specific electric apparatus to mobilize the joint.

[Hemangiopericytoma of the infra-temporal fossa. Apropos of a clinical case]. / Hémangiopéricytome de la fosse infra-temporale. A propos d'un cas clinique.

We observed the case of a young woman with haemangiopericytoma in the subtemporal fossa. Diagnosis problems and the access route were discussed. Good exposure was achieved at the price of minor aesthetic and functional impairment. The prognosis of these potentially malignant tumors is uncertain.

Identification of genes overexpressed in tumors through preferential expression screening in trophoblasts.

Early trophoblastic cells share several features with neoplastic cells. Based on that observation, we attempted to identify genes overexpressed in tumors by analyzing genes preferentially expressed in trophoblasts. A subtracted library enriched in complementary DNA from early cytotrophoblasts was constructed, and the expression level of selected recombinants was analyzed on a large panel of normal and tumor tissues. The library was prepared using a polymerase chain reaction-based complementary DNA subtraction method with 6-week amenorrhea cytotrophoblast endoplasmic reticulum-bound RNA as target, and a mixture of complementary DNA prepared from terminal placenta and activated T-lymphocytes as driver. Two rounds of screening were performed to isolate clones preferentially expressed in early placenta. From a total number of recombinant clones estimated at 32,000 in the subtracted library, 594 inserts were analyzed by Southern blot and 21 sequences were isolated as corresponding to genes highly expressed in early placenta. Eleven encoded known molecules, such as carcinoembryonic antigen, human chorionic gonadotropin, and mitochondrial rRNAs. Ten sequences represented novel genes. Northern blot analysis confirmed that most of these genes were preferentially expressed in early trophoblast in comparison to terminal placenta. Three clones that gave detectable hybridization signals on total RNA were extensively studied and were found to be overexpressed in various tumors. Two of these clones, designated B9 and E4, were later identified as corresponding to genes coding for the putative ribosomal protein S18 and the bifunctional enzyme ADE2H1 involved in purine biosynthesis, respectively. Expression of the third clone, E9, was increased up to 10-fold in breast cancer tissues in comparison with normal counterparts. Present results confirm that many genes expressed in the trophoblast are overexpressed in malignant cells. This approach could provide a general targeted method for the identification of genes overexpressed in various neoplastic cell types.

Type II collagen defect in two sibs with the Goldblatt syndrome, a chondrodysplasia with dentinogenesis imperfecta, and joint laxity.

We report on a syndrome of spondylo-epimetaphyseal dysplasia, dentinogenesis imperfecta, and ligamentous hyperextensibility in two sibs born to nonconsanguineous parents. This chondrodysplasia was characterized by severe shortness of stature and an osteoporosis without fractures. Electron microscopic examination of the cartilage documented large vacuoles of dilated rough endoplasmic reticulum within the cytoplasm of chondrocytes. Gel electrophoresis of pepsin-soluble collagen extracted from cartilage demonstrated the presence of type II collagen chains with an abnormal mobility. Prolyl and lysyl hydroxylations were slightly increased. The abnormal molecules melted at a higher temperature than the normal ones. CNBr peptide mapping of type II collagen showed an altered electrophoretic migration of peptides CB 11, CB 8, and CB 10,5 whereas CB 9,7 looked normal. In addition, two small non-collagenous proteins isolated from cartilage were not found in an age-matched control individual but were detected in a normal newborn infant. The quantitation of proline-labelled collagen synthesized by dermal fibroblasts demonstrated a 50% reduction of total collagen. This decrease essentially affected the amount of extracellular type I collagen, which was secreted less efficiently than in control cells. Nevertheless, type I collagen chains behaved normally on 5% polyacrylamide gels. The reduced mRNA levels of alpha 1I and alpha 2I chains might reflect either a transcriptional defect or a decreased stability of mRNA transcripts. We suggest that the association of both pathological chondrocytes producing altered collagen type II and decreased synthesis of type I could be responsible for this peculiar phenotype. The overmodification of alpha 1II CNBr peptides is consistent with the presence of a single-base substitution in the COL2A1 gene. Whether there is a direct causal relationship between the type II collagen defect and the underexpression of type I collagen will require clarification.

[The advantages and limits of the use of desmopressin (Minirin) in stomatology. Apropos 2 young female patients presenting with von Willebrand's disease]. / Intérêts et limites de l'utilisation de la desmopressine (Minirin) en stomatologie. A propos de deux jeunes patientes présentant une maladie de Willebrand.

The authors describe two cases of wisdom tooth germ removal in female adolescents presenting with von Willebrand's disease. The effect of the Minirin injection was studied during a preoperative test and allowed carrying out the operation with normalized hemostasis, without using substitution factors and with no postoperative complications. The authors specify the indications and limitations of the use of desmopressin before surgery.

Pharmacokinetics of tiaprofenic acid in children after a single oral dose.

