ESPECTRO NEUROPSIQUIATRICO Y

NEUROGENOMICO DEL SNDROME DE

RETT EN NIOS MEXICANOS

 IDENTIFICAR LAS CARACTERSTICAS CLNICAS DEL SNDROME DE RETT

MEDIANTE CLINIMETRIA NEUROPSIQUIATRICA EN UNA MUESTRA DE
NIOS MEXICANOS ATENDIDOS EN UN CENTRO DE TERCER NIVEL
REALIZAR LAS PRUEBAS GENTICAS AL PACIENTE Y ASCENDIENTES PARA
CONOCER LAS ALTERACIONES GENETICAS IMPLICADAS EN NUESTRO
MEDIO CORRELACIONAR LA EVALUACIN CLINIMETRICA
NEUROPSIQUIATRICA CON LAS ALTERACIONES GENETICAS EN NUESTRA
POBLACIN PEDITRICA AS COMO APLICAR LOS ANLISIS ESTADSTICOS
DE ANLISIS FACTORIAL Y MODELOS ACTUARIALES PERTINENTES
ESTABLECER LOS FENOTIPOS NEUROPSIQUIATRICOS DEL SNDROME
IDENTIFICABLES EN LA CLINICA Y LAS CATEGORAS SINDROMICAS DEL
ESPECTRO DIFERENCIADO DE ALTERACIN EN EL NEUROSDESARROLLO
APORTAR EVIDENCIA CIENTFICA DE ALTO NIVEL PARA SUSTENTAR EL
DIAGNOSTICO CLNICO NEUROPSIQUITRICO EN NIOS MEXICANOS CON
EL PADECIMIENTO QUE ORIENTE LAS INTERVENCIONES
FARMACOGENOMICAS EMERGENTES Y SUSTENTE LA INVESTIGACIN EN
MODELOS ANIMALES SOBRE FRMACOS CON POTENCIAL TERAPUTICO.

 The aim of this study is

to estimate the
incidence of MECP2
mutations in 32 female
Egyptian
patients clinically
diagnosed with Rett
syndrome, and to
correlate their clinical
features with
MECP2 mutation
status.

 1 in every 10,000
15,000 females worldwide.1
This protein functions by selectively
binding methyl C-pG islands in the
mammalian genome and regulates gene
expression, mainly in a repressive
manner
MECP2 has a role in maintaining
synapses between the neurons, allowing
cell-to-cell communications to take
place. The MECP2 protein also
participates in processing messenger
RNA (mRNA), which serves as genetic
blueprints for making proteins. MECP2
controls a process known as alternative
splicing, which controls the production of
different versions of certain proteins.
This process is crucial for normal
communication between neurons in the
brain.

 MECP2 is a member of a family

of nuclear protein and is
characterized by the presence
of a methyl C-pG binding
domain (MBD). These proteins
are capable of binding
specifically to methylated DNA.
Methylation is a major
modification of the eukaryotic
genome essential for the
process of mammalian
development. Binding of MECP2
gene to the methylated genepromoter DNA of certain genes
results in transcriptional
repression of these genes.5

 transcriptional repression of these

genes.5
Mutations in MECP2 may be sporadic
or germ line mutations. Alternatively,
Rett syndrome may be caused by
mutations in CDKL5 or FOXG1 genes
in 10% of cases. Sporadic cases
constitute up to 95% of cases with
MECP2 mutations. The parents in this
situation are genotypically normal
and the mutated MECP2 is usually
thought to be derived from the
normal male copy of the X
chromosome. However, the reason
behind the sperm to mutate is not yet
fully known. On the other hand, germ
line mutations are inherited from
phenotypical normal females, to her
offspring.6

