Van Der Woude Syndrome

Submit Manuscript | http://medcraveonline.com by a mutation to interferon regulatory factor 6 on chromosome I [2]. They describe a unique case of the two syndromes occurring concurrently though apparently independently in a girl with Van der Woude syndrome and pituitary insufficiency associated with clefts before correctly diagnosing Turner syndrome [2]. Typical blind fistulas of the lower lip, combined with bilateral cleft upper lip and palate. Cleft, lips, alveolar ridges and palates are among the most common birth defects. The cleft occurrence is result of interaction of multiple genes and environmental factors. Several thousand of different discovered mutations are responsible for syndromes, but still numerous phenotypic cases are of unknown genetic origin. Today easier access to genetic counseling and the lower cost of DNA testing can lead to new findings on the causes of complex malformations [3]. The Interferon Regulatory Factor 6 gene has been associated with syndromic and nonsyndromic orofacial clefts. Gowans LJ et al. [4] carried out Sanger Sequencing on DNA from184 patients with nonsyndromic orofacial clefts and 80 individuals with multiple congenital anomalies that presented with orofacial clefts. They sequenced all the nine exons of IRF6 as well as the 5’ and 3’ untranslated regions. Their results show that exons 4 and 7 of IRF6 are mutational ‘hotspots’in sub-Saharan Africans cohort. In Africa population, prevalent of the porofacial clefts with variable penetrance and expressivity is induced by IRF6 mutants. Their observations are relevant for detection of high-risk families as well as genetic counseling [4]. The etiology of nonsyndromic cleft palate remains elusive, but it has been suggested that causative genes of syndromic CL/P might also contribute to NSCL/P. Recently, GRHL3 was identified as another VWS causative gene. Thus, it may be a novel candidate gene for NSCL/P. In the study by Wang Y et al, they genotyped 10 tag SNPs covering GRHL3 and performed association analysis with NSCL/P in 504 cases and 455 healthy controls. They also stated that further, the robustness of association between GRHL3 and NSCL/P should be further validated in expanded cohorts [5]. Common to van der Woude and Popliteal pterygium syndrome syndromes is that they are autosomal dominantly inherited disorders caused by heterozygous mutations in IRF6. Busche A et al. [6] present a three generation family with tremendous intrafamilial phenotypic variability. The newborn index patient had a diagnosis of popliteal pterygium syndrome. The mother presented with a classic Van der Woude Syndrome, while the maternal grandfather had Van der Woude Syndrome as well as minor signs of popliteal pterygium syndrome. In all three affected the known pathogenic mutation c.265A>G, p.Lys89Glu in IRF6 was identified. While interas well as intra-familial variability has been described in IRF6-related disorders, the occurrence of a typical Van der Woude Syndrome without any other anomalies as well as a diagnosis of Popliteal pterygium syndrome in the same family is rare [6].