vertical dimension 2

8/13/2019 vertical dimension 2

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Deve lopment o f the Vert ica l Dimens ionNature and NutureJames K. Hartsfield Jr

The relevance of analyzing the dev elop men t of the vert ical dimension toclinical practice is first to det erm ine if there is a vertical dim ens ion com po-nent to the malocclusion, then ascertain what factors are having the great-est inf luence on the vert ical dimensio n problem . U nfortuna tely, studies onthe genetic and environmental factors that inf luence the development ofvert ical dimension are representative of the samples, not necessari ly of anyparticular individual. In addition, the extent that a particular trait is influ-enced by genetic factors may have little if any effect on success of environ-mental treatment) intervention. Gen etic factors that inf luenced a trai t mayalso inf luence the response to intervention to al ter that trai t , or othergenetic factors may be involved in the response. Therefore, th e possibi l i tyfor altering the environ men t to gain a more favorable dimens ion is theoret-ically possible, even in individuals with a relatively high genetic influence onthe vert ical dimension. Ho wever, th e question of how en vironm ental andgenetic factors interact a question that essential ly cannot be answere d inestimates of heritabi l i ty), is most relevant to cl inical practice because i t mayexplain wh y a part icular al terat ion of the environ men t treatmen t) in onecomp liant patient m ay be successful and not in another. Semin Ortho d2002;8:113-119.) Cop y r i g h t 2002 , E l se v i e r Sc i e n ce USA ) . A l l r i g h t s r e ser ve d .

o n s i d e r a t i o n o f f a c t o r s t h a t i n f l u e n c e , d e -t e r m i n e , o r e v e n d r i v e d e v e l o p m e n t u s u a l l y

i nvo l ves a d i scuss i on o f na t u re ve r sus nu r t u r e , asi f t hey were m u t ua l l y exc l us i ve . How ever , deve l -o p m e n t i s n o t t h e r e s u l t o f g e n e t i c a n d e n v i r o n -m e n t a l n o n g e n e t i c ) f a c t o r s w o r k i n g i n i s o l a ti o no r i n d e p e n d e n t o f o n e a n o t h e r . B e f o r e p r o c e e d -i n g , a c o u p l e o f b a s ic d e f i n i t i o n s a r e r e q u i r e d .G e n o t y p e g e n e r a l l y r e f e r s to t h e s e t o f g e n e s t h a tan i nd i v i dua l car r i es and , i n par t i cu l a r , u sua l l yrefe r s to t he par t i cu l a r pa i r o f a l l e les a l t e rna t i vef o r m s o f a p a r ti c u l a r g e n e ) a t a g i v e n r e g i o n o ft h e g e n o m e . I n c o n t r a s t , p h e n o t y p e i s t h e o b -s e r v a b l e p r o p e r t i e s a n d p h y s i c a l c h a r a c t e r i s t i c so f a n i n d i vi d u a l, 1 a s d e t e r m i n e d b y g e n o t y p e

l~}rmz the Indiana University hool of Dentistu, Indianapo lis,IN.

Address correspondence to James K . Hartsfield, Jr, DM D, MS ,MMedSci, Ph D, Indiana University School of Dentistry, 11 21 WMichigan, IrMianapolis, IN 46202-5186.Copyright 2002, Elsevier Science (USA). All *Jghts *~served.1073-8746/02/0803-0002535.00/0doi: 10.1053/sodo. 2002.125430

a n d t h e e n v i r o n m e n t i n w h i c h t h e i n d iv i d u a ldeve l ops .

E v e n G e n e M u t a t i o n s F o r D o m i n a n tT r a i t s A r e N o t P r e d e t e r m i n i n gT h e c r a n i o s y n o s t o si s s y n d r o m e s a l o n g w i t ht h e i r e f f e c t o n c r a n i o f a c i a l g r o w t h a n d d e v e l o p -m e n t ) a r e a u t o s o m a l d o m i n a n t t r a i t s a s s o c i a t e dw i t h s i n g l e - g e n e m u t a t i o n s . T h e y p r o v i d e g o o de x a m p l e s o f h o w , e v e n w i t h t h e s t r o n g i n f l u e n c eo f a si n g le g e n e , t h e p h e n o t y p e c a n v a r y m a r k -e d l y . C o n t r a r y t o a n e a r l i e r p r e s u m p t i o n t h a t ap a r t i c u l a r m u t a t i o n i n a g i v e n g e n e w o u l d a l w a ysresu l t i n a spec i f i c syndrome, severa l i den t i ca lm u t a t i o n s i n t h e f i b r o b l a s t g r o w t h f a c t o r r e c e p -t o r 2 g e n e h a v e b e e n f o u n d i n p a t i e n t s d i a g -n o s e d w i t h t h e t h r e e c l in i c al e n t i t ie s o f C r o u z o n ,Pfe i f f e r , an d J ackson-W ei ss syn drom e. 2,-~

