phenotipic identification of neurological malformations: neuroradiology of syndromes
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Morning Seminars Thursday October 7. Phenotipic identification of neurological malformations: Neuroradiology of Syndromes. F. Triulzi Dept. of Radiology and Neuroradiology Children’s Hospital “V. Buzzi” Milan, Italy. Syndrome (σύνδρομος - "run together”). - PowerPoint PPT PresentationTRANSCRIPT
Phenotipic identification of neurological malformations:
Neuroradiology of Syndromes
Morning SeminarsMorning SeminarsThursday October 7Thursday October 7
F. TriulziF. TriulziDept. of Radiology and NeuroradiologyDept. of Radiology and Neuroradiology
Children’s Hospital “V. Buzzi”Children’s Hospital “V. Buzzi”Milan, ItalyMilan, Italy
SyndromeSyndrome (σύνδρομος - "run together”) (σύνδρομος - "run together”)
“association of several clinically recognizable features, signs, symptoms, phenomena or characteristics that often occur together “
Syndromes Neurological Neurological signs & symptomssigns & symptoms
CNSCNSanomaliesanomalies
NEURORADIOLOGY OF SYNDROMESSYNDROMES
David W Smith 1926-1981
Syndromology Syndromology DysmorphologyDysmorphology
Hooshang Taybi 1919-2006
Radiology of SyndromesRadiology of Syndromes
MIM ID #180849 RUBINSTEIN-TAYBI SYNDROME; RSTS
Gene map locus: 16p13.3, 22q13
•Clinical Features •Inheritance•Cytogenetics•Diagnosis•Clinical Management•Molecular Genetics•Genotype/Phenotype Correlations•Population Genetics
Initiated in the early 1960s by Dr. Victor A. Initiated in the early 1960s by Dr. Victor A. McKusickMcKusick as a catalog of as a catalog of mendelian traits and disorders, entitled mendelian traits and disorders, entitled Mendelian Inheritance in Man Mendelian Inheritance in Man
(MIM).(MIM).
http://www.ncbi.nlm.nih.gov/omim
•Nomenclature •Animal Model•History•Clinical Synopsis•References•Contributors•Creation Date•Edit History
NRX role in the diagnostic NRX role in the diagnostic evaluation of Syndromes with evaluation of Syndromes with
CNS involvement CNS involvement
A.A. Highly suggestiveHighly suggestive Can be in some rare case Can be in some rare case pathognomonicpathognomonicB.B.Suggestive
But never pathognomonicBut never pathognomonicC.DoubtfulC.Doubtful “ “Minor anomalies”Minor anomalies”D.Normal NRX studiesD.Normal NRX studies Rule out somethingRule out something
A number of definite anomalies A number of definite anomalies that can suggest a syndrome with that can suggest a syndrome with an high level of confidencean high level of confidence
A.A.Highly Highly suggestivesuggestive
Type AExamples
- AicardiAicardi- Delleman Delleman - De Morsier- De Morsier- Frontonasal dysplasia- Frontonasal dysplasia- Kallmann- Kallmann- Lhermitte-Duclos (Cowden Sy)Lhermitte-Duclos (Cowden Sy)- Walker-WarburgWalker-Warburg
FAKOMATOSISFAKOMATOSIS- NF 1- NF 1- NF 2- NF 2- Tuberous SclerosisTuberous Sclerosis- Sturge WeberSturge Weber- Encephalocraniocutaneous - Encephalocraniocutaneous lipomatosislipomatosis
Gene map locus: Xp22
AICARDI SYNDROME
•callosal agenesis•infantile spasms•chorioretinal lacunae•female
MIM ID %304050
Corpus callosum agenesisin a female
Intracranial cystsCortical anomalies
Subependymal heterotopia
*
*
Aicardi Syndrome
Aicardi Syndrome Corpus callosum agenesis XX
Intracranial cystsCortical anomalies
Subependymal heterotopia
23 GW female, US: CC agenesisMR: Aicardi Syndrome?
22.5 GW female, US: CC agenesisMR: Aicardi Syndrome?
MIM ID #182230
SEPTOOPTIC DYSPLASIADE MORSIER SYNDROME
Gene map locus: 3p21.2-p21.1
•optic nerve hypoplasia •pituitary gland hypoplasia •septum pellucidum agenesis
mutation in the homeobox gene HESX1 (601802).
Septum pellucidum agenesisPituitary hypoplasiaOptic nerves hypoplasia
Normal chiasm & pituitary
De Morsier Syndrome(septo-optic dysplasia)
Pituitary dwarfs + DSO
P.R.,m. 20m
SOD + polymicrogyria
P.R.,m. 20m
SOD + polymicrogyria
I.R.J.C.,m. 11 a
SOD + schizencephaly
I.R.J.C.,m. 11 a
SOD + schizencephaly
MIM ID #236670
WALKER-WARBURG SYNDROME
Gene map locus: 14q24.3, 9q34.1 genes encoding protein O-mannosyltransferase-1 (POMT1; 607423) and -2 (POMT2; 607439).
•hydrocephalus (H)•agyria (A),•retinal dysplasia (RD)•with or without encephalocele (+/-E).
