Overgrowth/Premature Aging/Pulmonary/Renal

Question 1

Beckwith-Wiedemann

11p15

Loss of Methylation at ____ in 50% of individuals

maternal chromosome

Answer 1

IC2

Question 2

paternal uniparental disomy chromosome 11p15 in 20% of patients

Answer 2

Beckwith-Wiedemann

Question 3

Beckwith-Wiedemann

Gain of methylation ___ in 5%

maternal chromosome

Answer 3

IC1

Question 4

CDKN1C heterozytgous maternally inherited pathogenic variants

Answer 4

Beckwith-Wiedemann Syndrome

40% of familial cases

5-10% on non-familial cases

Question 5

Malar flusing

spare frontal temporal hair

high bossed forehead

downslanting PF

Low narrow face

prominant narrow jaw

Learning disabilities

ht and HC >2SD

Answer 5

Soto Syndrome

NSD1 ; 5q35

AD inheritance

behavioral issues, advanced bone age, cardiac anomalies, CT/MRI cranial

Maternal preeclampsioa, scoliosis, seizures

Question 6

slow progressive cerebellar ataxia

oculomotor apraxia

cerebellar atrophy

decreased albumin

increase T. cholesterol

Normal AFP

r/o ataxia-telangiectasia

Answer 6

Ataxia with oculomotor apraxia type 1

APTX

Question 7

slow progressive cerebral ataxia

onset 3-30yo

initially normal development

increased AFP

cerebellar atrophy

exclude ataxia -telangiectasia

SETX

Answer 7

Ataxia with oculomotor apraxia type 2

Question 8

post natal growth failure

impaired vision and hearing

abnormal transcription coupled nucleotide excision repair

Answer 8

Cockayne Syndrome

ERCC6/ERCC8

AR inheritance

phenotypic spectrum: (XP-CS): facial freckling, early skin cancer, ID, spacicity, hypogonadism, short stature, no demylination

Question 9

• de novo* heterozygous
  c. 1824G>T (90%)

G608G Exon 11 (10%)

abnormal lamin A protien/ progerin

Answer 9

Hutchinson-Gilford

Progeria Syndrome

abnormal splicing leads to abnomal prelamin A protien with dominant negative effect

Accelerated aging features

FTT

Life span: 14.5 years

Morbitity/Mortality: Cardiac disease and cerbrovascular accidents

Question 10

SERPNA 1

Answer 10

Alpha 1 antitrypsin deficiency

chronic obstructive pulmonary disease (adults

liver disease (obstructive jaundice and , abd LFTs) -adults and children

panniculitis and c-ANCA (+) vacculitis

Smoking affects onset

increase risk for hepatocellular carcinoma

Question 11

progressive renal disease

chochlear abnormalities

ocular abnormalities - Ant Leniconus

isolated henaturia

Answer 11

Alport syndrome and thin BM Nephropathy

XL, AD, AR

COL4A5, COL 4A4, COL4A3

Question 12

Enlarged kidneys–>cysts

Cysts: liver, pancreas, intestine

intracranial aneurysms

Answer 12

AD polycystic kidney

PKD1, PKD2

Question 13

Fetal/Neonatal death

renal failure–> multiple small cysts

pulmonary hypoplasia–>oligohydramios

Answer 13

AR Polycystic kidney Disease

PKHD1

Question 14

Large deletions of PKD1 may also include this gene associated with a neurocutaneous genetic condition

Answer 14

TSC2

Tuberous sclerosis