 Registro de trabajos en lnea

Los resmenes de los trabajos que participarn en la XVIII Jornada de Investigacin 2017, se recibirn va
electrnica a travs del Sistema de Registro Electrnico de la Divisin de Estudios de Posgrado en la
direccin: www.sidep.fmposgrado.unam.mx
a partir del 14 de noviembre de 2016 y hasta el 06 de enero de 2017.
Los resmenes sern enviados a una evaluacin por pares y se premiaran a los mejores trabajos de
investigacin durante la Jornada de Investigacin.
El trabajo en extenso debe tener el rigor cientfico necesario y el resumen debe contener las siguientes
apartados:
a) Mximo tres cuartillas
b) No deber contener grficos ni tablas
c) Se debe anexar el trabajo en extenso en formato PDF
En caso de problemas relacionados con los resmenes para la Jornada Anual de Investigacin por favor de
ponerse en contacto con la Coordinacin de Cursos de Alta Especialidad en Medicina a la siguiente direccin
de correo electrnico: jornadadeinvestigacion@fmposgrado.unam.mx

 CMCT was shorter, but

we found elevated
CMT and shorter CSP,
which suggests
decreased excitatory
and inhibitory motor
cortical function. The
outcome was
independent
of AntuiepilepticosAED
and the presence or
absence of the MECP2
Krajnc N, Zidar J. The role of transcranial magnetic stimulation in evaluation of motor cortex excitability
mutation.
in Rett Syndrome. European journal of p a e d i a t r i c neurology 2 0 ( 2 0 1 6 ) 5 9 7 e6 0 3

Hisham Megahed a,*, Amina Hindawy

b, Mohamed Mohamady. Correlation
between clinical features and MECP2
gene mutations in patients with Rett
syndrome. Egyptian Pediatric
Association Gazette (2015) 63, 2531

 The methylCpGbinding
protein 2 gene
(MECP2) mutation can
be found in
about 90% of typical
forms of the disease,
but only in 50e70%
of atypical (variant)
cases.2

 Seizures occur in
60e80% of RTT
patients, usually in
stage II or III.4,5 There
are no specific
recommendations
for antiepileptic drug
(AED) treatment in
RTT.6,7

synaptic input.8
Transcranial magnetic stimulation (TMS) is increasingly
used in the paediatric population as it is non-invasive and
carries minimal risk. It has been used to study motor pathway
maturation and to demonstrate neurophysiological abnormalities
in neurological disorders, especially those that influence
the integrity of the corticospinal tract and cortical
excitability.9,10
The volley of excitation caused by TMS travels along the
corticospinal tract and peripheral motor neuron resulting in
muscle responses that can be recorded as motor evoked potentials
(MEP).
The cortical motor threshold (CMT) reflects the excitability
of the corticomotor projection. It is determined with the target
muscle completely relaxed (resting motor threshold, RMT) or
during slight tonic contraction of the target muscle (active
motor threshold, AMT). The cortical silent period (CSP) is a
period of disrupted voluntary tonic muscle activity after TMS
is performed. It is a measure of motor cortical inhibition. The
central motor conduction time (CMCT) is obtained by subtracting
the peripheral nerve component from the total latency
obtained by TMS.11
Short CMCT has been reported in TMS studies performed in
RTT as a unique change not observed in any other neurological
disorder. The first TMS study in RTT, performed in eight
patients in 1990, reported an abnormally low threshold for
motor cortical excitation and short latencies of MEP.12 Two
studies performed in 1996 and 1997 by the same author
confirmed the previous finding of shorter CMCT in three and
31 patients, respectively.13,14 Another study showed the
shorter latency of MEP and shorter CMCT in three patients and
a higher threshold for cortical excitation in one of these.15 The
study of six RTT patients in 1998 confirmed the shorter CMCT
and, in addition, shorter duration of the CSP.16
The shorter CMCT was attributed to hyperexcitability of
cortical neurons and/or spinal motor neurons, but was not
studied further.
The diagnosis of RTT in these studies was established according
to clinical criteria as genetic testing of MECP2 was not
available at that time. There were no data on epilepsy and AED
treatment of the studied patients.
We evaluated the motor cortical excitability by determining
CMT and CSP in addition to measuring CMCT in our
RTT to explain the impact of altered motor cortical excitability
on the short CMCT.

RTT Rett syndrome

MECP2 methyl-CpG-binding protein 2 gene
CMCT central motor conduction time
TMS transcranial magnetic stimulation
CMT cortical motor threshold
CSP cortical silent period
AED antiepileptic drugs
MEP motor evoked potentials
RMT resting motor threshold
AMT active motor threshold
EMG electromyography
PTN pyramidal tract neurons
GABA gamma-aminobutyric acid