FOU-dag UNN 23.05 2008 TAKO-senteret og forskning Kari Storhaug, dr. odont. Avdelingssjef TAKO-senteret Lovisenberg Diakonale sykehus

Internasjonale nettverk Eurordis: European organization for rare disorders IADH, International Association for Disability and oral Health NORD, National Organization for Rare Disorders, USA ED-network EB-network

Forskning Ektodermale dysplasier (Fak.) Williams syndrom (Fak.) Doktorgrad 2004 Williams syndrom (Fak.) Doktorgrad 2005 APS-1 (Ahus-Rikshospitalet) OI (TRS-Aker Sykehus) Sikleprosjekt - (LDS, Rikshospitalet, CP-foreningen) Prader Willi syndrom PWS - (Fak., PWS-foreningen) Doktorgradsprosjekt DiGeorge syndrom (Rikshospitalet) Treacher Collins syndrom

Hilde Nordgarden Thesis 2004 On Oligodontia, Ectodermal Dysplasias and Salivary Gland Development and Function Hilde Nordgarden Thesis 2004 My interest in medical conditions and salivary gland function dates back to the mid nineties, when I, as a dental student, became involved in a project regarding saliva in narcolepsy. During my work as a student research fellow I learnt much about salivary gland function and analyses of salivary secretions, and I became aware of the lack of research within the field. There are several diagnoses in which we, and others, have noticed a possible salivary gland dysfunction, but very little research has been done. I had several options when planning a project for a doctoral degree. I chose to concentrate on developmental disturbances of the ectodermal tissues and the result of my research so far is presented in the thesis “On oligodontia, Ectodermal Dysplasias and Salivary Gland Development and Function. So, why did I choose this topic? Before I answer that question I would like to define some terms.

Oligodonti Medfødt mangel av seks eller flere tenner, tredje molar ekskludert Prevalensen av oligodonti I befolkningen var ikke kjent The term oligodontia has been used to describe the congenital absence of several teeth. In this thesis the following definition is used: “Congenital absence of six or more teeth, third molars excluded”.

Ektodermal dysplasier Utviklingsforstyrrelser i to eller flere av følgende vev: Hår Tenner Negler Svettekjertler Freire-Maya and Pinheiro, 1984 Ectodermal dysplasias, or EDs for short, comprise a large and heterogeneous group of conditions, involving tissues derived from one of three embryonic germ layers, the ectoderm. The classical definition of ectodermal dysplasias is given by the Brazilian geneticists Freire-Maya and Pinheiro, and states that at least two of the following ectodermal tissues must be affected for an proper ED diagnosis to be made: Hair, teeth, nails and sweat glands.

Ektodermale dysplasier Tenner affisert hos 80% Oligodonti, en mikroform for ektodermal dysplasi? Mange udiagnostiserte tilfeller? As teeth are affected so often in EDs, dental health care personnel often meet these patients. The dental disturbances are in many cases their main problem, and extensive and lifelong treatment and maintenance are necessary. It has been claimed that oligodontia per see might represent a microform of ectodermal dysplasia. Furthermore, the experience at the TAKO-centre was that many patients with oligodontia presented signs and symptoms in extra-oral ectodermal tissues, but still had not been diagnosed with ectodermal dysplasias. We therefore hypothesised that there were many undiagnosed cases of EDs in Norway. Also, when searching databases we did not find studies regarding the prevalence of oligodontia in the population

Ektodermale dysplasier Spyttkjertler Redusert spyttsekresjon Tørre munnslimhinner Soppinfeksjoner In addition to the classical tissues generally regarded as the diagnostic ectodermal dysplasia tissues, the salivary glands also have ectodermal origin. Reduced salivary secretion and dry oral mucosa and as a result of this, fungal infections, had been mentioned in the literature, and the clinical impression within our group was that this was a problem in these patient groups.

Konklusjoner Assosiasjon mellom oligodonti og ekstraorale tegn og symptomer på ektodermal dysplasi Spyttkjertel dysfunksjon er et hyppig funn ved disse tilstandene – Oral ektodermal dysplasi Based on the performed studies we have made some main conclusions. Firstly, we conclude that there is an association between oligodontia and extra-oral signs and symptoms of ectodermal dysplasias. Secondly, we conclude that salivary gland dysfunction is a frequent finding in persons with oligodontia in combination with other symptoms from classical ectodermal dysplasia tissues. Our term Oral ectodermal dysplasia could be used on persons with oligodontia in combination with reduced salivary secretions. Reduced salivary secretion is often a serious problem for the person affected. Also oligodontia is a serious and demanding condition to treat. As oral ectodermal dysplasia could be present isolated, without extra-oral symptoms, we propose that this entity is included in the ectodermal dysplasia group. This would have practical implications for affected patients, providing a basis for adequate oral prophylaxis and treatment, and for Norwegian patients, a passport to having dental treatment costs fully covered by the Norwegian National Insurance Scheme.

