PCR array analysis identified hyperproliferation but not autophagy or apoptosis in fibrous epulis.

BACKGROUND: The pathogenesis of fibrous epulis is still quite unclear. Our recent genome-wide RNA sequencing analysis revealed that in fibrous epulis, RAS-PI3K-AKT-NF-κB pathway regulates the expression of Bcl-2 family and IAP family genes, leading to increased proliferation and the inhibition of apoptosis. The PI3K/AKT signaling pathway can promote autophagy in human gingival fibroblasts; therefore, the purpose of the present study was to identify whether autophagy is involved in the pathogenesis of fibrous epulis. METHODS: Differentially expressed genes (DEGs) between fibrous epulis lesions and normal gingival tissues were identified using the PCR array. The expression levels of eighteen autophagy-related (ATG) family genes, twelve B-cell lymphoma 2 (Bcl-2) family genes, and eleven cysteine-dependent aspartate-directed protease (caspase) family genes were validated using quantitative real-time PCR (qRT-PCR). Autophagy induction was determined by measuring microtubule-associated protein light chain 3 (LC3) conversion (LC3-I to LC3-II) by immunoblot analysis. RESULTS: The PCR array identified six upregulated genes, whereas no genes were expressed at significantly lower levels. The upregulated genes were BCL2, BCL2L1, CXCR4, HSP90AA1, HSPA8, and IGF1, which all belong to the "regulation of autophagy" group but not the "autophagy machinery components" group. qRT-PCR verified that the expression levels of BCL2, BCL2L1 (also known as BCL-XL), and BCL2L2 (also known as BCL-W) were significantly increased in fibrous epulis. No LC3-I to LC3-II conversion was observed. CONCLUSIONS: The present study reveals that in fibrous epulis, Bcl-2 and Bcl-xL coordinately mediate gingival cell escape from apoptosis, leading to uncontrolled proliferation. Moreover, ATG family genes are not activated, and autophagy is not involved in this process.

EXOME REPORT: Novel mutation in ATP6V1B2 segregating with autosomal dominant epilepsy, intellectual disability and mild gingival and nail abnormalities.

Mutations in ATP6V1B2, which encodes the B2 subunit of the vacuolar H + ATPase have previously been associated with Zimmermann-Laband syndrome 2 (ZLS2) and deafness-onychodystrophy (DDOD) syndrome. Recently epilepsy has also been described as a potentially associated phenotype. Here we further uncover the role of ATP61VB2 in epilepsy and report autosomal dominant inheritance of a novel missense variant in ATP6V1B2 in a large Polish family with relatively mild gingival and nail problems, no phalangeal hypoplasia and with generalized epilepsy. In light of our findings and review of the literature, we propose that the ATP6V1B2 gene should be considered in families with autosomal dominant epilepsy both with or without intellectual disability, and that presence of subtle gingival and nail problems may be another characteristic calling card of affected individuals with ATP6V1B2 mutations.

The RAS-PI3K-AKT-NF-κB pathway transcriptionally regulates the expression of BCL2 family and IAP family genes and inhibits apoptosis in fibrous epulis.

BACKGROUND: Epulis has a tumor-like appearance but is considered to be a massive reactive lesion rather than a true neoplasia. Limited information about the pathogenesis of epulis is available. The purpose of our study was to identify potential signaling pathways in fibrous epulis through transcriptome profiling. METHODS: Differentially expressed genes (DEGs) between fibrous epulis lesions and normal gingival tissues were detected using RNA sequencing (RNAseq). The expression levels of eighteen genes were validated using quantitative real-time PCR (qRT-PCR). RESULTS: RNAseq identified 533 upregulated genes and 732 downregulated genes. The top 10 upregulated genes were IL11, OSM, MMP3, KRT75, MMP1, IL6, IL1B, IL24, SP7, and ADGRG3. The top 10 downregulated genes were BCHE, TYR, DCT, KRT222, RP11-507K12.1, COL6A5, PMP2, GFRA1, SCN7A, and CDH19. KEGG pathway analysis further indicated that the DEGs were enriched in "Pathways in cancer" and the "Ras signaling pathway". quantitative real-time PCR verified that the expression levels of SOS1, HRAS, PIK3CA, AKT3, IKBKA, IKBKB, NFKB1, BCL2, BCL2L1, XIAP, BIRC2, and BIRC3 were increased significantly. CONCLUSIONS: The current transcriptomic profiling study reveals that in fibrous epulis, RAS-PI3K-AKT-NF-κB pathway transcriptionally regulates the expression of BCL2 family and IAP family genes, leading to increased proliferation and apoptosis inhibition.