A n o t h e r e x a m p l e o f t h e i n d i v i d u a l v a r ia b i li t yo f t h e s e a u t o s o m a l d o m i n a n t p h e n o t y p e s a s so c i-a t e d w i t h a s i n g l e - g e n e m u t a t i o n o c c u r r e d i ni nd i v i dua l s wi t h t he c l ass i c pheno t ypes o fP f e i f fe r a n d A p e r t s y n d r o m e , a s w e ll a s i n s e v e n

Semina rs in Orthodontics, Vol 8, No 3 (September), 2 002 : pp 113 -119 3


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other individuals with a facial resemblance toCrouzon syndrome that occurred in the samefamily. 4 The phe noty pe may be so variable thatan individual may appea r to be clinically norma lyet have the same gene mutat ion associated withCrouzon syndrome in three of his children an dtwo of his grandchildren. Only through cepha-lometry was a minimal expression o f featuressuggestive o f Cr ouzo n syndr ome evident. 5

The phenotypic variation present in these ex-amples may be caused by modifying factors suchas envi ronme nt and other modifying) genes inthe ge nom e that interact with the effect of aspecific mutation associated with a dominanttrait. In fact, the conc epts of variable expressivityand reduced penetrance are applied to domi-nant traits or conditions, acknowledging the po-tentially variable phenotype that may not be ev-ident at all in an individual with the genemutation 3 ~These examples give a clear messagethat even for a generally extreme autosomaldominant phenotype, simply discovering thegene mutation will very likely indicate that therewill be an effect on craniofacial growth and de-velopmen t, bu t it does not give a precise pictureof what that effect will be only what it may tendto be.

E s t i m a t i n g t h e I n f l u e n c e o f G e n e t i c a n dE n v i r o n m e n t a l F a ct o rs o n P h e n o t y p eA discussion of the methods and assumptionsmade to estimate heritability, defined as the pro-porti on o f the total phenoty pic variance in asample that is contr ibute d by genetic variance, vis beyond the scope of this article. For moreinformation on these meth ods and assumptions,the reader may start with Genetics and Analysis ofQuantitative Traits by Lync h a nd Walsh. s A traitwith a heritability of 1 is said to be expressedwithout any enviromnental influence, whereas atrait with a heritability of 0.5 would have half itsvariability from individual to individual) influ-enced by environmental factors and half by ge-notypic factors. Values over 1 may occur becausethe twin met hodo logy provides an estimate ofheritability, under several simplifying assump-tions, that may be inco rrect. Still, the estim ationof heritability can provide an indication of therelative im porta nce of genetic factors. Confirm-ing that there is a certain degr ee of geneticinfluence on a trait is a preliminary step to fur-

ther specific genetic linkage studies using DNAmarkers) to deter mine areas of the genom e thatappear to be associated with the characteristicsof a given trait. 9

A few points should be kept in mind whenreviewing heritability estimates. First of all, theyrefer to a specific sample and do not necessarilypertain to a given individual even from withinthe sample. Thus, they do not allow one to tell towhat degree a particular trait was determined bygenetic or environmental factors in a single in-dividual. In addition, heritability estimates aredescriptive of variances within a sample at agiven time, a nd they are not predictive. 9 Herita-bility estimates can change with age; for exam-ple, a longitudinal analysis of 30 sets of siblingsthat had not undergone orthodontic treatmentshowed a significant increase in heritability esti-mates between the ages of 4 and 14 years for 29craniofacial skeletal variables, including in-creases for total anterior face height, upper an-terior face height, total posterior face height,and upper posterior face height. Despite thegeneral trend for all the craniofacial skeletalvariables to increase, there was a decrease forlower posterior face height. When a comparisonwas made of the craniofacial skeletal heritabilityestimates at age 14 years and 20 years, there wasan insignificant upward trend for some of thetraits. However, there was a decrease in the her-itability estimate from the age of 14 for upperanterior face height and an increase for lowerposterior face height to that estimated at age 4years. 1

The heritability o f a trait c ann ot necessarilybe extrapolated from one sample and set ofenviro nmenta l conditions to an other. 7 An ad-verse environment can alter the phenotypic ex-pression that the genes would have promotedunder more favorable conditions. An extremeexample of this principle is the delayed growthseen fro m the effects of famine associated withwar. n T here fore , a high heritability does n otprevent a trait from being substantially influ-enced by subsequent changes in environmentalconditions in that sample.12

