Van der Woude syndrome

Van der Woude syndrome
SpecialtyMedical genetics Edit this on Wikidata

Van der Woude syndrome (VDWS) is a genetic disorder characterized by the combination of lower lip pits, cleft lip with or without cleft palate (CL/P), and cleft palate only (CPO).[1] The frequency of orofacial clefts ranges from 1:1000 to 1:500 births worldwide, and there are more than 400 syndromes that involve CL/P.[2] VWS is distinct from other clefting syndromes due to the combination of cleft lip and palate (CLP) and CPO within the same family. Other features frequently associated with VWS include hypodontia in 10-81% of cases, narrow arched palate, congenital heart disease, heart murmur and cerebral abnormalities, syndactyly of the hands, polythelia, ankyloglossia, and adhesions between the upper and lower gum pads.[3]

The association between lower lip pits and cleft lip and/or palate was first described by Anne Van der Woude in 1954. The worldwide disease incidence ranges from 1:100,000 to 1:40,000.[4]

Genetics

Van der Woude syndrome is inherited as an autosomal dominant disease caused by a mutation in a single gene with equal distribution between the sexes. The disease has high penetrance at about 96% but the phenotypic expression varies from lower lip pits with cleft lip and cleft palate to no visible abnormalities.[2][4] Approximately 88% of VWS patients display lower lip pits, and in about 64% of cases lip pits are the only visible defect. Reported clefting covers a wide range including submucous cleft palate, incomplete unilateral CL, bifid uvula, and complete bilateral CLP. VWS is the most common orofacial clefting syndrome, accounting for 2% of CLP cases.[3]

The majority of VWS cases are caused by haploinsufficiency due to mutations in the interferon regulatory factor 6 gene (IRF6) on chromosome 1 in the 1q32-q41 region known as VWS locus 1. A second, less common, causative locus is found at 1p34, known as VWS locus 2 (VWS2). More recent work has shown that GRHL3 is the VWS2 gene. Grhl3 is downstream of Irf6 in oral epithelium, suggesting a common molecular pathway leading to VWS. Prior work also suggested WDR65 as a candidate gene.[4][5] IRF6 contains two non-coding and seven coding exons and is part of a family of nine transcription factors with a highly conserved helix-turn-helix DNA binding domain called the Smad-interferon regulatory factor binding domain (SMIR). Mutations in coding or non-coding IRF6 exons can result in Van der Woude syndrome.[2] Due to the wide range of expressivity, it is also believed that other unidentified loci contribute to disease development.[4]

An example of the clear phenotypic variability is a monozygotic twin study conducted by Jobling et al. (2010). Two monozygotic female twins had the same IRF6 mutation; however Twin A was born with a bilateral cleft lip, whereas Twin B had bilateral lip pits and no orofacial clefting. Both twins were diagnosed with VWS. The twins' father had lip pits alone and a family history of CLP, CP, CL, and/or lip pits. Both twins were diagnosed with VWS. Polymerase chain reaction (PCR) amplification was done for all exons of IRF6, and a missense mutation was discovered in exon 4. The tyrosine in the normal protein at this position is conserved across mammals, frogs, and chickens, so despite the fact that it was a previously unreported mutation, it was expected to be deleterious. This study is not the first case of different phenotypes occurring between monozygotic twins. Possible causes of phenotypic variability include variations in the intrauterine environment, epigenetic differences, or chance effects.[6]

Pathophysiology

Lip pits were first reported in 1845 by Demarquay who thought they were indentations made by the upper incisors. Today it is known that they occur during embryogenesis due to IRF6 mutations. On day 32 of embryonic development there are four growth centers of the lower lip divided by two lateral grooves and one median. By day 38 of normal development, the grooves have disappeared. However, when growth of the mandibular process is impeded, a lip pit occurs. Lip pits begin to develop on day 36. Cleft lip begins to develop on day 40, and cleft palate emerges on day 50 of development.[3]

There are three types of lip pits, which are classified according to their location: midline upper, comissural, and lower lip. The most common phenotype is two symmetrical lower lip pits flanking both sides of the midline in the bilateral paramedial sinuses. Lower lip pits may also be bilaterally, unilaterally, or medially asymmetrical. The occurrence of a single lip pit is considered incomplete expression, and it typically occurs on the left side of the lower lip. There are also three different shapes for lip pits, the most common being circular or oval; less common forms include slit-like or transverse. The lip pits extend into the orbicularis oris muscle, ending in blind sacs surrounded by mucous glands. In some cases mucus is excreted when the muscles contract.[3]