Establishment and genomic characterization of gingivobuccal carcinoma cell lines with smokeless tobacco associated genetic alterations and oncogenic PIK3CA mutation.

Smokeless tobacco associated Gingivobuccal squamous cell carcinoma (GB-SCC) is a major public health problem but available oral cancer cell lines are mostly from smoking associated tongue SCC raising the need for pertinent GB-SCC cell line models. As part of the International Cancer Genome Consortium (ICGC) Project, 4 novel cell lines, namely, Indian Tata Memorial Centre Oral Cancer (ITOC) -01 to -04 were established and characterized with conventional methods, karyotyping, ultrastructure, in vivo tumourigenicity, Whole exome sequencing (WES) and RNA sequencing. These hyperploid cell lines form xenografts in mice and show metabolically active and necrotic areas on fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging. WES of ITOC cell lines recapitulate the genomic tumor profile of ICGC GB-SCC database. We further identified smokeless tobacco associated genetic alterations (PCLO, FAT3 and SYNE2) and oncogenic PIK3CA mutation in GB-SCC cell lines. Transcriptome profiling identified deregulation of pathways commonly altered in cancer and down-regulation of arachidonic acid metabolism pathway, implying its possible role in GB-SCC. Clinical application of high throughput sequencing data depends on relevant cell line models to validate potential targets. Extensively characterized, these oral SCC cell lines are particularly suited for mechanistic studies and pre-clinical drug development for smokeless tobacco associated oral cancer.

Prevalence of p53 dysregulations in feline oral squamous cell carcinoma and non-neoplastic oral mucosa.

Squamous cell carcinoma is the most common malignant oral tumor in cats. The late presentation is one of the factors contributing to the detrimental prognosis of this disease. The immunohistochemical expression of the p53 tumor suppressor protein has been reported in 24% to 65% of feline oral squamous cell carcinomas, but no study has systematically evaluated in this tumor the presence of p53 encoding gene (TP53) mutations. The aim of this retrospective study was to determine whether p53 immunohistochemistry accurately reflects the mutational status of the TP53 gene in feline oral squamous cell carcinoma. Additionally, the prevalence of p53 dysregulation in feline oral squamous cell carcinoma was compared with that of feline non-neoplastic oral mucosa, in order to investigate the relevance of these dysregulations in cancer development. The association between p53 dysregulations and exposure to environmental tobacco smoke and tumor characteristics was further assessed. Twenty-six incisional biopsies of oral squamous cell carcinomas and 10 cases each of lingual eosinophilic granuloma, chronic gingivostomatitis and normal oral mucosa were included in the study. Eighteen squamous cell carcinomas (69%) expressed p53 and 18 had mutations in exons 5-8 of TP53. The agreement between immunohistochemistry and mutation analysis was 77%. None of non-neoplastic oral mucosa samples had a positive immunohistochemical staining, while one case each of eosinophilic granuloma and chronic gingivostomatitis harbored TP53 mutations. Unlike previously hypothesized, p53 dysregulations were not associated with exposure to environmental tobacco smoke. These results suggest an important role of p53 in feline oral tumorigenesis. Additionally, the immunohistochemical detection of p53 expression appears to reflect the presence of TP53 mutations in the majority of cases. It remains to be determined if the screening for p53 dysregulations, alone or in association with other markers, can eventually contribute to the early detection of this devastating disease.

Allele-specific polymerase chain reaction for the detection of single nucleotide polymorphism in amlodipine-induced gingival enlargement.

WHAT IS KNOWN AND OBJECTIVE: Studies indicate that there is an increased serum concentration of amlodipine (a calcium channel blocker used to treat hypertension and angina) in patients having mutant multidrug resistance 1 (MDR1) gene. Hence, genetic factors may play a very significant role in amlodipine-induced complications including gingival enlargement. CASE DESCRIPTION: Three patients with amlodipine-induced gingival enlargement showed improvement following drug substitution of amlodipine with enalapril (an angiotensin-converting enzyme inhibitor) and non-invasive periodontal therapy. Using allele-specific polymerase chain reaction, single nucleotide polymorphism of MDR1 gene of heterozygous mutant type (CT genotype) was identified in all three cases. WHAT IS NEW AND CONCLUSION: Drug-induced complications can potentially be a result of genetic factors, in combination with various local and systemic factors. Identifying genetic polymorphisms early might help predict adverse reactions and determine prognosis.

