sotos syndrome, genetics, radiology, craniofacial abnormalities, management
TRANSCRIPT
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Adnan Rashid, MDThe Children’s Hospital of Philadelphia (CHOP)University of Pennsylvania, PA, USA
SOTOS SYNDROME
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Outline Manifestations Patho-physiology & Genetics Diagnostic parameters Management General outcome Other Genetic overgrowth syndromes
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Manifestations
Craniofacial Abnormalities Growth Abnormalities Performance & Behavioral
Abnormalities Neonatal Problems Other associations
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Craniofacial Abnormalities-Dolichocephaly
-Receding hairline -Epicanthic Folds-Flat Nasal bridge-Flushingof cheeks and nose-Apparent hypertelorism (normal measurements)
-“Antimongoloid slant“ (DSPF)
-Prominent pointed chin
Rio M et al. J Med Genet 2003;40:436-440©2003 by BMJ Publishing Group Ltd
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Typical MRI findings
Ventricular abnormalities: -Ventriculomegaly -Prominence of trigone and occipital horns
Midline Defects: (increased risk of MR) -Corpus callosum hypoplasia/ agenesis -persistence of cavum septum and cavum velum interpositumNo measure needed if normal CSF
pressure
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Growth Abnormalities(Length>Weight)
Prenatal onset Length remains at or above 97th %tile
throughout childhood and adolescence.
Advanced osseous maturation in childhood
Final height…………………….. WNL Large Hands and feet( >50th %ile
even when plotted for height age)
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Performance Abnormalities MOTOR: Poor Coordination (Non progressive,
gross>fine) Hyper-reflexia Hypo-tonia (poor sucking may need
NGF) Delayed Motor function Variable Mental Deficiency: (IQ 40-129)
Mean IQ= 78 Expressive language delay Significant behavioral abnormalities (Due to
difficulty in socializing)
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Neonatal Problems
large head circumference, body length & weight
Poor suckling (may need NGT) Difficulty Breathing Jaundice Constipation Otitis Media with conductive hearing
loss Delayed early developmental
milestones
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Other associations: EEG abnormalities and Seizures Ophthalmologic : Strabismus, Nystagmus, Cataracts, Iris
Hypoplasia, Glaucoma, Optic disk pallor and retinal atrophy
Cardiac and Urogenital Defects (>japan) Conductive hearing loss Cutis laxa(MCTD) Kypho-scoliosis , Joint
laxity Abnormal Glucose tolerance(14%) Malignancy(2.2%) No screening recommended
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Etiology
Haplo-insufficiency of NSD-1: (Nuclear Receptor SET-domain-containing protein, 5q35) NSD1: (Histone-Lysine Methyltransferase family) Methylates: H4 K20 and H3 K36 influences Transcription
NSD1 deletions: paternal origin with advanced of paternal age
- Sporadic >AD Reference article: J Med Genet
2003;40:436-440doi:10.1136/jmg.40.6.436
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Phenotype
Independent of underlying mutation except:
Learning disability and Severe
Mental Retardation; are a feature of deletions.
Moderate speech delay; is more common with point mutations.
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Diagnostic Strategy
clinical findings
+ molecular genetic testing
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Clinical Diagnostic parameters(by Cole and Hughes)
Overgrowth(growth >2 SD): Large body, Hands & Feet Delayed development : motor, cognitive, social and
Speech Bone age : (Xray- Hand) Advanced Facial gestalt & Macrocephaly(>2 SD): are mandatory Reference article: J Med Genet 1994;31:20-32 doi:10.1136/jmg.31.1.20
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ManagementEvaluations Following Initial Diagnosis Echocardiogram and renal ultrasound (VUR) Glucose tolerance tests in family members IGF-1 & Insulin level(raised) T3/T4/TSH (Hypo and hyperthyroidism) Referral for Audiologic-assessment Genetic counseling and consultation Prenatal Diagnisis( 12wk-CVS, 15 wk amnio) Prevention of Secondary Complications(Antibiotic
prophylaxis if proven VUR) Treatment of Manifestations Education
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General outcome
Muscle tone improves steadily along with better speech.
Sotos syndrome primarily alters developmental timing
despite early trends, the adult with Sotos syndrome may be within the normal range of height and intellect.
Ref: Arch Dis Child 1999;80:339-342 doi:10.1136/adc.80.4.339
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Genetic overgrowth syndromes Fragile X Syndrome Weaver Syndrome( NSD1 mutation) Marshall-Smith Syndrome Beckwith-Wiedemann Syndrome Simpson-Golabi-Behmel Syndrome
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References:
1)Ref: PMID: 20301652 [PubMed] 2) Arch Dis Child 1999;80:339-342 doi:10.1136/adc.80.4.3393) J Med Genet 2003;40:436-440doi:10.1136/jmg.40.6.436 4) J Med Genet 1994;31:20-32 doi:10.1136/jmg.31.1.205) Smith's Recognizable Patterns Of Human Malformation
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THANK YOU!