O nanismo acondroplásico: aspectos estruturais e genéticos.
Autor: Gladis Franck | Publicado: 2015-08-16T23:59:00-03:00

por Gladis Franck da Cunha

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<![endif]-->Peter
Dinklage, ator que dá vida ao personagem Tyrion Lannister de Game of Thrones<!--[if gte mso 9]>
 
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A
acondroplasia é uma doença que provoca um
crescimento ósseo desproporcional que leva ao nanismo .
Este distúrbio ocorre em aproximadamente
um em cada 25 mil nascidos vivos, de acordo com o Hospital
Infantil de Filadélfia (CHOP),
sendo mais comum em homens do que em
mulheres.



O nanismo é definido como uma
condição de baixa estatura
em um adulto, em média sua altura não ultrapassa 130 cm, mas a
altura máxima dos homens com acondroplasia pode chegar a 150 cm e
nas mulheres adultas gira em torno de 140 cm.



&nbsp;As pessoas com acondroplasia não têm apenas pequena estatura,
mas uma relação desproporcional com um torso de tamanho normal e membros
curtos. Esta anomalia genética é o tipo mais comum de nanismo desproporcional.

Aspectos estruturais da
acondroplasia.



As
características morfológicas mais comuns incluem:

1-
baixa estatura (significativamente abaixo da média para a idade e sexo);
&nbsp;

2- braços e pernas curtas (especialmente os braços e coxas) em comparação
com a altura do tronco; 



3-
&nbsp;os dedos são curtos (so dedos anelar e médio também podem ser afastados um do outro);&nbsp;

4- a&nbsp; cabeça é desproporcionalmente grande em relação ao corpo, destacando-se a testa &nbsp;anormalmente grande;&nbsp;

5- a região central da face (entre
a testa e maxilar
superior) é pouco desenvolvida.

&nbsp;

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<![endif]-->O ator
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&nbsp;Além disso, Crianças e adultos com acondroplasia podem
apresentar outros sintomas como:



1-
&nbsp;dificuldade em dobrar os cotovelos;



2-
tendência a &nbsp;obesidade; 



3-
&nbsp;infecções de ouvido recorrentes, por causa
do estreitaento de canais ósseos; 



4-
&nbsp;pernas arqueadas; 



5-
uma &nbsp;curvatura anormal da coluna (cifose
ou lordose).



6- &nbsp;desenvolver estenose espinhal, que se
caracteriza por um estreitamento do canal espinhal, que pode comprimir a medula nervosa. 



7- há também um risco maior de
desenvolvimento de doenças cardíacas.






<!--[if gte mso 9]>
 
  
 
<![endif]-->Hervé
Villechaize viveu o personagem Tatoo de Ilha da Fantasia<!--[if gte mso 9]>
 
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Os problemas de saúde de um
bebê
acondroplásico podem incluir:

&nbsp;
1- a&nbsp; diminuição do tônus muscular, o que pode causar atrasos na caminhada e outras habilidades motoras.



2-
presença de &nbsp;apneia e hidrocefalia.



3-
&nbsp;estenose da coluna vertebral.



Tais complicações aumentam o risco de morte no primeiro ano de vida. 




<!--[if gte mso 9]>
 
  
 
<![endif]-->Os
atores Meredith Eaton (Boston Legal) e Martin Klebba (Piratas do Caribe)<!--[if gte mso 9]>
 
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O que é a acondroplasia?

Durante o desenvolvimento fetal precoce, a maior parte do esqueleto é constituída por cartilagem, cujo termo original
deriva do grego &nbsp;khondr(o), à
medida que o feto se desenvolve a maior parte da cartilagem vai sendo substituída pelo
tecido ósseo. Este processo continua durante todo o período de
crescimento, até que todo tecido cartilaginoso do esqueleto seja convertido a
osso, restando apenas a cartilagem articular que reveste as extremidades dos
ossos ou epífises. 



O tecido ósseo não “cresce” por si mesmo, o
que cresce é o tecido cartilaginoso, assim enquanto houver crescimento das
cartilagens nosso esqueleto cresce, mas assim que cessa a formação de
cartilagem e ela é substituída por tecido ósseo cessa o crescimento.

&nbsp;

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<![endif]-->Kenny
Baker deu vida ao simpático robô R2-D2 da série Star Wars<!--[if gte mso 9]>
 
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A palavra acondroplasia contém o prefixo “a”
que significa negação e ainda o sufixo plasia, que também deriva do grego e
significa “formação celular”. Assim, este termo designa uma anomalia que
resulta da falta de síntese de cartilagens e de sua consequente conversão em
tecido ósseo.