Regulatory roles of microRNAs in human dental tissues.

MicroRNAs (miRNAs) are a class of small, non-coding RNAs that provide an efficient pathway for regulation of gene expression at a post-transcriptional level. Tooth development is regulated by a complex network of cell-cell signaling during all steps of organogenesis. Most of the congenital dental defects in humans are caused by mutations in genes involved in developmental regulatory networks. Whereas the developmental morphological stages of the tooth development already are thoroughly documented, the implicated genetic network is still under investigation. The involvement of miRNAs in the regulation of tooth genetic network was suggested for the first time in 2008. MiRNAs regulate tooth morphogenesis by fine-tuning the signaling networks. Unique groups of miRNAs are expressed in dental epithelium compared with mesenchyme, as well as in molars compared with incisors. The present review focuses on the current state of knowledge on the expression and function of miRNAs in human dental tissues, including teeth and the surrounding structures. Herein, we show that miRNAs exhibit specific roles in human dental tissues and are involved in gingival and periodontal disease, tooth movement and eruption, dental pulp physiology including repair and regeneration, differentiation of dental cells, and enamel mineralization. In light of similarities between the tooth development and other organs originating from the epithelium, further understanding of miRNAs` function in dental tissues may have wide biological relevance.

Genomic analysis of gum disease and hypertrichosis in foxes.

Since the 1940s, a proliferative gingival disease called hereditary hyperplastic gingivitis (HHG) has been described in the farmed silver fox, Vulpes vulpes (Dyrendahl and Henricson 1960). HHG displays an autosomal recessive transmission and has a pleiotropic relationship with superior fur quality in terms of length and thickness of guard hairs. An analogous human disease, hereditary gingival fibromatosis (HGF), is characterized by a predominantly autosomal dominant transmission and a complex etiology, occurring either as an isolated condition or as a part of a syndrome. Similar to HHG, the symptom most commonly associated with syndromic HGF is hypertrichosis. Here we explore potential mechanisms involved in HHG by comparison to known genetic information about hypertrichosis co-occurring with HGF, using an Affymetrix canine genome microarray platform, quantitative PCR, and candidate gene sequencing. We conclude that the mitogen-activated protein kinase pathway is involved in HHG, however despite involvement of the mitogen-activated protein kinase kinase 6 gene in congenital hypertrichosis with gingival fibromatosis in humans, this gene did not contain any fixed mutations in exons or exon-intron boundaries in HHG-affected foxes, suggesting that it is not causative of HHG in the farmed silver fox population. Differential up-regulation of MAP2K6 gene in HHG-affected foxes does implicate this gene in the HHG phenotype.

A missense mutation accelerating the gating of the lysosomal Cl-/H+-exchanger ClC-7/Ostm1 causes osteopetrosis with gingival hamartomas in cattle.

Chloride-proton exchange by the lysosomal anion transporter ClC-7/Ostm1 is of pivotal importance for the physiology of lysosomes and bone resorption. Mice lacking either ClC-7 or Ostm1 develop a lysosomal storage disease and mutations in either protein have been found to underlie osteopetrosis in mice and humans. Some human disease-causing CLCN7 mutations accelerate the usually slow voltage-dependent gating of ClC-7/Ostm1. However, it has remained unclear whether the fastened kinetics is indeed causative for the disease. Here we identified and characterized a new deleterious ClC-7 mutation in Belgian Blue cattle with a severe symptomatology including perinatal lethality and in most cases gingival hamartomas. By autozygosity mapping and genome-wide sequencing we found a handful of candidate variants, including a cluster of three private SNPs causing the substitution of a conserved tyrosine in the CBS2 domain of ClC-7 by glutamine. The case for ClC-7 was strengthened by subsequent examination of affected calves that revealed severe osteopetrosis. The Y750Q mutation largely preserved the lysosomal localization and assembly of ClC-7/Ostm1, but drastically accelerated its activation by membrane depolarization. These data provide first evidence that accelerated ClC-7/Ostm1 gating per se is deleterious, highlighting a physiological importance of the slow voltage-activation of ClC-7/Ostm1 in lysosomal function and bone resorption.

