General genetics / metabolic 1

Question 1

Hemochromatosis
features
gene(s)
inheritance

Answer 1

• iron overload
• fatigue, arthralgia, abdominal pain
• HFE gene
• AR inheritance

Question 2

OTC
features
gene(s)
inheritance

Answer 2

OTC=ornithine transcarbamylase deficiency

• neonatal hyperammonemia, coma
• OTC gene
• XL inheritance

Question 3

47,XXX
features
cause

Answer 3

• tall w/no abnormal phenotype; usually fertile; higher incidence of low IQ and learning problems
• effect of increased maternal age; most result from error in maternal meiosis I

Question 4

47,XYY
features
cause

Answer 4

• no abnormal phenotype; normal fertility; tall; increased risk for ADHD & impulsiveness
• YY sperm from paternal nondisjunction at meiosis II

Question 5

Down syndrome

features

Answer 5

-dysmorphic features; hypotonia; ID; 1/2 w/CHD

Question 6

Klinefelter syndrome

features

Answer 6

• tall/thin; hypogonadism at puberty & underdeveloped secondary sex characteristics
• effect of increased maternal age

Question 7

Trisomy 13

features

Answer 7

-growth retardation; severe ID; severe CNS malformations; cleft lip and palate; ocular abnormalities; polydactyly; clenched fists; rocker-bottom feet

Question 8

Trisomy 18

features

Answer 8

-FTT; severe MR; heart malformations; clenched fists; rocker-bottom feet

Question 9

Pallister-Killian syndrome
features
gene(s)
inheritance

Answer 9

• hypotonia; ID; dysmorphic features; sparse hair & skin findings
• isochromosome 12p
• mosaic; not inherited

Question 10

Turner syndrome
features
gene(s)
inheritance

Answer 10

• short stature; ovarian dysgenesis; few undergo puberty; cystic hygroma; cardiac & renal anomalies; sensorineural hearing deficit
• 45,X (may be mosaic)

Question 11

Ehlers-Danlos syndrome
features
gene(s)
inheritance

Answer 11

• skin hyperextensibility, abnormal wound healing, joint hypermobility
• half have mutation in COL5A1 or COL5A2 genes
• AD inhertiance

Question 12

Loeys-Dietz syndrome
features
gene(s)
inheritence

Answer 12

• vascular findings, skeletal manifestations, some with craniofacial manifestations; mean age of death: 26y
• TGFBR1, TGFBR2, SMAD3, TGFB2 genes
• AD inheritance

Question 13

Marfan syndrome
features
gene(s)
inheritance

Answer 13

• tall stature; skeletal, ocular, cardiovascular, pulmonary, skin, dural abnormalities
• FBN1 gene
• AD inheritance

Question 14

Achondroplasia
features
gene(s)
inheritance

Answer 14

• short stature; megalencephaly; spinal cord compression; midface hypoplalsia w/prominent forehead
• FGFR3 gene
• AD inheritance

Question 15

FGFR3 gene mutations

Answer 15

• achondroplasia caused by gain-of-function mutations

- 2 mutations both resulting in Gly380Arg account for >99% of cases

Question 16

CHARGE syndrome
features
gene(s)
inheritance

Answer 16

C: coloboma
H: heart defects
A: atresia of the choanae
R: retardation of growth/development
G: genital abnormalities
E: ear anomalies
-CHD7 gene
-AD inheritance

Question 17

Tay-Sachs disease
features
gene(s)
inheritance

Answer 17

• regression of motor skills, loss of vision, seizures
• HEXA gene
• AR inheritance

Question 18

Alzheimer’s disease
features
gene(s)
inheritance

Answer 18

• middle to late adulthood onset of progressive dementia
• early-onset genes: APP, PSEN1, PSEN2
• late-onset: no mendelian causes identified, but APOE gene e4 allele associated w/disease

Question 19

Becker muscular dystrophy
features
gene(s)
inheritance

Answer 19

• muscle weakness; cardiac involvement
• DMD gene
• XL inheritance

Question 20

Duchenne muscular dystrophy
features
gene(s)
inheritance

Answer 20

• motor delays; muscle weakness; cardiac involvement (also in female carriers)
• DMD gene
• XL inheritance

Question 21

Rett syndrome
features
gene(s)
inheritance

Answer 21

• normal prenatal/neonatal growth/development; rapid onset of neurological symptoms and loss of milestones 6-18 months; wringing and flapping movements of hands and arms
• MECP2 gene
• XL (lethal in hemizygous males)

Question 22

Neurofibromatosis
features
gene(s)
inheritance

Answer 22

• neurological, musculoskeletal, opthalmological, skin abnormalities
• NF1 gene
• AD inheritance

Question 23

Xeroderma pigmentosum
features
gene(s)
inheritance

Answer 23

• sun sensitivity; ocular involvement; risk of skin and eye neoplasms
• XPA, XPC, ERCC2, POLH genes
• AR inheritance

Question 24

Beckwith-Wiedemann syndrome
features
gene(s)

Answer 24

• macroglossia; macrosomia; AWDs; hemihyperplasia; embryonal tumors; normal intelligence
• 11p15.5 mom is silenced OR CDKN1C gene mutations

Question 25

Russell-Silver syndrome features gene(s)

Answer 25

- triangular facies; growth retardation w/normal head circumference; DD/ID - 11p15.5 dad is silenced; or chromosome 7

Question 26

Prader-Willi syndrome features gene(s)

Answer 26

- infancy: hypotonia, feeding difficulties; DD - childhood: overeating/obesity; ID; underdeveloped genitals - 15q11.2-q13 dad is silenced

Question 27

Angelman syndrome features gene(s)

Answer 27

- DD; ID; happy demeanor; ataxia; microcephaly; seizures; hand-flapping - 15q11.2-q13 mom is silenced; or UBE3A gene mutation

Question 28

SLOS features gene(s) inheritance

Answer 28

- growth retardation; ID; multiple malformations - DHCR7 gene - AR inheritance

Question 29

NF1 diagnostic criteria

Answer 29

meet 2 or more: - 6+ CALMs - 2+ neurofibromas OR 1 plexiform neurofibroma - freckling in axillary or inguinal regions - optic glioma - 2+ Lisch nodules - distinctive osseus lesion - 1st degree relative w/NF1

Question 30

Marfan diagnostic criteria | in absence of family hx

Answer 30

any of the following: - aortic root enlargement AND ectopia lentis - aortic root enlargement AND a pathogenic FBN1 variant - aortic root enlargement AND a systemic score 7+ - ectopia lentis AND a pathogenic FBN1 variant associated with aortic enlargement

Question 31

Marfan diagnostic criteria | with positive family hx

Answer 31

a first-degree relative plus any of the following: - ectopia lentis - systemic score 7+ - aortic root enlargement

Question 32

Galactosemia features gene(s) inheritance

Answer 32

- severe symptoms in untreated infants; with lactose-restriction still risk for DD and POI - GALT gene - AR inheritance