E s t i m a t i o n O f V e r ti c al D i m e n s i o nH e r i t a b i l i t y

linical consideration of the vertical dimensionmay include the evaluation of the ratio of the


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u p p e r a n t e r i o r f a c e h e i g h t t o l ow e r a n t e r i o r f a c eh e i g h t , a s w e l l as a n t e r i o r t o p o s t e r i o r f a c eh e i g h t s , h w e s t i g a t i o n o f t h e a n t e r i o r u p p e r f a c eh e i g h t t o a n t e r i o r l o w e r f a c e h e i g h t i n 3 0m o n o z y g o t i c t wi n p a i r s r a n g i n g i n a g e f r o m12 .0 t o 18 .8 year s , w i t h a mean o f 15 .9 year s ) ,and 30 d i zygo t i c l i ke-sex t wi n pa i r s r ang i ng i nage f rom 12 .4 t o 21 .0 year s , w i t h a mean o f 15 .5year s ) r esu l t ed i n a her i t ab i l i t y es t i mat e o f0 .52? 3

L a t e r a l c e p h a l o g r a p h s o f 33 m o n o z y g o t i c a n d46 d i zygo t i c t wi ns , who r anged i n age f rom 9 t o1 6 y e a r s m e a n , 1 2 .1 y e a r s) a n d h a d n o t u n d e r -g o n e o r t h o d o n t i c t r e a t m e n t , w e r e u s e d i n g e -n e t i c m o d e l f i t t i n g t o d e t e r m i n e t h e h e r i t a b i l i t yo f a n t e r o p o s t e r i o r a n d v e r t ic a l f a c ia l p r o p o r -t i ons . 14 Th e ana l ys is i nd i ca t ed t ha t add i t i veg e n e s a n d t h e s p e c i f i c e n v i r o n m e n t i n f l u e n c e da l l t he f ac i a l p rop or t i o ns . Th e h er i t ab i l i t y was0 .7 1 f o r u p p e r t o l o w e r a n t e r i o r f a c e h e i g h t a n d0 . 6 6 f o r a n t e r i o r t o p o s t e r i o r f a c e h e i g h t .

T h e b e t t e r - f i t t i n g m o d e l , w i t h a d d i t i v e a s o p -p o s e d t o d o m i n a n t g e n e i n f l u e n c e , i n d i c a t e st h a t g e n e t i c i n f l u e n c e w a s t h e s u m o f s o m e n u m -b e r o f a p p r o x i m a t e l y e q u a l g e n e e f f e c ts . T h es p e c i fi c e n v i r o n m e n t a s p e c t o f t h e f i t te d m o d e li m p l i e s t h a t t h e e n v i r o n m e n t a l i n f l u e n c e s w e r eo f a m o r e i n d i vi d u a l , a s o p p o s e d t o a m o r ec o m m o n e n v i r o n m e n t a l , n a t u r e . T h i s i s c o n si s -t e n t w i t h t h e p r e v a i l i n g c o n c e p t t h a t m a l o c c l u -s i o n h a s a m u l t i f a c t o r i a l o r i g i n c o m b i n a t i o n o fa n u m b e r o f g e n e t ic a n d e n v i r o n m e n t a l f a c t o rs )a n d i m p l i e s t h a t s p e c if i c e n v i r o n m e n t a l t r e a t-m e n t ) f a c t o r s m i g h t h a v e s o m e e f f e c t o n t h etraits.

Anal ys i s o f t he so f t t i s sue assoc i a t ed wi t h an -t e r i o r v e rt i ca l h e i g h t , a s m e a s u r e d o n t h e f a c ia lp r o f i l e o f l a t e ra l p h o t o g r a p h s t a k e n o f 42 p a i rso f m o n o z y g o t i c t w in s a n d 3 7 p a i r s o f d i z yg o t ict wins , p ro du ce d a her i t ab i l i ty es t i mat e o f 0 .66f o r a n t e r i o r f a c e h e ig h t. ~ 5 L a t e r a l c e p h a l o g r a p h sw e r e u s e d i n a p a t h a n a l y s i s s t u d y t o c o m p a r et he he r i t ab i l i t y o f ho r i z on t a l a nd ver t i ca l d i s-t a n c e s a s o p p o s e d t o p r o p o r t i o n s o r r a ti o s ) o n5 5 p a ir s o f tw i ns o f t h e s a m e g e n d e r , r a n g i n gf r o m 1 3 t o 2 0 y e a r s o f a g e w h o h a d n o t u n d e r -g o n e o r t h o d o n t i c t r e a t m e n t . ~6 T h e m e a n a g e o ft he monozygo t i c t wi ns was 15 .2 year s , whereast he mean age fo r t he d i zygo t i c t wi ns was 14 .7y e a r s. A l t h o u g h t h e h e r i t a b i l it y e s t i m a t e f o r b o t ht h e l o w e r a n t e r i o r f a c e h e i g h t a n d t o t a l a n t e r i o rf ace he i gh t was 0 .86 , i t was marked l y l ower fo r