Diagnosis

Clinical diagnosis based on orofacial clefts and lip pits typically occurs shortly after birth. Certain defects may be difficult to diagnose, particularly a submucous cleft palate. This form of CP may not be detected except through finger palpation, as the mucosa covering the palate is intact, but the muscles underneath have lost their proper attachments. Feeding problems, impaired speech, and hearing loss are symptoms of a submucous cleft palate.[4] Furthermore, approximately 15% of VWS cases with orofacial clefts, in the absence of prominent lip pits, cannot be easily distinguished from non-syndromic forms of orofacial clefting.[7] Therefore, it is very important to closely examine these patients as well as their relatives for lip pits, especially when there is a family history of mixed clefting, in order to make the VWS diagnosis.[3] Dentists may also play an important role in diagnosing cases not detected at birth, as they detect hypodontia commonly associated with VWS. The patients most commonly lack the upper second premolars followed by the lower second premolars and upper lateral incisors. The absence of these teeth might play a role in the constricting of the dental arches.[3][4]

The clinical signs seen in VWS are similar to those of popliteal pterygium syndrome (PPS), which is also an autosomal dominant disease. Approximately 46% of affected individuals have lip pits; other features include genital abnormalities, abnormal skin near nails, syndactyly of fingers and toes, and webbed skin. The disease is also caused by mutations in IRF6; however, they occur in the DNA-binding domain of IRF6 and result in a dominant negative effect in which the mutated IRF6 transcription factor interferes with the ability of the wild type copy to function, in the case of a heterozygous individual.[2]

Genetic Counseling

Genetic counseling for VWS involves discussion of disease transmission in the autosomal dominant manner and possibilities for penetrance and expression in offspring.[3] Autosomal dominance means affected parents have a 50% chance of passing on their mutated IRF6 allele to a their child. Furthermore, if a cleft patient has lip pits, he or she has a ten times greater risk of having a child with cleft lip with or without cleft palate than a cleft patient who does not have lip pits.[4] Types of clefting between parents and affected children are significantly associated; however, different types of clefts may occur horizontally and vertically within the same pedigree. In cases where clefting is the only symptom, a complete family history must be taken to ensure the patient does not have non-syndromic clefting.[3]

Treatment

Lip pits may be surgically removed either for aesthetic reasons or discomfort due to inflammation caused by bacterial infections or chronic saliva excretion, though spontaneous shrinkage of the lip pits has occurred in some rare cases. Chronic inflammation has also been reported to cause squamous-cell carcinoma. It is essential to completely remove the entire lip pit canal, as mucoid cysts can develop if mucous glands are not removed. A possible side effect of removing the lip pits is a loose lip muscle. Other conditions associated with VWS, including CL, CP, congenital heart defects, etc. are surgically corrected or otherwise treated as they would be if they were non-syndromic.[3]

References

  1. ^ "Van der Woude syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17.
  2. ^ a b c d Malik S, Kakar N, Hasnain S, Ahmad J, Wilcox ER, Naz S (2010). "Epidemiology of Van der Woude syndrome from mutational analyses in affected patients from Pakistan". Clinical Genetics. 78 (3): 247–256. doi:10.1111/j.1399-0004.2010.01375.x. PMID 20184620. S2CID 205407851.
  3. ^ a b c d e f g h i Rizos M, Spyropoulos MN (2004). "Van der Woude syndrome: a review. Cardinal signs, epidemiology, associated features, differential diagnosis, expressivity, genetic counselling, and treatment". European Journal of Orthodontics. 26 (1): 17–24. doi:10.1093/ejo/26.1.17. PMID 14994878.
  4. ^ a b c d e f g Lam AK, David DJ, Townsend GC, Anderson PJ (2010). "Van der Woude syndrome: dentofacial features and implications for clinical practice". Australian Dental Journal. 55 (1): 51–58. doi:10.1111/j.1834-7819.2009.01178.x. PMID 20415912.
  5. ^ [1], OMIM Van der Woude Syndrome 2
  6. ^ Jobling R, Ferrier RA, McLeod R, Petrin AL, Murray JC, Thomas MA (2011). "Monozygotic twins with variable expression of Van der Woude syndrome". American Journal of Medical Genetics. 155A (8): 2008–2010. doi:10.1002/ajmg.a.34022. PMC 3140610. PMID 21739575.
  7. ^ Salahshourifar I, Sulaiman WA, Halim AS, Zilfalil BA (2012). "Mutation screening of IRF6 among families with non-syndromic oral clefts and identification of two novel variants: review of the literature". European Journal of Medical Genetics. 55 (6–7): 389–393. doi:10.1016/j.ejmg.2012.02.006. PMID 22440537.

Read other articles:

Artikel ini sebatang kara, artinya tidak ada artikel lain yang memiliki pranala balik ke halaman ini.Bantulah menambah pranala ke artikel ini dari artikel yang berhubungan atau coba peralatan pencari pranala.Tag ini diberikan pada November 2022. Elemér ThuryLahir3 April 1874MezőtúrMeninggal21 Juni 1944BudapestPekerjaanPemeranTahun aktif1912-1944 Elemér Thury (3 April 1874 – 21 Juni 1944) adalah seorang pemeran film Hungaria. Ia tampil dalam 14 film antara 1912 dan 194...