Konklusjoner Utviklingsforstyrrelser av spyttkjertler ved ektodermal dysplasi Enkle spyttsekresjonstester bør gjøres hos personer med oligodonti / ektodermal The evidence of a impaired salivary gland development in x-linked hypohidrotic ectodermal dysplasia is growing stronger, both through the work presented here and through work by others. However, based on the nature of the ectodermal dysplasias we find it likely that impaired salivary gland development is the cause for the observed salivary dysfunction also in other forms of ectodermal dysplasias. We therefore advocate that simple salivary tests always should be performed in persons with oligodontia with or without extra-oral signs of the condition.

Variability of the cranial and dental phenotype in Williams syndrome Stefan Axelsson Thesis 2005

Avvik i tennene ved WS Manglende permanente tenner Små tenner Avvikende tannform Mellomrom mellom tennene Mineraliserings-defekter i tannemaljen Tann- og bittavvik

Delarbeide 6 Axelsson S, Bjørnland T, Kjær I, Heiberg A, Storhaug K Delarbeide 6 Axelsson S, Bjørnland T, Kjær I, Heiberg A, Storhaug K. Dental characteristics in Williams syndrome: a clinical and radiographic evaluation. Acta Odontol Scand 2003; 61: 129-136

40 % mangler én eller flere tenner 12 % mangler mer enn 6 tenner

Konklusjoner Størrelse og form på nevrokraniet avviker fra et normalmateriale Sella turcica viser stor variasjon i form og størrelse 3 områder i ansiktsskjelettet bidrar til det karakterisktiske utseende hos WS Ca. 40 % mangler én eller flere permanente tenner Ca. 12 % mangler MANGE permanente tenner Små permanente tenner Karakteristisk tannform på permanente fortenner

Autoimmunt polyendokrint syndrom type 1 (APS 1) Hovedkomponenter APS 1 Kronisk mukokutan kandidiasis Hypoparathyreoidisme Binyrebarksvikt 2 av disse komponentene kreves for å stille diagnosen

Delkomponenter APS 1 Gonadesvikt Diabetes mellitus type 1 Autoimmun thyreoideasykdom Pernisiøs anemi Malabsorpsjon Autoimmun hepatitt Ektodermal dysplasi

Kronisk mukokutan kandidiasis Vanligste ikke-endokrinologiske manifestasjon ved APS 1 (100%) Lesjoner fra angulær cheilitt til hypertrofiske eller atrofiske slimhinnelesjoner i munnhulen Candida infeksjon i negler er også vanlig

Emaljehypoplasier Permanente tenner Transverse hypoplastiske bånd Hypoplasi av større deler av emaljen Ses uavhengig av hypoparathyreoidisme

APS 1

Voksne med Osteogenesis imperfecta-OI og oral helse Del av en større studie, en populasjonsbeskrivelse av voksne med OI i Norge Studien ledes av dr. Lena L. Wekre på TRS/Sunnås sykehus Samarbeid med Aker sykehus – hjerteundersøkelse v/dr. Zoran R.

Orale symptomer ved OI Dentinogenesis imperfecta Malokklusjon Misfarging Frakturer Attrisjon Korte/atypiske røtter Klokkeformete kroner Obliterasjoner Apikale oppklaringer Malokklusjon

Dentinogenesis imperfecta-DI I litteraturen 28-50 % DI Ofte høyere frekvens ved de alvorlige formene av OI I undersøkelsesgruppen 18,5 % DI

Tann og bittavvik Dentalt underbitt i befolkningen i Skandinavia er ca 3 % I undersøkelsesgruppen: 10 % dentalt underbitt

Oral helse (manglende tenner) Gjennomsnitt 2.1 tenner Kontrollgruppen: 1.0 tenner

Oral helse (manglende tenner) Gjennomsnitt 5.0 tenner. Kontrollgruppen: 2.6 tenner

Sikling Kan være et betydelig problem hos barn og voksne med medfødte eller ervervede nevrologiske tilstander Patologisk sikling = sikling i våken tilstand etter 4 års alder

Sikling Sosiale problemer Hudproblemer Kostnader?

Årsaker til sikling Sjelden for mye saliva Saliva svelges ikke Nedsatt oral og peroral sensibilitet Nedsatt funksjon eller dysfunksjon av muskulaturen Anatomiske forhold Kroppsholdning

Behandling av sikling Tilrettelegge sittestilling og hodeposisjon Korrigere oral anatomi og dysfunksjon Orofacial trening Ganeplater Medikamenter Generelle Lokale|

Medikamenter Antikolinerge Egazil Skopolamin Botulinumtoksin A

Prosjekt: barn og unge med CP og et sikleproblem

Oral helse ved Prader-Willi syndrom TAKO-senteret Lovisenberg Diakonale Sykehus

Prader-Willi syndrom Generelle karakteristika: Hypotoni Spiseproblemer som spedbarn Senere overspising Behov for streng diett Vekstretardasjon

Prader-Willi syndrom Kraniofaciale karakteristika Smalt ansikt Buet panne Mandelformede øyne Nedadpekende munnviker Åpen,triangelformet munn Hypotoni

Prader-Willi syndrom Odontologiske karakteristika Saliva, seigt, tykt, redusert mengde Sterk tannslitasje (attrisjon/erosjon) Karies Utviklingsforstyrrelser i tannemalje Malokklusjon Forsinket tannfrembrudd

Prader-Willi syndrom Attrisjon/erosjon

Problemstillinger Er kvantitet og/eller kvalitet av saliva avvikende? Hvorfor slites tennene ned og hvor raskt? Hvor utbredt er karies? Forekomst av dentale utviklingsforstyrrelser Hvor vanlig er avvikende ganeform og malokklusjon ?