u p p e r a n t e r i o r f a c e h e i g h t 0 .1 6) a n d p o s t e r i o rf ace he i gh t 0 .26 ) . Th ese t wo r e l a t i ve ly l ow her -i ta b i li t y e s t im a t e s w e r e p r o b a b l y a r t i f a c ts c a u s e db y r a n d o m v a r i a t i o n i n a l i m i t e d s a m p l e . T h el i k e li h o o d o f s o m e r a n d o m v a r ia t io n , e x p r e s s e di n t h e p a t h a n a l y s i s u s e d , w a s r e i n f o r c e d w h e nm a r k e d l y h i g h e r e s t i m a t e s o f h e ri t a b i li t y f o r u p -p e r a n t e r i o r f a c e h e i g h t 0 .8 1 ) a n d p o s t e r i o rf a c e h e i g h t 0 . 88 ) w e r e d e t e r m i n e d i n t h e s a m es a m p l e b y u s in g w e i g h t e d m e a n s o f m o n o z y g o t i cand d i zygo t i c twi n es t i mat e s i n s t ead o f pa t h ana l -ysis. ~

A l t h o u g h a t t r ib u t e d t o r a n d o m e r r o r in t h ep a t h a n a ly s is m e t h o d , t h e d i c h o t o m y o f th e h e r -i ta b i li ty b e t w e e n t h e u p p e r a n t e r i o r f a c e h e i g h ta n d t h e l o w e r a n t e r i o r f a c e h e i g h t e c h o e d t h ef i n d i n g s o f a n e a r l i e r s t u d y o n 3 5 p a i rs o fmo noz ygo t i c t wi ns and 21 pa i r s o f l i ke- sex d izy -go t i c twi ns r ang i ng i n age f ro m 18-55 year s ,w i t h a m e d i a n a g e o f 24 ) i n w h i c h t h e r e w a s as i g n i fi c a n t d i f f e r e n c e i n t h e i n t r a p a i r d i f f e r e n c e s

v a r i a n c e ) b e t w e e n t h e m o n o z y g o t i c a n d d i zy -g o t i c t w i n s f o r t o t a l a n t e r i o r f a c e h e i g h t a n dl o w e r a n t e r i o r f a c e h e i g h t b u t n o t f o r u p p e ra n t e r i o r f a c e h e i g h t . T h e u p p e r a n t e r i o r f a c eh e i g h t w a s e s s e n t i a l l y t h e s a m e b e t w e e n e a c hpai r o f t wi ns , r egard l ess o f t he i r zygos i t y . I t wasc o n c l u d e d t h a t t h e d i c h o t o m y o f t h e h e r i ta b i l it yb e t w e e n t h e u p p e r a n t e r i o r f a c e h e i g h t a n d t h el o w e r a n t e r i o r f a c e h e i g h t , a l o n g w i t h t h e r e l a -t i ve l y h i gh her i t ab i l i t y o f t he t o t a l an t e r i o r f a cehe i gh t , i n f e r s t ha t i t i s t he l ower an t e r i o r f aceh e i g h t t h a t i s p r i m a r i l y r e s p o n s i b l e f o r t h e h e r -i t ab i l i t y o f t he t o t a l an t e r i o r f ace he i gh t .~s

T h e d i c h o t o m y w as a l s o s u g g e s t e d w h e n l a t-e r al c e p h a l o m e t r ic m e a s u r e m e n t s w e r e m a d e o f67 monozygo t i c t wi n pa i r s and 29 d i zygo t i c t wi np a i r s a n d i n v e s t i g a te d t h r o u g h f a c t o r a n al y si sw i t h s u b s e q u e n t e s t i m a t i o n o f he r i ta b i li t y. T h efac t o r wi t h t he l a rges t her i t ab i l i t y es t i mat e

0 .7 6 ) i n c l u d e d t h e l o w e r a n t e r i o r f a c e h e i g h ta n d t o t a l a n t e r i o r f a c e h e i g h t . T h e h e r i t a b i l i t ye s t i m a t e f o r t h e f a c t o r t h a t i n c l u d e d u p p e r a n -t e r i o r f ace he i gh t was 0 .48 , whereas t ha t fo r t o t a lp o s t e r i o r f a c e h e i g h t a n d l o w e r p o s t e r i o r f a c ehe i g h t was 0 .31 . m

