Random - from study notes Flashcards by Laura Engle

What are expected outcomes from unbalanced translocations?

Alternate: phenotypically normal, balanced translocation or normal

Adjacent 1: unbalanced translocation

Adjacent 2: unbalanced, usually lethal

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What signifies the Philadelphia chromosome?

BCR-ABL1
(chromosomes 22 and 9)

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What is the most common Robertsonian translocation?

13;14

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What cause of BWS has the highest recurrence risk in sibs?

genomic variant involving 11p15.5
- recurrence up to 50%

CDKN1C variant- 50%

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What types of variants in COL1A1 or COL1A2 OI type 1 vs types 2-4?

type 1 (classic non-deforming, least severe): non functional alleles: del, stop gain

types 2-4: dom neg causing misfolded protein

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What is the most common mutation causing achrondroplasia?

FGFR3 p.Gly380Arg

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What skeletal dysplasia syndrome can cause facial hair growth of the pregnant person carrying an affected fetus?

Antley Bixler
POR gene- cytochrome P450- makes steroids, including sex hormones –> virilizes the pregnant person

FGFR2 can cause Antley Bixler- skeletal features only!

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What are typical laboratory findings in lipoprotein lipase deficiency?

high triglycerides (leads to pancreatitis) and lipase

normal cholesterol

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What is the most common cause of transposition of the great arteries?

maternal diabetes

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What are common features of Holt Oram syndrome?

holes in heart- ASD or VSD
radial ray anomalies - absent thumbs
L arm > R arm

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What heart condition is characterized by L ventricular dilation and reduced EF?

DCM

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What is the common HFE mutation?

C282Y
homozygous penetrance <40% (women even lower)

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What is typical presentation of beta thalassemia at birth?

none, normal first six months because HbF is still protective

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What is the appropriate next step following high risk NIPS and normal US findings?

amniocentesis
-CVS not appropriate

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Do in frame or out of frame deletions cause DMD?

out of frame deletions –> disrupt reading frame –> no fxnl protein = DMD

in frame deletions = BMD

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What condition is consistent with hypoplasia of the cerebellar vermis and elongation of the cerebellar peduncles?

molar tooth sign = Joubert

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What condition is steroid sulfatase deficiency characteristic of?

XL icthyosis

also, decreased uE3 on serum screening

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Which MMR genes form heterodimers?

MLH1 + PMS2
MSH2 + MSH6

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Which MMR genes are obligate and will still be present if their partners are absent from staining?

MLH1 and MSH2

but if MLH1 and MSH2 absent so will be PMS2 and MSH6

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What cancer syndrome is associated with desmoid tumors?

FAP

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What cancer syndrome is associated with jaw cysts?

PTCH1 Gorlin syndrome

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What is the cutoff for 5 year risk for chemoprevention?

> 1.6%

not if:
-hx breast cancer
-mut +
-<35

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How do PARP inhibitors function?

block single strand DNA repair- kills cancer cells for BRCA because BRCA genes involved with double strand break repair

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What are findings of SRY translocation?

infertility, small testes, gynecomastia
80% of non syndromic 46 XX due to

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What percent of non syndromic 46 XX DSD are due to SRY translocation?

80%

What type of mutations lead to classic vs mild-moderate PKU?

biallelic LOF- classic 1 LOF, 1 missense -mild-moderate bilallelic missense- benign hyperphenylalanine

What condition is associated with a rotten cabbage smell?

tyrosinemia

What causes del/dups at mutational hotspots?

LCRs --> misalignment during non-allelic non homologous recombination

What is the genetic cause of Pallister Killian?

mosaic tetrasomy 12p

What causes hydrops fetalis?

anemia and subsequent heart failure

With confined placental mosaicism, what is their an increased risk of?

UPD! diploidy (correct amount) results from trisomy rescue to give viable fetus, possibility of UPD if two chromosomes from same parent are kept

What are some causes of false positives on NIPS?

confined placental mosaicism, vanishing twin, maternal mosaicism, maternal cancer

What are common features of Pallister- Hall?

post axial polydactyly, laryngeal cleft, hypothalmic hamartomas

What is the most common gene causing familial thoracic aortic aneurysms?

ACTA2

How would you differentiate the two conditions which cause facial port wine stains through somatic mosaic variants?

Klippel Trenaunay- PIK3CA: limb hypertrophy, varicose veins Sturge Weber - GNAQ: leptomeningeal angiomatosis, seizures, glaucoma

If a patient has anemia (Hgb <12), what conditions would you consider on the differential if it is microcytic (MCV <80)?

alpha or beta thal sideroblastic anemia

If a patient has anemia (Hgb <12), what conditions would you consider on the differential if it is normocytic (MCV 80-100)?

sickle cell G6PD spherocytosis pyruvate kinase deficiency

If a patient has anemia (Hgb <12), what conditions would you consider on the differential if it is macrocytic (MCV >100)?

Fanconi anemia Diamond blackfan anemia MTHFR

How would you differentiate a congenital presentation of SMA vs Pompe disease?

Pompe disease with HCM and elevated CK, SMA without cardiac features and normal CK

How does spinraza treat SMA?

promotes includes of SMN2 exon 7 --> increases functional protein

What is the most common cause of death in Freidreich's ataxia?

cardiomyopathy

What is a common laboratory elevation in ataxia telangiectasia?

elevated AFP also high CEA Low IgG, IgA, IgE

What are the effects of different types of variants in GJB2 on inheritance patterns?

frameshift variants (35delG) --> AR missense variants --> AD (dominant negative effect)

What are genetic causes for isolated cataracts in infancy?