Målsetning Skaffe kunnskap omkring orale forhold ved PWS Kunnskap om salivas funksjon og spyttkjertlenes utvikling vil kunne klargjøre forhold omkring salivas rolle for tannslitasje og kariesutvikling generelt

Metode Intervju/klinisk undersøkelse Røntgen Gipsmodeller Fotografier OPG Laterale cephalogram BW Gipsmodeller Fotografier Analysere felte og ekstarherte tenner Analysere saliva

Nasjonalt samarbeid ØNH – Lovisenberg Diakonale Sykehus Det odontologiske fakultet Frambu PWS-foreningen

Dental and orofacial characteristics and functions in Treacher Collins syndrome

Dental and orofacial characteristics Use the parameters in The MHC Orofacial observation chart (Revised 2008) From Mun-H-centre, Gothenburg Download: mun-h-center.se Side 1 of 2

Collected data in the MHC- Database Mun-H-Centre, Gothenburg, Sweden A national database for documentation of orofacial manifestations in rare disorders Established in 1996 In January 2006, 1966 individuals were registered in the database Represent over 200 different rare disorders 45 different diagnoses presented on www.mun-h-center.se

Orofacial functions Nordic Orofacial Test-Screening (NOT-S) Consisting of Screening form Picture manual

NOT-S in current studies Ectodermal dysplasia 55 persons in USA and Sweden Birgitta Bergendal, Spec. in Prosthetic Dentistry and Anita McAllister, Dr. med., SLP Prader Willi syndrome 30 children and adolescents TAKO-centre, Rønnaug Sæves, Spec. in Paeditric Dentistry Muscular dystrophias Mun-H-centre, Lotta Sjögreen, SLP Prematurely born children In schoolage Oulu university, Anneli Yliherva, SLP

Reference Bakke M, Bergendal B, McAllister A, Sjögreen L, Åsten P. Development and evaluation of a comprehensive screening for orofacial dysfunction. Swedish Dental Journal 2007;31:75-84. Download: www.mun-h-center.se

Treacher Collins syndrome Orofacial characteristics and functions Project outline Speech and language pathologist Pamela Åsten Spec. in paediatric dentistry Nina Skogedal TAKO-centre, Oslo Supervisors: Kari Storhaug, PhD, TAKO-centre Anita McAllister, PhD, University of Linköping Lotta Sjøgreen, SLP, Mun-H-Center

Population Persons with TCS in Norway Recruited via TAKO-centre Dept. for medical genetics, Rikshospitalet Craniofacial team, Rikshospitalet SSD (centre for rare disorders), Rikshospitalet Norwegian Craniofacial parent organisation

Population TAKO-centre 23 registered patients 3 families 13 female and 10 male Born from 1931 to 2003 From different parts of Norway 4 known relatives

Study parameters Assessment by clinical geneticist Intraoral relations Salivary glands and saliva secretion Orofacial functions Conditions in nose and pharynx Respiration and sleep Hearing Vision Quality of life and functional outcome

Assessment by clinical geneticist Ketil Heimdal, Dept. of medical genetics, Rikshospitalet Interview Assessment of clinical features Medical severity score

Intraoral relations Review of former dental interventions Nina Skogedal, TAKO-centre, LDS Review of former dental interventions Oral health habits Teeth Mineralisation Agenesis Occlusion Oral health Caries Periodontal status Review of present dental arrangements

Salivary secretion Measuring of salivary secretion Nina Skogedal. TAKO-senteret, LDS Measuring of salivary secretion

Salivary glands Dept. of ENT, LDS Ultrasound examination of salivary glands Hypoplasia, agenesia?

Conditions in nose and pharynx Dept. of ENT, LDS Clefts Nasal passage ( choanalatresia) Velopharyngeal conditions

Orofacial functions Oral motor function Eating and drinking Pamela Åsten, TAKO-centre, LDS Oral motor function The MHC Orofacial observation chart The MHC Questionnaire NOT-S Eating and drinking Structured observation Speech, resonance and voice Svensk Artikulations och Nasalitets Test (SVANTE) Estimated time: 3 hours

Respiration and sleep Review of former and current Dept. of ENT, LDS Review of former and current measures concerning respiration Sleep apnea registration

Hearing Dept. of ENT, LDS (Ullevål University Hospital) Audiogram

Quality of life Living with family Network and friends Amy Østertun Geirdal, Høgskolen i Oslo Living with family Network and friends Social insurance system etc. Earlier special educational programs School and education Professional life

Project period: May 2008 – June 2009 May – July 2008 Application to ethical committee Discussions with co-workers Recruitment of participants August – September 2008 Written information for children and adults Development of full protocol October 2008 – January 2009 Collecting data February – June 2009 Data assessment Scientific article