I f t h e r e a r e r e l a t iv e l y h i g h c o m m o n i n h e r i -t a n c e e s t i m a t e s f o r t h e u p p e r a n t e r i o r f a c eh e i g h t a n d p o s t e r i o r fa c e h e i g h t as c o m p a r e d t ot h e l o w e r a n t e r i o r f a c e h e i g h t a n d t o t a l a n t e r i o rf a c e h e i g h t , t h i s s u g g e s t s t h a t s o m e c o m m o n

c u l t u ra l ) e n v i r o n m e n t a l f a c t o r s ) h a v e g r e a t e r


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i n f l ue nce on t hese t r a it s . 16 On e con j ec t u rem i g h t b e d i e t c o n s i s t e n c y 9 o n t h e p o s t e r i o r f a c eh e i g h t a n d t h e d e v e l o p m e n t o f n as a l a ir w a y p a -t e n c y o n t h e u p p e r a n t e r i o r f a c e h e i g h t; h o w -e v e r , t h e p r e s e n c e o f r a n d o m v a r i a t i o n m a y a ls ob e a n e x p l a n a t i o n f o r t h e s e r e l a ti v e ly h i g h c o m -m on i nhe r i t an ce es t i mat es . 16,17 In s upp or t o f t hee n v i r o n m e n t a l e f f e ct o n n a s al d e v e l o p m e n t i st h e r e j e c t i o n o f t h e n u l l h y p o t h e s i s t h a t t h e r e isn o c o m m o n s i b l in g e ff e c t o n n a s a l h e ig h t . T h e s er e s u lt s a r e b a s e d o n p a t h a n a ly s is o f f a m i l y r e -s e m b l a n c e u s i n g c r a n i o f a c i a l a n t h r o p o m e t r i cm e a s u r e m e n t s o f 1 , 7 6 3 i n d i v i d u a l s i n 3 9 9 f a m i -l ie s f r o m a r u r a l c o m m u n i t y i n A n d h r a P r a d e s h ,Ind ia. 21

C o n s i d e r i n g t h e e f f e c t o f b r e a t h i n g o n t h ev e r t ic a l d i m e n s i o n , t h e m o s t s tr i k i ng d i f f e r e n c ew as f o u n d i n a c o m p a r i s o n o f c e p h a l o m e t r i cf a c i a l d i m e n s i o n s i n 2 5 w h i t e c h i l d r e n w i t h p e -r e n n i a l a l l e r g i c r h i n i t i s . T h e s e a p p a r e n t m o u t hb r e a t h e r s w e r e c o m p a r e d w i t h t h e i r 2 5 s i b l i n g sw h o a p p a r e n t l y w e r e n o t m o u t h b r e a t h e r s a n dd i d n o t h a v e p e r e n n i a l a l l e r g i c r h i n i t i s a n d 1 4n a s a l b r e a t h i n g c o n t r o l s u b j e c t s . T h e a n a l y s i sr e v e a l e d t h a t t h e a l l e r g i c c h i l d r e n h a d a m o r ed i ve rgen t f ac i a l pa t t e rn . 22 Th i s i s cons i s t en t wi t ht he f i nd i ngs i n a s t udy o f 100 l l -year -o l d F i nn i shc h i l d r e n i n w h i c h t h e r e w a s a n i n c r e a s e i n t h ev e r ti c a l d i m e n s i o n i n m o d e r a t e a n d s e v e r e ly a l-l e rg i c sub j ec t s . 23 An add i t i on a l r ep o r t wi t h s i m-i l a r f i nd i ngs was based on a s t udy o f 37 ch i l d renwi t h pere nn i a l a l l e rg i c rh i n i t is ( ages 5 -10 year s )a n d m a t c h e d c o n t r o l s . 24

I f a n i n c r e a s e i n t o ta l a n t e r i o r f a c e h e i g h t a n dl o w e r a n t e r i o r f a c e h e i g h t , i n p a r t i c u l a r , a r e a s -s o c i a t e d w i t h p e r e n n i a l a l l e r g i c r h i n i t i s a n dm o u t h b r e a t h i n g , w h y d o s o m e ( a l t h o u g h n o ta l l ) s t ud i es i nd i ca t e a d i cho t omy i n t he es t i mat eso f h e r i t a b il i t y o f th e u p p e r a n t e r i o r f a c e h e i g h ta n d t h e l o w e r p o s t e r i o r f a c e h e i g h t ? O n e h y -p o t h e s i s i s t h a t t h e l o w e r a n t e r i o r f a c e h e i g h tm a y h a v e a r e l a ti v e ly g r e a t e r h e r i t a bi l i ty t h a n t h eu p p e r a n t e r i o r f a c e h e i g h t i n s o m e i n d i v i d u a l su n l e s s i n c r e a s e d n a s a l o b s t r u c t i o n , r e s u l t i n g i nm o u t h b r e a t h i n g , b e c o m e s a p r e d o m i n a t i n g f a c -t o r . Agai n , her i t ab i l i t y i s a descr i p t i ve s t a ti s ti c fo ra p a r t i c u l a r s a m p l e u n d e r d e f i n e d e n v i r o n m e n -t a l cond i t i ons .