Geneticamente,
esta condição é causada por mutações no gene FGFR3 (do inglês fibroblast growth
factor receptor). Duas mutações deletérias neste gene (G1138A e G1138C) estão relacionadas à gênese da
acondroplasia. Este gene codifica um receptor celular para um fator de
crescimento, que tem função primordial no controle da maturação da cartilagem óssea e, consequentemente, participa
ativamente da modulação do crescimento ósseo. 



Em
outras palavras, o gene FGFR3 instrui o organismo a produzir uma proteína necessária
para o crescimento de e a manutenção dos
ossos. Desta forma, mutações neste gene resultam em função anômala do receptor
por ele codificado. A consequência clínica é a formação de ossos mais curtos e
de formato anormal.



A genética da acondroplasia



O gene FGFR3 está
localizado em cromossomos autossômicos e é dominante, pois basta a presença de
um alelo com a mutação para o portador manifestar o nanismo. Melhor dizendo, os
portadores sempre têm apenas um alelo defeituoso, pois quando são herdados os
dois alelos, condição denominada acondroplasia homozigota, os efeitos são tão
deletérios que inviabilizam o portador.&nbsp;



Crianças com esta condição são
geralmente natimortas ou morrem poucos meses após o nascimento. Esta condição,
dificilmente ocorre se um dos progenitores não for anão, em geral, somente os
filhos de casamento entre anões pode gerar filhos com acondroplasia homozigota.



Apesar de ser uma
característica dominante,de acordo com o National
Human Genome Research Institute (NHGRI) &nbsp;mais de 80% dos anões acondroplásicos são
filhos de pais normais e o nanismo, nestes casos, é causado por mutações
espontâneas do gene FGFR3 nos gametas de um dos progenitores.



Assim sendo,
somente 20% dos casos são devidos a herança genética, ou seja, quando um dos
progenitores é anão. Nestes casos, a probabilidade de nascer um filho ou filha
com acondroplasia é de 50%.
&nbsp;

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<![endif]-->O
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Por
outro lado, quando ambos os pais são anões há uma probabilidade de 25% de
nascer uma criança normal, bem como 25% de chances de nascer um portador da
acondroplasia homozigota.



Efeitos da idade paterna no surgimento do
nanismo acondroplásico.



Os
casos esporádicos de acondroplasia, em que pai e mãe são normais
e apenas os filhos ou filhas são afetados têm sido
associados com idade paterna avançada, sugerindo que estas mutações ocorrem preferencialmente
durante a espermatogênese. 



No
estudo de Wilkin e colaboradores (1998) em que foram analisadas noventa e nove famílias, cada um com um
caso esporádico de acondroplasia
em uma criança,&nbsp; a mutação para acondroplasia foi detectada, de forma inequívoca, &nbsp;no cromossomo de origem
paterna em &nbsp;40 casos. 



Este
achado é consistente com a observação clínica de que a idade avançada do pai favorece o surgimento de novos casos de acondroplasia
e sugere que os
fatores que influenciam a
replicação ou o reparo do DNA
durante a espermatogênese pode predispor
para a ocorrência as mutações G1138A e C do FGFR3.
O mesmo não foi observado para a ovogênese.

Referências e links







1-Minha Vida (site) Acondroplasia. s/d. Disponível em: http://www.minhavida.com.br/saude/temas/acondroplasia,
acesso em 16/08/2015



2- Rose Kivi. Achondroplasia; Medically Reviewed by Brenda B.
Spriggs, MD, MPH, FACP on June 23, 2012. Disponível em: http://www.healthline.com/health/achondroplasia#Overview1




3- Douglas J. Wilkin; &nbsp;Jinny K. Szabo; Rhoda Cameron; &nbsp;Shirley Henderson; &nbsp;Gary A. Bellus; Michelle L. Mack; Ilkka
Kaitila; &nbsp;John Loughlin; &nbsp;Arnold Munnich; Bryan Sykes; &nbsp;Jacky Bonaventure; &nbsp;Clair A. Francomano. Mutations in Fibroblast Growth-Factor Receptor 3 in Sporadic Cases of
Achondroplasia Occur Exclusively on the Paternally Derived Chromosome. The American Journal of Human Genetics, Volume
63, Issue 3, p711–716, September 1998, disponível em: http://www.sciencedirect.com/science/article/pii/S000292970761372X&nbsp;