Walker-Walker-WarburgWarburg
Walker-WarburgWalker-Warburg
Fetal MR
ENCEPHALOCRANIOCUTANEOUS LIPOMATOSIS MIM ID %613001
•profound mental retardation•early onset of seizures•unilateral temporofrontal lipomatosis•ipsilateral cerebral and leptomeningeal lipomatosis•cerebral malformation and calcification•lipomas of the skull, eye, and heart
Affected sideArachnoid cystLipomaMeningeal calcificationsVentricular dilatationCortical malformation
Encephalocraniocutaneous Lipomatosis
Evidence of one or more anomalies Evidence of one or more anomalies that are mandatory to define a that are mandatory to define a syndrome, but remain non specificsyndrome, but remain non specific
B.SuggestivB.Suggestivee
Type BGeneric Anomalies
Corpus callosum agenesisCerebellar hypoplasiaMalformations of cortical develpmentWhite matter hypoplasiaMicrocephaly
Type BExamples
- Andermann- Andermann- Atassia-- Atassia-teleangectasiateleangectasia- CHARGE- CHARGE- Cockayne- Cockayne- Ehlers-Danlos- Ehlers-Danlos- Nevo epidermico- Nevo epidermico- Fragile X- Fragile X- Hypomelanosis of Ito- Hypomelanosis of Ito- Incontinentia - Incontinentia pigmentipigmenti- Klippel-Trenaunay- Klippel-Trenaunay- Marinesco-Sjogren- Marinesco-Sjogren- Miller-Dieker- Miller-Dieker
- Moebius- Moebius- Goldenhar- Goldenhar- Pallister-Hall- Pallister-Hall- PEHO- PEHO- Rendu-Osler- Rendu-Osler- Rubistein-Taybi- Rubistein-Taybi- Stoll-Charrow-Poznanski- Stoll-Charrow-Poznanski- Toriello-CareyToriello-Carey- Trichothiodystrophy- Von Hippel-Lindau- Von Hippel-Lindau- WolframWolfram- Wolf-HirschornWolf-Hirschorn
MILLER-DIEKER LISSENCEPHALY SYNDROME MIM ID #247200
Gene map locus: 17p13.3
•lissencephaly •microcephaly•wrinkled skin over the glabella and frontal suture•prominent occiput•narrow forehead•downward slanting palpebral fissures•small nose and chin, cardiac malformations•hypoplastic male extrenal genitalia•growth retardation
Miller Miller DiekerDieker lissencephaly
TRICHOTHIODYSTROPHY MIM ID #601675
Gene map locus: 6q25.3, 2q21,
•brittle hair and nails•ichthyotic skin•physical and mental retardation•hypomyelination
HypomyelinationHypomyelinationTrichothiodystrophy
HypomyelinationHypomyelination
Cerebellar Cerebellar atrophyatrophy
HypodontiaHypodontia
Corpus callosum agenesis
Minor subtle anomalies, that Minor subtle anomalies, that can however suggest a can however suggest a syndrome in case of a positive syndrome in case of a positive clinical hystoryclinical hystory
C.DoubtfC.Doubtfulul
Type C
Corpus callosumCerebellum-brainstemCortical gyri
Minor dysmorphic features of:
Corpus callosum is not partly or totally absent…
…But DYSMORPHIC
BorjesonBorjesonForssmanForssmanLehmannLehmann
•severe mental defect•epilepsy•hypogonadism•hypometabolism•marked obesity•swelling of subcutaneous tissue of face•narrow palpebral fissure•large but not deformed ears Gene map locus: Xq26.3
MIM ID #301900
Kabuki make-upKabuki make-upsyndromesyndrome
•mental retardation•postnatal dwarfism•long palpebral fissures•broad and depressed nasal tip•large prominent earlobes•high-arched palate•scoliosis•short fifth finger•persistence of fingerpads•radiographic abnormalities of the vertebrae•recurrent otitis media in infancy
MIM ID #147920mutation in the MLL2 geneon chromosome 12q12-q14.
Pallister-KillianMIM ID #601803
mosaicism for tetrasomy of chromosome 12p.
•profound mental retardation•seizures•streaks of hypo- or hyper-pigmentation•prominent forehead•sparse anterior scalp hair•flat occiput, hypertelorism•short nose with anteverted nostrils•flat nasal bridge•short neck..
Pallister-Killian
CostelloMIM ID #218040
mutations in the HRAS gene (190020)
•characteristic coarse facies•short stature•distinctive hand posture and appearance•severe feeding difficulty•failure to thrive•cardiac anomalies•developmental disability.
Costello
Del 1 q Translocation 3y
Chromosomopathies
Del 1 q
Translocation 3y
2 months 3 5
6 6,5 8 8,5
9,5 11 12,5 15
4
Normal corpus callosum development
2 3 5
6 6,5 8 8,5
9,5 11 12,5 15
4
Genu Body
Hystmus Splenium
4 years 5 6 8
10 12 14 18
Normal corpus callosum development…
…and Syndromes
Band thick to thin
short and thickhumpty dumpty
Short and irregular
Minor dysmorphismsin Syndromes
Very frequent
Minor dysmorphismsin Syndromes
Very low specificityDifferent Syndromes – Same anomalies
“Cerebral phenotype”
Needs quantitation
Voxel based morphometry??DTI??
Williams syndromes Marenco et al PNAS 2007;104:15117-22
Connectivity in Syndromes
Morning SeminarsMorning SeminarsThursday October 7Thursday October 7
Thank you for your attention