S t u d ie s t h a t e s t i m a t e h e r i t a b il i t y o f c r a n i o fa -c ia l s t r u c tu r e s m a y h a v e a b ia s b e c a u s e t h e y h a v eg e n e r a ll y b e e n p e r f o r m e d w i t h s ub j ec t s w h o h a dn o t u n d e r g o n e o r t h o d o n t i c t r e a t m e n t ; t h u s,

s u b j e c t s w i t h a n e x t r e m e m a l o c c l u s i o n t e n d t ob e e x c l u d e d . 25 I n a t h o u g h t - p r o v o k i n g s t u d y o ft h e h e r i t a b i li t y o f c e p h a l o m e t r i c a n d o c c l u sa lvar i ab l es i n s i b l i ngs wi t h over t mal occ l us i ons , i twas fou nd t ha t , i n con t r a s t t o a se ri es o f s imi l a rs u b j e c t s w i t h n a t u r a l l y o c c u r r i n g g o o d o c c l u -s i on , t he her i t ab i l i t y es t i mat es fo r c r an i o fac i a lske l e t a l var i ab l es i n t he sub j ec t s wi t h over t mal -occ l us i ons were s i gn i f i can t l y l ower , and t he her -i t ab i li t y es t i ma t es fo r occ l usa l va r i a t i ons were s ig -n i f i can t l y h i gher25 To quo t e Ki ng e t a l , 25 Wep r o p o s e t h a t t h e s u b s ta n t i v e m e a s u r e s o f i n t e r s i bs i mi l a r i t y fo r occ l usa l t r a i t s r e f l ec t s i mi l a r r e -s p o n s e s t o e n v i r o n m e n t a l f a c t o r s c o m m o n t obo t h s i b l i ngs . Tha t i s , g i ven gene t i ca l l y i n f l u -e n c e d f a c i a l t y p e s a n d g r o w t h p a t t e r n s , s i b l i n g sa r e l ik e ly t o r e s p o n d t o e n v i r o n m e n t a l f a c t o r s( e g, r e d u c e d m a s t i c a t o r y s tr e ss , c h r o n i c m o u t h -b r e a t h i n g ) i n s i m i l a r f a s h i o ns . M a l o c c l u s i o n sa p p e a r t o b e a c q u i r e d , b u t t h e f u n d a m e n t a l g e -n e t i c c o n t r o l o f c r a n i o f a c ia l f o r m p r e d i s p o s e ss i b l i n g s i n t o c o m p a r a b l e p h y s i o l o g i c r e s p o n s e s ,t h a t o f t e n l e a d t o d e v e l o p m e n t o f s im i l a r m a l o c -clus ions . 25

Does Knowing The Heritabi l i ty MatterIn TreatmentI t has been s t a t ed t ha t , Var i ab l es wi t h a l owerg e n e t i c d e t e r m i n a t i o n a r e m o r e o p e n t o i n fl u -e n c e b y , f o r e x a m p l e , o r t h o p e d i c c o r r e c t i o nt h a n a r e v a r ia b l e s w i t h a h i g h g e n e t i c d e t e r m i -n a t i o n , w h i c h a r e n o t s o e as i ly c h a n g e d b y t h ee n v i r o n m e n t . 14 T h i s i m p l ie s t h a t t h e g e n e t i ci n f l u e n c e i s a p r e d e t e r m i n i n g , u n a l t e r a b l e f a c-t o r . However , as has a l r eady been d i scussed , i tm a y b e a l t e r e d u n d e r d i f fe r e n t e n v i r o n m e n t a l( t r e a t m e n t ) c o n d i t i o n s . C e r ta i n ly , t r e a t m e n t d e -p e n d s o n t h e o r i g i n o f a d i s o r d e r i f t h a t c a u s e i sk n o w n a n d s p e c if i c. H o w e v e r , i t ha s a l s o b e e np o i n t e d o u t t h a t c o n t ra r y t o p o p u l a r o p i n i o n t h ee x t e n t t h a t a p a r t i c u l a r t r a i t i s i n f l u e n c e d ( o r ify o u w is h e v e n d e t e r m i n e d ) b y g e n e t i c f a c t o r sma y have l i tt l e i f any e f f ec t on t he success o fe n v i r o n m e n t a l ( t r e a t m e n t ) i n t e rv e n t io n . % W h a tis i m p o r t a n t is th e r e s p o n s e o f t h e i n d i v i d u a l t ot h e e n v i r o n m e n t a l ( t r e a t m e n t ) i n t e r v e n t i o n ,w h i c h m a y b e s i m i l ar f o r c o m p a r a b l e g e n o t y p e s( o r a t l e a s t t h e g e n e s t h a t a r e g o i n g t o i n f l u e n c et h e r e s p o n s e t o t h e p a r t i c u l a r i n t e r v e n t i o n ) . G e -ne t i c f ac t o r s t ha t i n f l uence a t r a i t may a l so i n -f l u e n c e t h e r e s p o n s e t o i n t e r v e n t i o n d e s i g n e d t o


