Imprinting disorders Flashcards
Prader-Willi Genetics
-incidence of 1 in 10000-1 in 30000
-loss of paternal 15q11-13
+paternal deletion 70%
+maternal UPD 25%
+imprinting defects 3%
-SNURF/SNRP genomic imprinting
-sometimes OCA2 loss
Prader-Willi features
-severe hypotonia, FTT in infancy
-moderate ID, early DD onset
-behavioral problems
+hyperphagia-obesity in childhood
+skin picking, compulsiveness, temper
-small hands and feet
-short stature
-hypogonadism w/delayed puberty, adrenal problems
-characteristic facies
+almond-shaped eyes and strabismus
+thin down-turned upper lip
+narrowed temples and nasal bridge
Angelman genetics
- incidence of 1 in 12000-1 in 20000
- loss of maternal 15q11-13
- UBE3A expression lost (included in 15q)
- deletion of 15q11-13 (70% cases), mutation of maternal UBE3A (10% cases, leads to familial risk), or paternal UPD
Angelman features
-microcephaly
+seizures
+severe ID w/noticable DD by 6-12mo
-stiff, ataxic gait
-speech impairment, delay or no speech
-inappropriately happy affect with paroxysms of laughter
-characteristic facies
+protruding tongue
+widely spaced teeth
+prominent jaw/prognathism and thin upper lip
+hand abnormalities-smooth palms, broad thumbs, hand flapping movements
loss of OCA2
fair skin in PWS and angelman
detection and testing in PWS
-abnormal methylation in 98%
+if methylation abel FISH and karyo can find exact problem
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detection and testing in PWS
-abnormal methylation in 98%
+if methylation abnL FISH and karyo can find exact problem
-adrenal reserve assessment
+thyroid function tests
+growth hormone levels
-sleep studies for disturbances and apnea
PWS treatment
- GH supplementation
- dieting/food restriction with age
Angelman detection and testing
-abnormal methylation in 80% \+maternal deletion (60%) \+paternal UPD (3-5%) \+imprinting defect -maternal UBE3A variant (10%)
Beckwith-Wiedemann Genetics
*mostly sporadic occurrence
-abnormal expression of 11p15
+LOF of maternal IC2 (50%)
+paternal UPD (20%)
+mutation of maternal CDKN1 gene-AD (40% familial cases, 5-10% de novo)
+methylation of maternal IC1 (5%)
+duplication of paternally inherited region
BWS detection and testing
- normally detected by epigenetic studies
- less than 1% cases due to cytogentic abnormality
- increased risk in ART pregnancies
- can see discordance of affectedness in MZ twins, especially females
BWS features
-pre and postnatal overgrowth-macrosomia, macroglossia, visceromegaly
-omphalocele
-hypoglycemia
-advanced bone age
-increased risk for tumor growth-wilm’s tumor, hepatoblastoma
-hemihypertrophy (limb length discrepancy)
-characteristic facies
+large protruding tongue
+full eyes
+ear creases and posterior pits
+facial nevus flammeus/port wine stain
BWS management
- possible surgeries to reduce bone size discrepancy and tongue size
- abdominal wall repair
- correction of structural cardiac, GI and GU anomalies
- hypoglycemia treatment
- follow with pediatric nephrology and oncology, EI
Russell-Silver syndrome genetics
- incidence of 1 in 50000-1 in 100000
- hypomethylation of H19/IGF2 of 11p15.5 (40%)
- maternal UPD of chromosome 7 (10%)
Russel Silver phenotype
-pre and postnatal growth restriction with head sparing
+can also see growth asymmetry of the limbs
+final height tends to be up to 5ft
-micrognathia and down turned corners of the mouth, small triangular face
-CaLMs
-2-3 toe syndactly and 5th finger clinodactly
