Clinica de las

anormalidades
Geneticas
Dr Gabriel Silva Arevalo
Pediatra-Genetista.
CIB-Patologia

Mutaciones

C
T
G
G
A
C
T
CCTGATGGATCGCGTACGTTGTACGCACAGTGTCGAAAAAG
CATACGGGGACTGCACGTACACGTAGCACGGCGTCGATTTT
GACGTGCACGTGTCAGTGCGATGAGTGAGTGACACACAGTG
CAGCGTGTGTACCCATGCGCGAAGTATGT

An important mechanism that is now well established for many repeat expansion diseases is the toxicity of RNAs
that contain expanded repeat sequences. In these diseases, the RNAs that contain expanded repeats interact with different RNA-binding proteins
(coloured shapes) to produce disease. This is a 'trans-dominant' model of RNA toxicity: the interaction of mutant RNA
with RNA-binding proteins is envisioned to interfere with the functions of the interacting proteins,
which leads to abnormalities in the pathways regulated by the RNA-binding proteins

Creacion

CLASES DE HERENCIA MENDELIANA:

HERENCIA DOMINANTE

Sindrome de Marfan

Expression y Penetrance

HERENCIA MENDELIANA RECESIVA

UCD
Via Bioquimica

Datos Clinicos
6q23 Arg1.
Role en asma y
metabolismo de NO.

Leve a moderada NH4,

progresiva
espasticidad,convulsiones
y fallo en el desarrollo
intelectual debido al alto
nivel de CGG.

CGG alto, NH4 L-M.

Efectos de Argininasa

Riesgos de transmision de
enfermedad ligada a X

Anormalidades
Cromosomicas

13

R e tr a s o m e n ta l li g e r o

12
1 1 ,2
1 1 ,1
1 1 ,1
1 1 ,2

40

2 1 ,1

30

2 1 ,2
2 1 ,3

20

2 2 ,1
2 2 ,2
2 2 ,3

M ic ro c e fa lia
L e u c e m ia
Im p la n ta c i n b a ja d e o re ja s
E s te n o s is d u o d e n a l
R e tr a s o m e n ta l p r o f u n d o
C a rd io p a ta

10
P li e g u e s e p ic n tic o s
P r o tr u s i n d e la le n g u a
C li n o d a c til ia d e l m e i q u e
I n te r v a l o e n tr e 1 er y 2 d e d o s d e l p i e

T e le c a n to
F isu ra s p a lp e b ra le s o b lic u a s
D e r m a to g lif o s
M a n o s c o r ta s y a n c h a s

M a n c h a s d e B r u s h f ie ld

F ig u r a 1 . J o h n L a n g d o n H . D o w n .

F ig u r a 2 . C o r r e la c i n e n tr e f e n o tip o y c ito g e n tic a ( c o n p e r m i s o d e J o h n W ill e y S o n s , L t d .) .

b a s o s p e c h a d o q u e e l s n d ro m e d e D o w n te n a a lg n v n c u lo
g e n tic o . C o m e n z e s tu d ia n d o la s h u e lla s d a c tila re s e im p ro n ta s p a lm a re s d e e s to s p a c ie n te s y la s c o m p a r c o n la s d e n i o s
n o a fe c ta d o s . L e je u n e p u d o p re c is a r q u e la s h u e lla s e ra n p e c u lia re s e n e s to s p a c ie n te s y s o s p e c h q u e , a l te n e r u n o rig e n m u y
p re c o z e n e l d e s a rro llo y p re s e n ta r u n o s c a m b io s ta n c o n s id e ra b le s , p r o b a b le m e n te e llo s e d e b a a la a c c i n d e m u c h o s g e n e s
lo c a liz a d o s e n u n c r o m o s o m a . E n 1 9 5 7 p u d o e s tu d ia r e l c a rio tip o d e n u e v e n i o s a fe c to s d e l s n d ro m e d e D o w n , c o m p r o b a n d o
q u e te n a n 4 7 c r o m o s o m a s ; e n e l a o 1 9 5 9 e s ta b le c i q u e e l s n d ro m e d e D o w n e s ta b a o rig in a d o p o r la p re s e n c ia d e u n c ro m o s o m a s u p e r n u m e r a r io , id e n ti f ic a d o c o m o 2 1 (1 2 ).
H a s ta la c o m p ro b a c i n c ito g e n tic a c a ra c te rs tic a d e l s n d ro m e d e D o w n , lo s c o n o c im ie n to s s o b re e s ta fre c u e n te a n o m a la q u e c u r s a c o n d is c a p a c id a d in te le c tu a l, a lte r a c io n e s e n
e l f e n o tip o y f r e c u e n te c a r d io p a ta c o n g n ita , e r a n e x c lu s iv a -

d e la s c u a le s e s tris m ic a 2 1 ) y la s tra s lo c a c io n e s , r o b e rts o n ia n a s o n o . C o n n o ta b le d ife re n c ia , la tr is o m a 2 1 re g u la r d e o r ig e n m a te rn o e s e l c a rio tip o m s fre c u e n te e n lo s a fe c ta d o s (9 5 % );

s e g u i d a d e l a s t r a s l o c a c i o n e s ( 4 % ) y d e l o s m o s a i c i s m o s ( 1 % ) (1 6 ).
E l s n d r o m e d e D o w n p r e s e n ta u n a f r e c u e n c ia d e l 0 ,5 % d e
t o d a s l a s c o n c e p c i o n e s y d e 1 : 8 0 0 r e c i n n a c i d o s v i v o s (1 7 ).
A p ro x im a d a m e n te 3 /4 p a rte s d e to d a s la s c o n c e p c io n e s tris m ic a s s e p ie r d e n p o r a b o r to e s p o n t n e o . A c tu a lm e n te , e l 5 0 %
d e p a c ie n te s c o n s n d ro m e d e D o w n s u p e ra n lo s 5 0 a o s y u n o
d e c a d a s ie te a lc a n z a lo s 6 8 a o s d e e d a d . L a s e n ilid a d p re m a tu ra , a s o c ia d a c o n h a lla z g o s n e u ro p a to l g ic o s q u e re c u e r d a n a
lo s d e la e n fe rm e d a d d e A lz h e im e r, a p a re c e v a ria s d c a d a s a n te s q u e e n la e d a d h a b itu a l d e in ic io d e e s ta d e m e n c ia e n la p o b la c i n g e n e ra l. L o s p a c ie n te s c o n m e n o re s p o s ib ilid a d e s d e s u p e rv iv e n c ia s o n a q u e llo s q u e p re s e n ta n c a rd io p a ta c o n g n ita ,
lo q u e ju s tific a q u e e l 2 5 % d e lo s n a c id o s v iv o s fa lle z c a n a n te s

Casos Clinicos