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Development of the Vertical Dimension 117

alter that trait, but that is not inherently knownin the estima tion of the heritability of a trait.The question is, depen din g on the ability of theindividual to respond to a given environment(treatment), will the interaction of the new oraltered environment, with the genetic factorspresent, result in a change in the phenotype?

Nature Nurture or Both?It has been stated that analyses of craniofacialstructures have led to the conclusion that theyhave moderate to high estimated heritabilitiesand that they are primarily a consequence ofnat ure rath er than nurtu reY 5 In a sense, this istrue for what estimates of the heritability repre-sent, but it is often interpreted that genetic fac-tors are influencing development inde pendentlyof the envi ronm ent and that genetic factors havecontrolled or determined the development. Thebasic interpreta tion of the estimation of herita-bility is that the genetic and environmental fac-tors are separate, thus they can be port ione d anddo not interact. This has been typified by thephrase nature versus nurture, which by its veryconstruction defines a separation and even op-position.

To say, for example, based on heritability es-timates of a particular sample that the anteriorface height is 70 genetic and 30 environ-mental gives a misleading dichotomy betweengenetic and environmental factors and obscuresthe fact that most if not all huma n disease (anddevelopment) results from the interaction be-tween genetic susceptibility and environmental-moderat ing fac tor s 27 This is true even for con-ditions in which an environmental influence isknown to be strong, such as in smoking andoropharyngeal cancer. Everyone who smokesdoes not develop cancer, which indicates an in-teraction of smoking with other factors, includ-ing g ene tic susceptibility. 9s Essentially all aspect sof normal and abnormal developmen t are insome way the result of the interaction of geneticand environmental factors; thus, there is nocompel ling reason to label a trait or cond ition asbeing either genetic or environmenta l. 97

Searching For Genet ic FactorsHeritability estimates can indicate the relativecontribution or influence that genetic factors

have had on a trait, which is a consideration withrega rd to the feasibility of a search for identify-ing those factors. The search for DNA markerslinked with certain phenotypes may indicate ar-eas of the ge nom e that have a gene or genes thatinfluence the phenotype; however, this processdoes not necessarily precisely define what genein the area is contributing or what allele of thatgene may be more influential than others. How-ever, the search for markers linked with certainphenotypes can indicate areas of the geno methat contain influential genes that were previ-ously not known or even suspected to have aninfluence on the phenotype. Once a particulargene or genes in an area of the ge nome areidentified, they bec ome c andidate genes for spe-cific analysis of their structure to pinpoint thereleva nt allele (s).

Study of the influence of particular geneticfactors on development may be performed byusing a candidate gene chosen for the functionof its associated protei n. A n exam ple is a study ofthe association of the Pro56 1Th r (P56IT) vari-ant in the growth hormone receptor geneGHR), which is considered to be an important

factor in craniofacial and skeletal growth. Out ofa normal Japan ese sample of 50 men a nd 50women, those who did not have the GHR P56ITallele had a significantly greater mandi bula r ra-mus length (condylion-gonion) than did thosewith the GHR PB6IT allele. The average mandib-ular ramus height, in those with the GHR P56ITallele, was 4.65 mm shorter than the average forthose without the GHR P56IT allele. This signif-icant correlation between the GHR P56IT alleleand shorter mandibular ramus height was con-firmed in an additional 80 women29

Interestingly, the association was with themandibular ramus height but not mandibularbody length, maxillary length, or anterior cra-nial base length. These data suggest an effectthat is site, area, or region specific. Although itwas concluded that the GHR P56IT allele may beassociated with decreased growth of mandi bula rheight and can be a genetic marker for it, it isnot clear if the effect is directly on the ma ndibleand/or on another nearby t issue or matrix. I twould also be interesting to see what effect dif-ferent diet consistencies have on individuals withand without the GHR P56IT allele, as a way oflooking at genetic and environmental interac-tion.