Retrospective investigation of gingival invaginations: Part II: microbiological findings and genetic risk profile.

BACKGROUND AND OBJECTIVE: Gingival invaginations are a frequent finding during tooth extraction and following orthodontic space closure. Based on the interdental localization and sometimes pronounced depth, it has been suggested that a gingival invagination may impede oral hygiene. In Part I of this series, the time until active tooth movement and the localization of extraction were identified as potential risk factors for the development of gingival invagination. The aims of the present study were the analysis of the microbial spectrum of a gingival invagination in comparison with pool samples of the sulcus of Ramfjord teeth, on the one hand, and the importance of genetic variations of the pro-inflammatory mediator interleukin-1 (IL-1) and its receptor antagonist (IL-1-RN), on the other hand. In addition, a possible role of smoking as a risk factor was evaluated. SUBJECTS AND METHODS: A total of 30 patients with (n=16) and without (n=14) gingival invagination were examined for the presence of eleven periodontal pathogen bacterial species with a commercially available test (micro-IDent®Plus, Hain Lifescience, Nehren, Germany). The genetic evaluation was performed with the GenoType® IL-1 test (Hain Lifescience). RESULTS: The results of the microbiological analysis of gingival invaginations showed that the bacterial flora might differ or even be higher than the pool sample from sulcus regions. The genetic evaluation demonstrated that in the group without gingival invagination only 14% showed an IL-1 polymorphism, whereas this value was twice as high (35%) in the group with gingival invagination. In addition, a combination of both polymorphisms IL-1 and IL-1-RN was only found in patients with gingival invagination (25%). Interestingly, smoking patients showed a significant increase of the severity of the gingival invagination. CONCLUSION: This retrospective study demonstrated that gingival invagination might be accompanied with an altered microbiological bacterial spectrum and a genetic IL-1 polymorphism. In addition, smoking was identified as another potential risk factor for the severity of gingival invaginations.

Periodontal conditions in Williams Beuren syndrome: a series of 8 cases.

BACKGROUND: Williams Beuren syndrome (WBS) is an unusual hereditary connective tissue disease caused by a microdeletion at position 7q11-23 and a haploinsufficiency at the elastin gene. The most frequent specific features are elf-like face, alteration of cognitive functions and cardiovascular diseases including isolated supravalvular aortic stenosis. A number of clinical findings have been reported, but none of the studies evaluating this syndrome consider the oral cavity. It is equally surprising that the gingival tissue, which carries a perfectly structured elastic fibre network, has not yet been investigated. It is important to verify whether subjects affected by WBS are more susceptible to periodontal disease than healthy subjects who are not that much affected, for periodontal disease may have deleterious effects on the cardiovascular system. METHODS: In an attempt to address this issue, the oral manifestations of 8 patients (ages from 5 to 12 years) with WBS have been investigated: dental examination, periodontal examination (gingival phenotype, plaque control record, gingival index, bone quality). RESULTS: All patients had oral parafunction, tooth number abnormalities and malocclusions. Average gingival height and width were greater than normal. Plaque index was always very high except for one patient, but the gingival inflammation was not linked to the quantity of clinical plaque index. There was no obvious loss of attachment. CONCLUSION: As with collagen, elastin is a structural macromolecule of the gingiva. These components play an important role in gingival function and in the resistance of the periodontium to daily aggressions. Unlike genetic diseases characterized by impairment of collagen macrofibrils, it is suggested that the hemizygous gene encoding elastin does not result in periodontal disease. In addition there is an existence of a possible concordance between the elastin gene haploinsufficiency and the periodontal phenotype. There might be some adaptive process to this deficiency.

Focal epithelial hyperplasia (Heck's disease): report of a case in a girl of Brazilian Indian descent.

Summary. Background. This report describes the case of a patient with focal epithelial hyperplasia (FEH), a rare but distinctive entity of viral aetiology with characteristic clinical and histopathological features. Case report. The condition is usually seen in children and adolescents of American Indian and Eskimo background. Surgical removal of papillomatous lesions is the treatment of choice, either for aesthetic reasons, or when the lesions interfere with function or are readily traumatized. Recurrence and the site of new lesions are unpredictable, and continued review of the patient is often necessary. The patient described here has been followed for 24 months without recurrences or changes in the aspect of the remaining lesions. Conclusion. This case highlights a possible genetic predilection for FEH, since the patient is a descent of a Brazilian Xavante Indian.