AD or AR variants in crystallin genes, presentation at or after birth galactokinase deficiency, isolated cataracts, develops after birth only

Which MPS disorder is NOT characterized by CNS features?

MPS IV Morquio

What is the coefficient of inbreeding for cousins?

1/16 think 1/ (2^ number of people)

What is the resolution of karyotype, FISH, and CMA?

~ Karyotype: as small as 3-5 mb FISH: 100-200 kb CMA: as small as 50-100 kb

When does the NDJ event causing a 47, XYY karyotype occur?

only paternal MII

When does an event causing a mosaic karyotype occur?

mitosis very early in embyronic development

In what region of FMR1 is the tri-nucleotide repeat causing FMR1 related disorders?

promotor region

In what region of DMPK is the tri-nucleotide repeat causing the symptoms of myotonic dystrophy type 1?

3' UTR

When does the neural tube close?

week 4 development = week 6 GA

What sequence of the BRCA1 gene does the active estrogen receptor bind to?

consensus sequences at -35 and -10

What are the stop codons?

UAA UAG UGA

What pathway of repair is functional BRCA1 protein involved in ?

recombination repair

What is the criteria to diagnose NF1?

>=2 of the following criteria: - >= 6 CALs >5 mm pre puberty of 15 mm post - axillary / inguinal freckling - >= 2 neurofibromas or 1 plexiform - optic pathway glioma - >= 2 Lisch nodules or >= 2 choirodal abnormalities - distinctive osseus lesions (sphenoid dysplasia, anterolateral bowing of tibiba, pseudoarthritis of long bones) - parent (not FDR) who meets dx criteria - germline variant

What is the criteria to diagnose Marfan syndrome?

FBN1 variant + aortica root enlargement OR ectopic lentis

In what scenarios is a PTEN dx considered in children?

macrocephaly + any of the following: - autism or delays - dermatologic features - vascular features - GI polyps - thyroid or germ cell cancer

How is Cowden syndrome diagnosed clinically?

1 pathognomonic OR >= 2 major OR 1 major + >=3 minor OR >=4 minor

What are pathgnomonic features of Cowden syndrome?

- >= 6 facial papules where >=3 are trichelommas - cutaneous facial papules and oral mucosa papules - oral mucosa papules and acral keratosis - >= 6 palmoplantar keratoses

What are considered major features of Cowden syndrome?

- breast cancer - non medullary thyroid cancer - macrocephaly - endometrial cancer

What are considered minor features of Cowden syndrome?

- other thyroid nodules - ID - hamartomatous polyps - breast fibrocystic disease - lipomas - fibromas - GI tumors especially RCC - GI malformations - uterine fibroids

If a family member meets criteria for Cowden syndrome, what does another relative need for a clinical dx?

Fhx + 1 pathognomonic OR 1 major OR 2 minor OR hx BRR syndrome

What is the criteria to diagnose TSC?

pathogenic variant OR 2 major features OR 1 major 2 minor

What are considered major features of TSC?

- >= 3 angiofibromas or fibrous cephalic plaques - cardiac rhabdo - multiple cortical tumors or radial migration lines - >= 3 5mm hypomelanotic macules - lymphangioleiomyomatosis - multiple retinal nodular hamartomas - >= 2 renal angiomyoplipomas - shagreen patch - subependymal giant cell astrocytoma - >= 2 subependymal nodules - ungual fibromas

What are considered minor features of TSC?

- sclerotic bone lesions - confetti skin lesions - >=3 dental enamel pits - >= 2 intraoral fibromas - multiple renal cysts - nonretinal hamartomas - retinal chromic patch

How is a clinical dx of Fragile X ataxia syndrome made?

premutation carrier + 1 major clinical sign (intention tremor, gait ataxia) + 1 major radiograph sign (MRI white matter lesions- MCP sign)

What sphingolipodoses disorder is XL?

Fabry (GLA)

What genes cause Fabry, Gaucher, and Pompe disease?

Pompe - GAA = GSDII Gaucher- GBA (Bone pain) Fabry - GLA (x Linked)

What is the difference in copper buildup in Wilson vs Menkes disease?

Menkes: copper not transported well from blood, so high levels in blood but low in organs Wilson: not transported well from liver, so buildup in liver/ organs, can have low levels in blood

What DSD is XL?

adrenal hypoplasia congenita (NR0B1)

What is the most common inheritance for a condition characterized by sparse scalp/body hair, reduced ability to sweat, and congenital absence of teeth?

XL, EDA

What are possible genes/ inheritance patterns for Emery-Dreifuss?

most common- unknown 63% LMNA 27% (AD or AR) EMD 8% (XL) FHL1 (1%) (XL)

What is the deficiency in Fabry disease?

alpha galactosidase

What is the deficiency in Gaucher disease?

glucocerebrosidase

What enzyme is deficiency in Tay Sachs?

beta hexaminosidase - A

What gene and additional phenotype may be included in individuals with Prader willi syndrome cause by a larger 7 mb deletion vs a 5 mb deletion?

OCA2 - hypopigmentation of hair, skin, eyes