 

Sport facility in Gdańsk/Sopot, Poland ERGO ARENAFormer namesHala Gdańsk-SopotLocationplac Dwóch Miast 1, 80-344 Gdańsk / Sopot, PolandCoordinates54°25′33″N 18°34′49″E / 54.42583°N 18.58028°E / 54.42583; 18.58028OperatorHala Gdańsk-Sopot Sp. z o.o.Executive suites940 (seating)Capacity15,000 (concerts: Seating and standing) 11,409 (seating only)Field size96m x 30m x 48mConstructionBroke ground2007OpenedAugust 18, 2010Construction costPLN zł 251 million...

 

American politician from North Carolina RepresentativeLarry BrownMember of the North Carolina House of Representativesfrom the 73rd districtIn officeJanuary 1, 2005 – August 16, 2012Preceded byMichael Decker (Redistricting)Succeeded byJoyce Krawiec[1] Personal detailsBorn(1943-02-09)February 9, 1943[2]Winston-Salem, North CarolinaDiedAugust 16, 2012(2012-08-16) (aged 69)Pinehurst, North CarolinaPolitical partyRepublicanResidenceKernersville, North C...

TBL1Y Ідентифікатори Символи TBL1Y, TBL1, transducin (beta)-like 1, Y-linked, transducin beta like 1, Y-linked, transducin beta like 1 Y-linked, DFNY2 Зовнішні ІД OMIM: 400033 HomoloGene: 129986 GeneCards: TBL1Y Онтологія гена Молекулярна функція • GO:0001106 transcription corepressor activity Клітинна компонента • histone deacetylase complex• клітинне ядро Біологічний процес •...

 

Ця стаття є частиною Проєкту:Військова історія (рівень: 4, важливість: середня) Портал «Війна»Мета проєкту — створення якісних та інформативних статей на теми, пов'язані з війною. Ви можете покращити цю статтю, відредагувавши її, а на сторінці проєкту вказано, чим ще можна д

 

هذه المقالة يتيمة إذ تصل إليها مقالات أخرى قليلة جدًا. فضلًا، ساعد بإضافة وصلة إليها في مقالات متعلقة بها. (فبراير 2019) روجر هدسون معلومات شخصية الميلاد 8 يونيو 1967 (56 سنة)  الجنسية المملكة المتحدة  المدرسة الأم كلية كيبل  [لغات أخرى]‏  الحياة العملية الفرق نادي ال

Andy GarcíaGarcía tại Liên hoan phim Mỹ Deauville (2009)SinhAndrés Arturo García Menéndez12 tháng 4 năm 1956 (67 tuổi)La Habana, CubaNghề nghiệpDiễn viênNăm hoạt động1978–nayPhối ngẫuMarivi Lorido Garcia (1982-nay) Andrés Arturo García Menéndez (sinh 12 tháng 4 năm 1956), thường được biết đến với tên Andy García, là một diễn viên Mỹ gốc Cuba. Ông trở nên nổi tiếng trong những năm cuối 1980 và 1990, và đã xu...

 

Хосе Мануель Морено Хосе Мануель Морено Особисті дані Повне ім'я Хосе Мануель Морено Фернандес Народження 3 серпня 1916(1916-08-03)   Буенос-Айрес, Аргентина Смерть 26 серпня 1978(1978-08-26) (62 роки)   Буенос-Айрес, Аргентина Зріст 178 см Вага 72 кг Громадянство  Аргентина Позиція п

 

Shaman GenreRole-playing gamesPublisherTSRPublication date1995 Shaman is an accessory for the 2nd edition of the Advanced Dungeons & Dragons fantasy role-playing game, published in 1995. Contents Shaman details the shaman character class, which calls upon spirits to ask them for magic in the form of favors; these are not undead, but rather they are spirits of anything from the living world including that of nature or of ancient ancestors.[1] Unlike other types of magic, favors can...

German theologian Wilhelm HerrmannJohann Georg Wilhelm Herrmann (1846-1922), Lutheran German theologianBornJohann Georg Wilhelm Herrmann(1846-12-06)6 December 1846MelkowDied2 January 1922(1922-01-02) (aged 75)Marburg an der LahnOccupation(s)Professor, theologianNotable workThe Communion of the Christian with GodTheological workLanguageGermanTradition or movementLutheran, LiberalismMain interestsIdealism Johann Georg Wilhelm Herrmann (6 December 1846 – 2 January 1922) was a Lutheran Ger...

