E. Arnaud

Quadruple distraction interne avec avancement fronto-facial précoce pour faciocraniosténose.

Introduction La strategie de prise en charge des faciocraniostenoses comprend habituellement au moins deux temps operatoires majeurs : un avancement frontal avant un an pour traiter la craniostenose, et un ou plusieurs avancements faciaux pour corriger la retrusion faciale. L’avancement fronto-facial monobloc (AFFM) est une intervention qui permet de corriger simultanement ces deux anomalies crânienne et faciale, mais, dans sa forme classique, sa morbidite en restreignait l’indication. Patients et methode Nous rapportons l’experience preliminaire de l’AFFM chez 20 enfants dont l’âge moyen etait de 3,2 ans (ages de 6 mois a 14 ans). L’intervention a consiste en une osteotomie de type fronto-faciale monobloc totale avec mobilisation peroperatoire sans avancement. Quatre distracteurs (Martin-Medizin), deux frontaux supra-orbitaires et deux faciaux temporo-malaires ont ete positionnes et syntheses avec du materiel d’osteosynthese resorbable ou metallique. Chez un des patients les plus jeunes, une broche transfaciale a ete utilisee entre les deux systemes malaires. La distraction a ete debutee a J7 en moyenne (J5 a J15) avec un rythme de 1 mm par jour sur chaque distracteur. L’avancement a ete mene jusqu’a la butee maximale des dispositifs ce qui a necessite de 15 a 20 jours. Le recul maximal a ete de 30 mois. Resultats La correction de l’exorbitisme superieur et inferieur a ete obtenue dans 18/19 cas permettant de retablir l’occlusion palpebrale dans les cas extremes. Chez un enfant pour lequel la course du distracteur a ete insuffisante (15 mm au lieu de 20), la correction a ete partielle. La correction de la retrusion maxillaire a egalement ete satisfaisante chez 17/19 cas. Deux episodes infectieux sont survenus durant cette phase initiale au niveau frontal et ont necessite le retrait d’un distracteur et l’arret de la distraction (2/19). Une rupture de l’un des distracteurs est survenue chez un des patients a egalement necessite une reintervention precoce. Un deces immediat par hypertension intracrânienne suraigue est survenu chez l’un des patients dans les 12 premieres heures avant meme que la distraction n’ait ete debutee, chez une maladie de Crouzon traitee tardivement. Chez trois des six premiers patients, l’ablation des dispositifs de distraction a 3-4 mois a eu pour consequence un recul secondaire. Pour les suivants, les dispositifs ont ete laisses plus de six mois et la conservation de l’avancement initial semblait obtenue, mais l’osteogenese restait limitee. Discussion L’utilisation de la distraction lors d’un avancement frontofacial monobloc semble en reduire la morbidite. Il serait ainsi possible d’augmenter les indications d’une telle procedure dont le principe est adapte aux faciocraniostenoses severes. L’insuffisance de croissance genetique necessite d’autres interventions ulterieurement. L’evolution a long terme reste a etre evaluee.

Clinical and neuroradiological features of the 9p deletion syndrome

BackgroundThe 9p deletion syndrome is a rare condition, which associates trigonocephaly, facial dysmorphism and developmental delay. The neuroradiological aspects of this syndrome have not yet been described. The purpose of this article is to identify the clinical and neuroradiological features, that should be recognized by all specialists treating these children, for a proper and early diagnosis.MethodsAmong patients with trigonocephaly treated at our institution, we retrospectively analyzed the clinical and neuroradiological aspects of children with genetically confirmed 9p deletion syndrome.Results6 patients were identified. Beside trigonocephaly, the most frequent clinical findings were small ears, long philtrum, upslanting palpebral fissures, flat nasal bridge and variable psycho-motor delay. Hypertelorism was present in 4 of 6 patient, which is opposite to the hypotelorism typical of non-syndromic trigonocephaly. Among neuroradiological findings, large, anteriorly rotated sylvian cisterns and altered shape of the septum pellucidum were found in all patients, as well as the compression of the frontal cortex due to the metopic synostosis (MS). A thin or dysmorphic corpus callosum and a diffuse white matter hypoplasia were present in more than half of the cases. Futhermore we compared these MRI findings with those of a control group of 30 non-syndromic trigonocephalies.ConclusionsSome recurrent neuroradiological alterations can be found in 9p deletion syndrome. The presence of these signs on MRI of a trigonocephalic patient should raise the suspicion of an underlying chromosomal alteration, such as the 9p deletion syndrome and prompt genetic investigations.

Diagnostic d'une asymétrie faciale et crânio-faciale

Craniofacial asymmetry is caused by various aetiologies but clinical examination remains the most important criteria since minor asymmetry is always present. The diagnosis can be confirmed by anthropometric measurements and radiological examinations but only severe asymmetries or asymmetries with an associated functional impairment should be treated. The treatment depends on the cause, and on the time of appearance. Congenital asymmetries might be treated early, during the first year of life if a craniosynostosis is present. Hemifacial microsomia are treated later if there is no breathing impairment. Since the pediatricians have recommended the dorsal position for infant sleeping, an increasing number of posterior flattening of the skull has been appearing, and could be prevented by adequate nursing. Other causes of craniofacial asymmetries are rare and should be adapted to the cause (tumors, atrophies, neurological paralysis, hypertrophies) by a specialized multidisciplinar team.