Las enfermedades periodontales como infecciones bacterianas / Periodontal diseases as bacterial infection

Las infecciones periodontales son un conjunto de enfermedades localizadas en las encías y estructuras de soporte del diente. Están producidas por ciertas bacterias provenientes de la placa bacteriana. Estas bacterias son esenciales para el inicio de la enfermedad, pero existen factores predisponentes del hospedador y microbianos que influyen en la patogénesis de la enfermedad. La microbiota bacteriana periodontopatógena es necesaria pero no suficiente para que exista enfermedad, siendo necesaria la presencia de un hospedador susceptible. Estas enfermedades se han clasificado en gingivitis, limitadas a las encías y periodontitis, extendidas a tejidos más profundos. La clasificación de las enfermedades periodontales ha ido variando a lo largo de los años y es en el International Workshop for a Clasification of Periodontal Diseases and Conditions, en 1999, cuando se aprueba la clasificación que se expone en este trabajo. En él, se hace una revisión global de los diferentes cuadros de las enfermedades periodontales. Posteriormente, se propone el empleo de antibioterapia de utilización sistémica como la amoxicilina, amoxicilina-clavulánico y metronidazol como primera opción de tratamiento coadyuvante de estas enfermedades (AU)

The periodontal disease is conformed by a group of illnesses affecting the gums and dental support structures. They are caused by certain bacteria found in the bacterial plaque. These bacteria are essential to the onset of illness; however, there are predisposing factors in both the host and the microorganisms that will have an effect on the pathogenesis of the illness. Periodontopathogenic bacterial microbiota is needed, but by itself, it is not enough to cause the illness, requiring the presence of a susceptible host. These diseases have been classified as gingivitis, when limited to the gums, and periodontitis, when they spread to deeper tissues. Classification of periodontal disease has varied over the years.The one used in this work was approved at the International Workshop for a Classification of Periodontal Diseases and Conditions, held in 1999. This study is an overview of the different periodontal disease syndromes. Later, the systematic use of antibiotic treatment consisting of amoxicillin, amoxicillinclavulanic acid, and metronidazole as first line coadjuvant treatment of these illnesses will be reviewed (AU)

Focal palmoplantar and gingival keratosis: a distinct palmoplantar ectodermal dysplasia with epidermolytic alterations but lack of mutations in known keratins.

Focal palmoplantar and gingival keratosis is a rare autosomal dominant disease whose clinical features, and in particular, pathologic alterations and molecular etiology remain to be well defined. Recently we observed a German family affected by the disease in at least 3 consecutive generations. The 4 patients examined showed circumscribed and painful hyperkeratosis at the weight-bearing plantar skin since infancy, rather mild palmar hyperkeratosis, and continuous leukokeratosis confined to the maxillary and mandibulary attached gingiva. There were no nail changes, subungeal keratoses, or follicular hyperkeratosis. Light and electron microscopy of the plantar and gingival lesions revealed alterations of epidermolytic hyperkeratosis. Mutations in the known keratin genes were excluded by linkage analysis using microsatellite markers. We conclude that focal palmoplantar and gingival keratosis is a clinically distinct palmoplantar ectodermal dysplasia that is pathologically characterized by epidermolytic alterations, but is most probably not caused by a mutation in a keratin gene.

Enfermedad periodontal: una nueva clasificación / Periodontal disease: a new classification

La enfermedad periodontal sigue siendo una de las patologías de mayor incidencia en la población en general, además de ser una de las causantes de pérdida de dientes, se considera como un factor de riesgo para ciertas enfermedades sistémicas. La enfermedad se presenta afectando a los tejidos que rodean el diente; su diagnóstico acertado es de gran importancia para su adecuado tratamiento y en especial en las etapas tempranas de la enfermedad. Los sistemas de clasificación son necesarios en orden de proveer un marco el cual científicamente estudia la etiología, patogénesis y el tratamiento en una forma ordenada. La Academia Americana de Periodoncia en 1999 realizó el taller sobre clasificación enfermedad periodontal, publicando una nueva clasificación, que está siendo adoptada por la mayoría de los odontólogos, y creemos que es importante que la demos a conocer y difundir para un mejor entendimiento de esta patología. La nueva clasificación divide a la enfermedad periodontal en: enfermedad gingival, periodontitis crónica, periodontitis agresiva, periodontitis como manifestación de enfermedad sistémica, enfermedad periodontal necrotizante, absceso periodontal, periodontittis asociada con lesiones endodónticas y las condiciones o deformidades del desarrollo adquiridas de los tejidos periodontales. Este artículo resume cada una de las anteriores entidades, exponiendo sus principales características para su diagnóstico

