שינוים גנומיים בשיתוק מוחין קריפטוגני

Microarray Analysis for Identifying Genetic causes for Idiopathic CP-a Preliminary Study Reeval Segel1*, Hilla Ben-Pazi2*, Sharon Zeligson1, Aviva

Fatal-Valevski3, Adi Aran2, Varda Gross2, Nira heinbaum3, Dorit Shmueli4, Dorit Lev5, Shira Perlberg1, Ephrat Levi-Lahad1

 1Medical Genetics Institute Shaare Zedek Medical Center, Jerusalem;2Pediatric Neurology Unit, Shaare Zedek Medical Center, Jerusalem;3 Pediatric Neurology Unit, Dana Children’s Hospital, Tel-Aviv;4Jerusalem Child Development Center, Clalit, Jerusalem;5 Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon;

Genetic factors in CP

“Genomic insights into the causes and classification of the cerebral palsies”

Moreno-De-Luca et al. Lancet Neurol 2012

Complex neurological disorder There are instances the etiology is clear cut other cases- no etiology is apparent

Aim-

1) To identify the non- acquired CP

2) To identify genomic rearrangements in individuals

with non- acquired CP by microarray analysis.

Rationale for sequences Sequence

“Single incident caused a chain of events

leading to a syndromatic appearance” i.e. Pierre Robin sequence

Similar to epilepsy (ILAE)- Multi level axes Not each case can be categorized

event

MethodsMethods Summary letters reviewed according to 3

axes: History Anatomic distribution Imaging

Classified accordingly into 3 sequences Hypoxic- ischemic sequence Hemispheric lesion sequence Periventricular lesion sequence

computerized summary letters reviewed.

Each letter was searched for parameters ~ 1-2 minutes per case.

Hypoxic Ischemic SequenceHistory:

• Term infant• Hypoxia-ischemia

• Full resuscitation • Apgar <7 at 5 min • Sarnat grade >2

Anatomic distribution:• QuadriplegiaImaging: • Bihemispheric • Deep grey matter injury• Normal

Hemispheric Lesion SequenceHistory: • Term infantAnatomic distribution: • hemiplegia Imaging: • Hemispheric lesion

• Stroke• Tumor• AVM

Periventricular Leucomalacia- PVL SequenceHistory: • Prematurity of 24-34WAnatomic distribution: • Di, Hemi, quadriplegia Imaging: • PVL

RESULTS

(n=195)

Preliminary- Genetic Results

47 cases 24 had 35 genomic rearrangements

(GR) 9 de novo 10 inherited 16 ongoing

7 had multiple GR

Startle שנים- 13ח.פ. בת היפוטוניה אקסיאלית ודיסטוניה בגפיים קוגניציה שמורה יחסית

.אך ישנה ירידה לאחרונה בעיות שינהמיקרוצפליהקשיי נשימהdel22q11.21. 2.8Mb

היפוקלצמיה

היפוקלצמיה

SOBIN et al 2005

להורים אשכנזים לא קרובי 2/4 משפחה

שנים10בן ,דיסמורפי, שפה שסועהשיער שיבהלאחרונה דיסטוניה

שנים5בן ספסטיק דיפלגיה

מתקדמתADHD

Different deletion

-Any ideas?

Different deletion

-Any ideas?

5.2 Mb Del 2 p23.1-p22.2

Spastin

1.96Mbdel19q13.12mitochondrial enzymesZinc fingers unknown

A whole deletion would be missed

A whole deletion would be missed

Thanks SZMC:

Reeval Segel, Sharon Zeligson, Shira Perlberg, Ephrat Levi-Lahad

Adi Aran, Varda Gross DANA:

Aviva Fatal-Valevski, Nira Sheinbaum CDC Clalit

Dorit Shmueli Wolfson

Dorit Lev