Crouzon syndrome and Bent bone dysplasia associated with mutations at the same Tyr‐381 residue in FGFR2 gene

To the Editor : We report the identification of novel p.Tyr381Asn (c.1141T>A) mutation in FGFR2 gene in a family affected by Crouzon syndrome (MIM:123500). This mutation is located at the same residue than the mutation (p.Tyr381Asp, c.1141T>G) recently described in the perinatal lethal Bent bone dysplasia (BBD) (1). Crouzon syndrome was suspected in the proband at the age of 3 years. Birth parameters were weight: 2940 g, length: 46 cm, and head circumference: 37 cm. At the age of 3 years, he presented with a scaphocephaly with bilateral exophthalmos, parrot-beaked nose and frontal bossing (Fig. 1). A pronounced nasal obstruction with septal deviation and a malocclusion was observed. A skull computed tomography (CT) examination

FGFR2 splice site mutations in Crouzon and Pfeiffer syndromes: two novel variants

To the Editor: Fibroblast growth factor receptor 2 (FGFR2) is a key-gene involved in syndromic craniosynostoses, such as Crouzon and Pfeiffer syndromes. Patients usually carry missense mutations, affecting exons 8 (IIIa) and 10 (IIIc), but rare splicing sites mutations have been described, in the intronic regions flanking exon IIIc, or in exon IIIc itself (1). No clear genotype–phenotype correlation has been identified yet for this group of variants. We clinically analyzed a series of patients diagnosed with syndromic craniosynostosis, to identify phenotypical characteristics for patients with splicing sites mutations. Among the 160 patients diagnosed with Crouzon or Pfeiffer syndrome at Necker-Enfants Malades since 2008, 8 (5% IC95 1.6–8.4%) have pathogenic variants affecting splicing, located in 6 different sites (cf Table 1). We report two novel variants, c.940-10T>A and c.994_1041del. The prediction softwares (MaxEnt, NNSPLICE, GeneSplicer, and ESEfinder) show that all of them can modify exon IIIc splicing, via modification of acceptor/donor sites, or fixation of different trans-regulators exon splicing enhancer proteins (cf Table S1, Supporting information). Splicing alterations can modify the probability of activating one splice site preferentially to another, leading to a new repartition of FGFR2 transcripts and eventually modifying the expression of the receptor in the different tissues. This could explain the large spectrum of phenotypes observed in syndromic craniosynostoses, from mild Crouzon to very severe Pfeiffer syndromes. Several mechanisms have been described: disruption of the utilization of exon IIIc, leading to ectopic expression of keratinocyte growth factor receptor in fibroblasts (c.940-2A>T) (2), creation of a new cryptic splice site resulting in an altered receptor (c.1032 G>A) (3, 4), loss of a donor site, prompting the use of the cryptic site, thus activating the FGFR2 receptor and leading to premature suture fusion (c.1084+3A>G) (3, 5). Phenotypes of our eight patients with splice site mutations (cf Fig. 1; Table S2) can be divided into three groups. Group 1: cases 1 (c.940-10 T>A) and 8 (c.1084+3 A>G) have a classical Crouzon syndrome with coronal fusion and typical facial appearance with exorbitism and midface retrusion. Case 1 was diagnosed with papilledema and elevated intracranial pressure. Case 8 had laparoschisis at birth. They both needed craniofacial surgery. Group 2: cases 4 (c.994_1041 del), Table 1. Fibroblast growth factor receptor 2 splice site variants identified in patients with Crouzon or Pfeiffer syndrome screened at Necker-Enfants Malades craniofacial Unit, and review of already published cases

L’innovation en chirurgie craniofaciale : depuis Tessier jusqu’aux perspectives futures. D’après les témoignages de F. Ortiz-Monasterio, D. Marchac, F. Firmin et T. Wolfe

Innovation is one of the founding values of plastic surgery. By its fundamental innovations, Paul Tessier (1917-2008) created craniofacial surgery in the sixties. The exploration of the new field, which has modified the boundaries of knowledge, has been evoked by Fernando Ortiz Monasterio, Daniel Marchac, Françoise Firmin and Tony Wolfe. This work defined the human qualities leading to creative breakthrough: (1) rigourous work and passion; (2) withdrawal from the current educative dogmas; (3) maintainance of the excellence of reconstructive and aesthetic practice; (4) progressive complexity of the procedures with concomitant validation by peers; (5) humility and continuous self criticizing maintained in ones own results. The main focus of those evolutions in craniofacial care at the forefront include among others: (1) functional imaging in order to help for mental prognosis assessment; (2) sophistication of biomaterials in order to limit morbidity; (3) ultimate developments of osteogenic distraction techniques; (4) genetic evaluation and counselling toward genetic therapies; (5) antenatal diagnosis toward in utero treatment. The necessity of well recognized reference centers for treatment of craniofacial anomalies is currently one of the healthcare priorities in Europe among the management of all are rare diseases (less than one out of 2000 living births).