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11 8 James K. Hartsfield l

S u m m a r y a n d C o n c l u s i o nThe relevance of analyzing the dev elop ment ofthe vertical dimension to clinical practice is firstto determine if there is a vertical dimensioncomp onen t to the malocclusion and then ascer-tain what factors are having the greatest influ-ence on the vertical dimension problem in thatindividual. Unfortunately, at this time, studieson the genetic and environmental factors thatinfluence the d evelo pmen t of vertical dimens ionare representative of the samples studied andnot necessarily of any particular individual. Inaddition, the extent that a particular trait is in-fluence d by genetic factors may have little if anyeffect on success of environmental (treatment)intervention. It may be that genetic factors thatinfluenced a trait will also influence the re-sponse to intervention to alter that trait, or othergenetic factors may be involved in the response.Ther efor e, the possibility for altering the envi-ronment to gain a more favorable dimension istheoretically possible, even in individuals inwhich the vertical dimension does have a rela-tively high genetic influence. However, the ques-tion of how environm ental and genetic factorsinteract (a question that essentially cannot beanswe red in estimates of heritability) is mos trelevant to clinical practice because it may ex-plain why a particular alteration of the environ-ment ( treatment) in one compliant patient maybe successful and n ot in ano ther. Study of theseenvironmental and genetic factors has been dif-ficult at the clinical level because of the relativelysmall sample sizes and lack of marker s to analyzegenetic diversity from one patient to the next.

Animal studies using inbred strains comparethe different responses of an environme ntal fac-tor against consistent genotypes and the effect ofdifferent background genotypes on the pheno-typic exp res sio n of a specific ge ne mut ati on. 3, e ~Although mice, the most commo nly used mam-malian species for genetic inbred strain studies,have been used and will continue to be used forthe study of genes that cause disease a nd aber-rations in mammalian development, their differ-ent craniofacial morphology (ie, the presence ofsnouts and single dentition with incisors andmolars only) may not be readily applicable tosome of the clinical questions ortho dontists haveregarding craniofacial growth in humans. Stud-ies using ma ting crosses of various inbr ed strains

of mice help estimate the n umb er of genes thatinfluence a phenotype. The development of themouse genome project, not far behind the hu-man genome project, will increase the numberof known DNA markers that may be used in thestudy of putative relevant genetic factors andgenetic-environmental interactions, which maythen be tested for in the human population.

The human genome project resulted in notonly a single huma n g eno me sequen ce com-posed of overlapping parts from many humansbut also cataloge d som e 1.4 million sites of vari-ation in the human genome sequence. Thisincreased n umb er of variations (or polymor-phisms) may be used as markers to perfor mgenetic (including genetic-environment interac-tion) analysis in an outbred population such ashuman beings. Our genome varies from oneindividual to the next, most often in terms ofsingle-base changes of the DNA called single-nucleotide polymorphisms. The main use of thishuman single-nucleotide polymorphism mapwill be to deter mine the contrib utions of genesto diseases (or nondisease phenotypes) thathave a complex, nmltifactorial basis. Althoughthe scale of such studies could be dau nting andthere are still problems to solve, the potential forstudying how natural variation leads to each on eof our qualities is significant. This appr oa ch ma ybe the best opportun ity yet to better under stan dthe roles of nature and nu rture rather tha n na-ture versus nurt ure in dev elop ment . 32

c k n o w l e d g m e n tT h e a u t h o r t h a n k s D r W . E u g e n e R o b e r t s f o r r e v ie w i n g th em a n u s c r i p t a n d M s . R o b y n T i b b s, M s . M a d e l i n e H a w k i n s ,a n d M s . C l a u d e t te M a u r e r f o r r e t r i e v i n g a n d c o p y i n g r e f e r-e n c e s .

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4 . E s c o b a r V , B i x l e r D : O 1 t h e c l a s s i f i c a t i o n o f t h e a c r o -c e p h a l o s y n d a c t y l y s y n d r o m e s . C l i n G e n e t 1 2 : 16 9 - 17 8 ,1 9 7 7

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26. Smit h RJ, Balit HL: Problems and m etho ds in researchon the genetics of dental occlusion. Angle Orthod 47:65-77, 197727, Khoury MJ, ThrasherJF, Burke W, et al: Challenges incommunicating genetics: A public health approach.Genet Med 2:198-202, 2000

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vertical dimension 2

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