Marie-Paule Vazquez

Arteriovenous malformations of the dental arcades the place of endovascular therapy: results in 12 cases are presented

Twelve arteriovenous malformations of the dental arcades (AVMDAs) (seven mandibular and five maxillary) were seen in our institution between 1977 and 1997. All these lesions consisted of true arteriovenous shunts (of either nidus or fistulous type) involving the bone, with or without soft tissue extension. Haemorrhage was present in eight patients (67%); either torrential, necessitating emergency embolization, or recurrent and progressive. Teeth instability was detected in all patients and was the origin of the bleeding. All lesions were embolized. Lesions in nine patients were embolized with Polyvinyl Alcohol Particles (PVA): this helped to stabilize the situation but could not avoid recurrences in all patients, necessitating complementary embolizations and or surgery. The use of acrylic glue (N-Butyl-Cyano-Acrylate [NBCA] Histoacryl) as the embolic agent has changed the results obtained tremendously. Eight patients have been treated with NBCA (five as complementary therapy to PVA during later sessions and three at the first attempt); injection either via the transarterial route or direct transcutaneous puncture (four patients) achieved a cure in four of these lesions (34%) with stability at long-term follow-up of all the other AVMs. Embolization with glue represents the therapy of choice in these sometimes life-threatening lesions, achieving a cure if directed towards the osseous venous lakes. Surgery, often leading to facial mutilation and necessitating massive reconstruction should be avoided nowadays, at least as the initial therapy.

Mutations in SNRPB, Encoding Components of the Core Splicing Machinery, Cause Cerebro-Costo-Mandibular Syndrome

Cerebro‐costo‐mandibular syndrome (CCMS) is a developmental disorder characterized by the association of Pierre Robin sequence and posterior rib defects. Exome sequencing and Sanger sequencing in five unrelated CCMS patients revealed five heterozygous variants in the small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) gene. This gene includes three transcripts, namely transcripts 1 and 2, encoding components of the core spliceosomal machinery (SmB′ and SmB) and transcript 3 undergoing nonsense‐mediated mRNA decay. All variants were located in the premature termination codon (PTC)‐introducing alternative exon of transcript 3. Quantitative RT‐PCR analysis revealed a significant increase in transcript 3 levels in leukocytes of CCMS individuals compared to controls. We conclude that CCMS is due to heterozygous mutations in SNRPB, enhancing inclusion of a SNRPB PTC‐introducing alternative exon, and show that this developmental disease is caused by defects in the splicing machinery. Our finding confirms the report of SNRPB mutations in CCMS patients by Lynch et al. (2014) and further extends the clinical and molecular observations.

Functional Assessment of Disease-Associated Regulatory Variants In Vivo Using a Versatile Dual Colour Transgenesis Strategy in Zebrafish

Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function.

Prune belly syndrome: modified Monfort abdominoplasty with a horizontal scar and a dermal layer

Prune belly syndrome is a rare congenital disease occurring in 1/40,000 births, mostly in male patients. Abdominal hypoplasia has aesthetic and functional consequences on breathing, intestinal transit, and stature. Thus, the goal of the surgical treatment must be both functional and aesthetic. Through two cases, we present a modified technique of the usual abdominoplasty to obtain better functional and aesthetic results. Two male patients have been operated on, when they, respectively, were 10xa0months old and 3xa0years old. Our surgical technique was inspired from Callia’s as we used a horizontal incision, and from the Monfort abdominoplasty for the muscular wall repair, which we reinforced by preserving a dermal layer under the umbilicus. Patients have been followed up 1 to 2xa0years. We reported a functional and aesthetic improvement in both patients, and no complication occurred. These preliminary results showed satisfactory functional and aesthetic results with a hidden scar.Level of Evidence: Level V, therapeutic study.

Tumeurs kératokystiques odontogènes de l’enfant et syndrome de Gorlin. Comment expliquer les récidives et l’agressivité des lésions ?

INTRODUCTIONnKeratocystic odontogenic tumors (KOT), as complications in Nevoid Basal Cell Carcinoma Syndrome (NBCCS), occur early (before 20 years of age) and are usually more aggressive. The aim of this retrospective study was to determine the clinical, histological, and genetic phenotype, of these lesions and to define predictive features of aggressiveness.nnnPATIENTS AND METHODSnWe retrospectively studied five patients presenting with one or several KOT with NBCCS. We collected their clinical, radiological, and therapeutic data, rate of recurrence or new localization. Anatomopathological examinations were reviewed systematically. Somatic PTCH, SMO and SMAD 4 sequencing were completed.nnnRESULTSnThe average age at diagnosis was 11.2 years. The average number of KOT was 3.2 most often located in the molar region. All the cysts were enucleated. Anatomopathological examination revealed the presence of satellite cysts and daughter cysts and epithelial expansion in more than 80% of cases. No somatic mutation was observed among KOT.nnnDISCUSSIONnKOT develop in the first 10 years, in patients presenting with NBCCS, and recurrence is observed in the second and third decade. KOT are typically aggressive and have a tendency to recur, especially in patients with NBCCS. Anatomopathological examination may be predictive of the lesions aggressiveness. Understanding the genetic and immunological mechanisms should open the way for new medical treatment.

PTCH1 mutation and local aggressiveness of odontogenic keratocystic tumors in children: is there a relationship?