 

Letak Voyager 1 dan 2 (2005). Heliosheath (bahasa Indonesia: selubung surya) adalah zona antara gelombang kejut (termination shock) dan heliopause di perbatasan luar tata surya. Zona ini berada di sepanjang pinggiran heliosfer, sebuah gelembung yang disebabkan oleh angin surya. Jaraknya diperkirakan sekitar 80 hingga 100 unit astronomi (AU) dari matahari. Misi penjelajah luar angkasa Voyager 1 dan Voyager 2 saat ini termasuk meneliti heliosheath tersebut. Pada Mei 2005, dilaporkan bahwa Voyag...

 

Syed Hasan Imamসৈয়দ হাসান ইমামBorn (1935-07-27) 27 July 1935 (age 88)Bardhaman, Bengal Presidency, British IndiaNationalityBangladeshiOccupation(s)Actor, film director, television directorSpouse Laila Hasan ​(m. 1965)​[1]AwardsEkushey PadakIndependence Day Award Syed Hasan Imam (born 27 July 1935) is an actor, film director, television director and cultural personality in Bangladesh.[2] He earned Ekushey Padak (199...

2005 fighting video game This article's lead section may be too short to adequately summarize the key points. Please consider expanding the lead to provide an accessible overview of all important aspects of the article. (May 2013) 2005 video gameTekken 5: Dark ResurrectionNorth America cover of the PSP version depicting Jin Kazama and Devil JinDeveloper(s)NamcoEighting (PSP)Publisher(s)Namco[a]Director(s)Katsuhiro HaradaProducer(s)Katsuhiro Harada SeriesTekkenPlatform(s)Arcade, P...

 

Genus of flatworms Matuxia Matuxia tymbyra Scientific classification Domain: Eukaryota Kingdom: Animalia Phylum: Platyhelminthes Order: Tricladida Family: Geoplanidae Subfamily: Geoplaninae Genus: MatuxiaCarbayo et al., 2013 Type species Geoplana tuxauaE. M. Froehlich, 1955 Matuxia is a genus of land planarians from Brazil. Description The genus Matuxia is characterized by having a slender body with nearly parallel margins, reaching up to 12 cm in length, and being slightly convex on bot...

 

Closed US military installation This article includes a list of references, related reading, or external links, but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. (December 2012) (Learn how and when to remove this template message) Grand Rapids Air Force Station Part of Air Defense Command (ADC)Grand Rapids AFSLocation of Grand Rapids AFS, MinnesotaCoordinates47°14′25″N 93°30′54″W / &#x...

Veronica is a brand name of successive Dutch commercial and public radio and television broadcasters. It began its life as an offshore radio station, Radio Veronica, on 17 May 1960. The name comes from its first name VRON – Vrije Radio Omroep Nederland (Dutch for 'Free Radio Station [of the] Netherlands'). Free was a reference to the laws at the time that didn't allow commercial radio broadcasters to operate from a location within the (land) territory of the Netherlands. Though Vero...

 

American singer Tony DizeBackground informationBirth nameTony Feliciano RiveraAlso known asLa Melodía de la CalleBorn (1982-05-31) May 31, 1982 (age 41)Boston, Massachusetts, U.S.[1]GenresReggaetonOccupation(s)SingerYears active2003–presentLabelsWYMachetePinaSony LatinMusical artist Tony Feliciano Rivera (born May 31, 1982), better known by stage name Tony Dize, is an American singer of Puerto Rican descent. His first recorded performance was from the album Blin Blin, Vol. 1, ...

 

Indian chess player (born 1994) Darpan InaniCountryIndiaBorn (1994-02-14) February 14, 1994 (age 29)Vadodara, Gujarat, IndiaTitleBronze at World Junior chess Championship for blind (2013)Peak rating2135 (January 2020) Darpan Inani is a prolific blind Indian chess player and a Chartered Accountant from Vadodara. He is currently the highest-rated visually impaired chess player in India, with an ELO rating of 2135 as of January 2020.[1] He won a bronze medal on his respective b...

Данная статья — часть обзора История математики. Научные достижения индийской математики широки и многообразны. Уже в древние времена учёные Индии на своём, во многом оригинальном пути развития достигли высокого уровня математических знаний. В I тысячелетии н. э. и...

 

2014 American filmSuburban GothicTheatrical release posterDirected byRichard Bates Jr.Written byRichard Bates Jr.Mark BrunerProduced byDylan Hale LewisStarringMatthew Gray GublerKat DenningsCinematographyLucas Lee GrahamEdited bySteve AnsellYvonne ValdezMusic byMichl BritschProductioncompanyNew Normal FilmsDistributed byFilmbuffRelease dates July 19, 2014 (2014-07-19) (Fantasia Festival) January 30, 2015 (2015-01-30) (United States) Running time90 minutes...

 

Strategi Solo vs Squad di Free Fire: Cara Menang Mudah!