[Epulis in a newborn. histogenetic comparison with a granular cell tumor in adults]. / Epulis eines Neugeborenen. Histogenetischer Vergleich zum Granularzelltumor des Erwachsenen.

The congenital granular cell tumor is a rare lesion of newborns located on the alveolar ridge with a marked predilection for female infants. Histologically these tumors are characterized by large eosinophilic granular cells, similar to granular cell tumors in adults which are often seen as Abrikossoff tumors. Immunohistochemical studies revealed the different histogenesis and evolution of both these tumor entities. We report on a female newborn infant with a congenital epulis of the left anterior maxillary alveolar ridge. This case demonstrates a rare congenital tumor of newborns and reveals the histogenetic differences to granular cell tumors in adults.

[Focal palmoplantar and oral mucosa hyperkeratosis syndrome]. / Fokales palmoplantares und orales Mukosa-Hyperkeratose-Syndrom.

CASE REPORT: Four members of a family in three generations are presented who were affected by a rare syndrome (mucosa hyperkeratosis syndrome). This syndrome is characterized by autosomal-dominant inheritance, white lesions of the gingiva, and palmoplantar hyperkeratosis. The four affected members of the family revealed an abnormal keratinization of the gingiva and palmoplantar epidermis. Biopsies of plantar and gingival lesions histologically showed acanthosis and hyperkeratotic cornification of the epithelium. Electron microscopy demonstrated the features of epidermolytic hyperkeratosis. DISCUSSION: From the differential diagnostic point of view, the mucosa hyperkeratosis syndrome has to be distinguished from the Jadassohn-Lewandowsky syndrome and the Howel-Evans' syndrome, which is associated with esophageal carcinoma.

Kindler syndrome: a rare cause of desquamative lesions of the gingiva.

Kindler syndrome is a rare syndrome with cutaneous and intraoral manifestations. It has been suggested that there is an overlap between this syndrome and another called Weary syndrome. Only 68 cases of Weary and Kindler syndromes have been reported, with fewer solely attributed to Kindler syndrome. The salient cutaneous features are neonatal bullae, poikiloderma, photosensitivity, and acral atrophy. This article presents the clinical intraoral findings of two siblings of consanguineous descent diagnosed as having Kindler syndrome. Both had an erythematous and erosive appearance of the gingiva; one sibling had poor oral hygiene and a rapidly progressive form of periodontal disease; the other, whose oral hygiene was acceptable, had no detectable bone loss.

First case of surgical treatment of Farber's disease.

Farber's disease (Farber's lipogranulomatosis), which is inherited as an autosomal recessive trait, was first reported by Farber in 1952. We report a case of Farber's disease in a 12-year-old female. Her younger brother was affected with Farber's disease and died of it at 2 years of age. When she first presented, our patient's main clinical features were a shrill voice; subcutaneous nodules; contracture of the joints throughout the body; and granulomas of the oral cavity, the pharynx, and the upper and lower eyelids. Serial radiographs disclosed deformation of the joints throughout the body. Due to the granulomas in her oral cavity, she could take little food orally and therefore was malnourished. We performed a granulectomy under general anesthesia, and her difficulty with feeding and upper airway obstruction improved. There is no specific treatment for Farber's disease, and most patients reported have died by 2 years of age. This is the first reported patient with Farber's disease who has been surgically treated.

[Popliteal pterygium syndrome. A exceptional case]. / Syndrome des ptérygium poplités. Une observation privilégiée.

We report the case of a patient with a popliteal pterygium syndrome, a rare malformation associating, in its complete form, cleft lip and cleft palate, cleft lower lip, intergingival synechia, defects of the genito-urinary tract and popliteal pterygium. Based on this observation and a review of the literature, the phenotypic and genotypic aspects of this malformation were discussed together with adapted therapeutic management and genetic counselling.