Keratocystic odontogenic tumors (KCOTs) are locally aggressive jaw lesions that may be related to PTCH1 mutations in isolation or in association with nevoid basal cell carcinoma syndrome. We sought to clarify the role of PTCH1 mutation in KCOT aggressiveness. We assessed cyst pathological characteristics, Ki-67 immunostaining, and somatic and germinal PTCH1 mutation in 16 KCOTs from 10 unrelated patients. Ten PTCH1 mutations were identified in 16 tumors. All tumors with PTCH1 mutations presented the criteria of pathological aggressiveness. We also noted the presence of a chorionic epithelial structure apparently acting as a secondary germinal center in these same tumors. Ki-67 immunostaining was not associated with PTCH1 mutation. KCOTs harboring the mutation display a chorionic epithelial structure that acts as a secondary germinal center. Genetic and microenvironmental factors might interact to propel tumor development.

Article originalTumeurs kératokystiques odontogènes de l’enfant et syndrome de Gorlin. Comment expliquer les récidives et l’agressivité des lésions ?Pediatric keratocystic odontogenic tumor and nevoid basal cell carcinoma syndrome. Predictive factors for recurrence and aggressiveness

INTRODUCTIONnKeratocystic odontogenic tumors (KOT), as complications in Nevoid Basal Cell Carcinoma Syndrome (NBCCS), occur early (before 20 years of age) and are usually more aggressive. The aim of this retrospective study was to determine the clinical, histological, and genetic phenotype, of these lesions and to define predictive features of aggressiveness.nnnPATIENTS AND METHODSnWe retrospectively studied five patients presenting with one or several KOT with NBCCS. We collected their clinical, radiological, and therapeutic data, rate of recurrence or new localization. Anatomopathological examinations were reviewed systematically. Somatic PTCH, SMO and SMAD 4 sequencing were completed.nnnRESULTSnThe average age at diagnosis was 11.2 years. The average number of KOT was 3.2 most often located in the molar region. All the cysts were enucleated. Anatomopathological examination revealed the presence of satellite cysts and daughter cysts and epithelial expansion in more than 80% of cases. No somatic mutation was observed among KOT.nnnDISCUSSIONnKOT develop in the first 10 years, in patients presenting with NBCCS, and recurrence is observed in the second and third decade. KOT are typically aggressive and have a tendency to recur, especially in patients with NBCCS. Anatomopathological examination may be predictive of the lesions aggressiveness. Understanding the genetic and immunological mechanisms should open the way for new medical treatment.

Predictors of speech outcomes in children with Pierre Robin sequence

BACKGOUNDnPierre Robin sequence (PRS) has worse speech outcomes than isolated cleft palate. We aimed to search for possible associations of phonological outcomes with PRS status (isolated vs syndromic), clinical severity, soft palate muscles deficiency, or surgical procedure.nnnMETHODSnWe designed a retrospective study of 130 children (male/female ratio: 0.4) with isolated (96) or syndromic (34) PRS with cleft palate. Grading systems were used to classify retrognathia, glossoptosis, and respiratory and feeding disorders. Electromyography was used to investigate levator veli palatini muscles. Hard cleft palate was measured using maxillary casts. Intravelar veloplasty was performed usingxa0the Sommerlads technique. Phonological outcomes were assessed using the Borel-Maisonny classification.nnnRESULTSnCleft palate was repaired in one stage (65.5%) or hard palate closure was postponed (34.5%). Velopharyngeal insufficiency was more frequent in syndromic PRS (53%) vs. isolated PRS (30.5%) (pxa0=xa00.01), but was not statistically associated with clinical grade, hard cleft palate width, soft palate electromyography, and surgical procedure.nnnCONCLUSIONSnIn children with PRS, anatomic variables, initial clinical severity, and soft palate muscle deficiency are not predictors of speech prognosis.

Microsomies hémifaciales et distraction mandibulaire intra-orale. Vers des indications précises

Resume Les hypoplasies mandibulaires dans le cadre des microsomies hemifaciales ont largement beneficie des techniques de distraction, en particulier intra-orale. Ces techniques sont en effet realisables chez lenfant, le replacant dans une meilleure configuration morphologique, psychologique et fonctionnelle. Elles peuvent redynamiser la croissance et en tout cas diminuer les deformations secondaires a lhypoplasie mandibulaire. Les auteurs, a partir de criteres precis, proposent une classification chirurgicale pour faciliter la prise de decision therapeutique. La distraction intra-orale, parfois bidirectionnelle, dont les resultats sont equivalents a la distraction externe, presente de nombreux avantages qui, dans la grande majorite des cas, la font preferer maintenant a la distraction externe. Son action tridimensionnelle (3D) sur los et les parties molles et le suivi a long terme se doivent detre evalues plus objectivement comme peuvent le permettre les comparaisons pre- et post-distraction stereolithographiques ou photogrammetriques en 3D. Elle doit etre consideree chez lenfant comme le premier temps de chirurgie squelettique preparant a un eventuel deuxieme temps dorthopedie, dorthodontie ou de chirurgie orthognathique facilitee apres la puberte. Chez ladulte jeune, elle est en concurrence avec la chirurgie conventionnelle, mais laspect progressif, lent, respectueux des articulations temporo-mandibulaires permet dans les asymetries mandibulaires une adaptation permettant deviter le recours a losteotomie controlaterale ou a une greffe osseuse.

Injuries to the Face, Neck, Mouth, and Scalp

The head and neck are exposed and vulnerable to physical abuse. This chapter focuses exclusively on injuries to the face, neck, mouth, and scalp; intracranial injuries are discussed in another chapter. The face is the most frequently injured part of the body. While face and scalp injuries are readily accessible to diagnosis, they can be minor, healing, or, frequently, trivialized by practitioners. Intraoral and dental trauma often go unrecognized and should always be looked for. Anything that seems suspicious—multiple lesions at different stages of healing, lesions in uncommon locations for accidental injury, a failure to seek treatment for such lesions, a lack of concordance with the reported history—should alert the clinician to the possibility of abuse. Due to their location, facial sequelae and scarring are always visible and can impact a child’s inclusion both in society and at school.