General genetics / metabolic 1 Flashcards
Hemochromatosis
features
gene(s)
inheritance
- iron overload
- fatigue, arthralgia, abdominal pain
- HFE gene
- AR inheritance
OTC
features
gene(s)
inheritance
OTC=ornithine transcarbamylase deficiency
- neonatal hyperammonemia, coma
- OTC gene
- XL inheritance
47,XXX
features
cause
- 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
47,XYY
features
cause
- no abnormal phenotype; normal fertility; tall; increased risk for ADHD & impulsiveness
- YY sperm from paternal nondisjunction at meiosis II
Down syndrome
features
-dysmorphic features; hypotonia; ID; 1/2 w/CHD
Klinefelter syndrome
features
- tall/thin; hypogonadism at puberty & underdeveloped secondary sex characteristics
- effect of increased maternal age
Trisomy 13
features
-growth retardation; severe ID; severe CNS malformations; cleft lip and palate; ocular abnormalities; polydactyly; clenched fists; rocker-bottom feet
Trisomy 18
features
-FTT; severe MR; heart malformations; clenched fists; rocker-bottom feet
Pallister-Killian syndrome
features
gene(s)
inheritance
- hypotonia; ID; dysmorphic features; sparse hair & skin findings
- isochromosome 12p
- mosaic; not inherited
Turner syndrome
features
gene(s)
inheritance
- short stature; ovarian dysgenesis; few undergo puberty; cystic hygroma; cardiac & renal anomalies; sensorineural hearing deficit
- 45,X (may be mosaic)
Ehlers-Danlos syndrome
features
gene(s)
inheritance
- skin hyperextensibility, abnormal wound healing, joint hypermobility
- half have mutation in COL5A1 or COL5A2 genes
- AD inhertiance
Loeys-Dietz syndrome
features
gene(s)
inheritence
- vascular findings, skeletal manifestations, some with craniofacial manifestations; mean age of death: 26y
- TGFBR1, TGFBR2, SMAD3, TGFB2 genes
- AD inheritance
Marfan syndrome
features
gene(s)
inheritance
- tall stature; skeletal, ocular, cardiovascular, pulmonary, skin, dural abnormalities
- FBN1 gene
- AD inheritance
Achondroplasia
features
gene(s)
inheritance
- short stature; megalencephaly; spinal cord compression; midface hypoplalsia w/prominent forehead
- FGFR3 gene
- AD inheritance
FGFR3 gene mutations
- achondroplasia caused by gain-of-function mutations
- 2 mutations both resulting in Gly380Arg account for >99% of cases
CHARGE syndrome
features
gene(s)
inheritance
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
Tay-Sachs disease
features
gene(s)
inheritance
- regression of motor skills, loss of vision, seizures
- HEXA gene
- AR inheritance
Alzheimer’s disease
features
gene(s)
inheritance
- 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
Becker muscular dystrophy
features
gene(s)
inheritance
- muscle weakness; cardiac involvement
- DMD gene
- XL inheritance
Duchenne muscular dystrophy
features
gene(s)
inheritance
- motor delays; muscle weakness; cardiac involvement (also in female carriers)
- DMD gene
- XL inheritance
Rett syndrome
features
gene(s)
inheritance
- 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)
Neurofibromatosis
features
gene(s)
inheritance
- neurological, musculoskeletal, opthalmological, skin abnormalities
- NF1 gene
- AD inheritance
Xeroderma pigmentosum
features
gene(s)
inheritance
- sun sensitivity; ocular involvement; risk of skin and eye neoplasms
- XPA, XPC, ERCC2, POLH genes
- AR inheritance
Beckwith-Wiedemann syndrome
features
gene(s)
- macroglossia; macrosomia; AWDs; hemihyperplasia; embryonal tumors; normal intelligence
- 11p15.5 mom is silenced OR CDKN1C gene mutations
Russell-Silver syndrome
features
gene(s)
- triangular facies; growth retardation w/normal head circumference; DD/ID
- 11p15.5 dad is silenced; or chromosome 7
Prader-Willi syndrome
features
gene(s)
- infancy: hypotonia, feeding difficulties; DD
- childhood: overeating/obesity; ID; underdeveloped genitals
- 15q11.2-q13 dad is silenced
Angelman syndrome
features
gene(s)
- DD; ID; happy demeanor; ataxia; microcephaly; seizures; hand-flapping
- 15q11.2-q13 mom is silenced; or UBE3A gene mutation
SLOS
features
gene(s)
inheritance
- growth retardation; ID; multiple malformations
- DHCR7 gene
- AR inheritance
NF1 diagnostic criteria
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
Marfan diagnostic criteria
in absence of family hx
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
Marfan diagnostic criteria
with positive family hx
a first-degree relative plus any of the following:
- ectopia lentis
- systemic score 7+
- aortic root enlargement
Galactosemia
features
gene(s)
inheritance
- severe symptoms in untreated infants; with lactose-restriction still risk for DD and POI
- GALT gene
- AR inheritance