Twelve healthy children in three age groups anaesthetized for minor surgery were given a single oral dose of tiaprofenic acid (3 mg.kg-1) (TA). Seven blood samples and zero to 8 and 8 to 24 h urines were collected. TA concentrations in plasma and urine were measured by HPLC. No significant difference was found between the age groups in the kinetic parameters of TA and no correlation was found between these parameters and age: tmax = 2.12 h, Cmax = 8.78 mg.l-1, AUC(0----8 h) 33.9 mg.h.l-1, AUC = 39.3 mg.h.l-1, t1/2 = 2.35 h, Vt = 0.319 l.kg-1, CL = 0.094 l.h-1.kg-1. Renal clearance was 14 ml.h-1.kg-1.33% of the TA dose was recovered in the 24 h urine, 48% of which was conjugated, whereas in adults, TA is only found in urine as conjugates. The apparent plasma clearance was significantly higher (56%) than in 12 healthy adults given 1.5 mg.kg-1 TA. Volume of distribution and t1/2 did not significantly differ between children and adults. Since no relationship has been established between plasma TA and either efficacy or toxicity, a different dose regimen cannot be recommended in 3-11 year-old children from that in adults.

[Complete luxation of the upper incisor. Analysis of the mid-term results. Treatment of sequelae]. / Luxations totales d'incisives supérieures. Analyse des résultats à moyen terme. Traitement des séquelles.

The study involved 18 children aged 7 to 13 years, who all benefited from early reimplantation and appropriate immobilisation. Radicular treatment appeared to have little influence and adverse results, especially early rhizalysis, were common (50% versus 30% of good results). In the event of failure, dento-facial orthopedic treatment, where indicated, may provide a cosmetically acceptable solution.

[Ankyloblepharon filiforme adnatum and associated syndromes]. / L'ankyloblépharon filiforme congénital et les syndromes associés.

The authors present 2 cases of ankyloblepharon filiforme adnatum (AFA). In the first case, the ocular anomaly was unaccompagnied by other malformations; in the second patient, there was an associated popliteal pterygium syndrome. The authors review histologic, embryologic features and etiopathogenic theories of AFA and also fully discuss the various syndromes which may be associated with this ocular anomaly. Rosenman's classification is presented.

[Tooth and face abnormalities associated with pituitary growth hormone insufficiency]. / Les malformations dentaires et faciales associées à l'insuffisance hypophysaire en hormone de croissance.

Dental and facial examination has been performed in sixty-two children with idiopathic or congenital growth hormone deficiency. Fourteen (22%) had a malformation of the upper incisors and/or of the naso-frontal bud or of the eyes, associated in five with a malformation of the brain in the prosencephalon-derived areas. Moreover, fourteen patients had some facial abnormality in an area situated near that derived from the naso-frontal bud. These associations are to be considered as a clinical marker able to call for pituitary investigation in short children. They suggest that some cases of so-called idiopathic hypopituitarism relate in fact to congenital and malformative causes.

Ectopic secreting choroid plexus in the oropharynx.

The authors report a case of an ectopic secreting choroid plexus in the oropharyngeal region of a neonate. The lesion presented as a rapidly growing tumor, containing CSF. No communication with the cranial cavity could be found. Following two surgical interventions the lesion was entirely removed and pathological examination revealed choroid plexus.

[Untimely extraction in mandibular sarcoma. Apropos of 2 cases]. / L'extraction intempestive dans des sarcomes mandibulaires. A propos de deux cas.

Two patients with chondrosarcoma and fibrosarcoma of the mandible respectively were seen after abusive extraction of first molars from the tumoral regions. It is essential to recognize presenting signs of mandibular tumors since dental extractions are contraindicated in these cases. These untimely procedures increase the delay between the onset of the first clinical signs, the diagnosis, and the start of therapy, and thus make for a poorer prognosis.

[Lethal midline granuloma, An anatomoclinical study apropos of 3 cases]. / Le granulome malin centro-facial. Etude anatomo-clinique à propos de 3 observations.

In Midline malignant granuloma, a clinical entity characterized by necrotic ulcerations of the upper respiratory tract, two different histological features can be observed. The first one, called "idiopathic" granuloma, looks like simple granulation tissue and remains a strictly localized disease. In the second type (midline malignant reticulosis or histiocytosis), the granulation tissue contains atypical histiocytic cells. The 3 cases reported here belong to this last group. The early lesions were located in the nose (2 cases) or in the maxillary sinus (1 case). The histological analysis showed in all cases 20 to 40% of atypical histiocytes associated with other "inflammatory" cells. Radiotherapy was used in association with chemotherapy or surgery in the treatment. One patient is still alive at 3 years. We have no follow-up data for another patient. The third patient died after 18 months. An autopsy demonstrated multifocal visceral involvement by atypical histiocytes (malignant histiocytic lymphoma). The histogenesis of this disease, in light of histoenzymological and ultrastructural findings, and its possible relationship to lymphomatoid granulomatosis are discussed.