Genetics Flashcards
5p deletion
Cri-du-chat syndrome
- Weak/ cat like cry, hypotonia, failure to thrive, dev delay
- microcephaly, low set ears, hypertelorism, broad nasal bridge.
- partial chr del
22q11 microdeletion
DiGeorge sydnrome
- thymic aplasia (T cell def), hypoparathyroidism (hypoCa)
- Assoc tetralogy of fallot, truncus arteriosus, transposition of great arteries
- hypertelorism, low set ears, micrognathia, cleft palate
*Gold standard test: fluorescence in situ hybridization
15p deletion
Prader-Willi syndrome
- Uniparenteral disomy
- assoc cogn dysfx & behavioral disturbances
Robertsonian translocation of chr 14 and 21
Down syndrome
fibrillin-1 mutation
Marfan syndrome
- Cystic medial necrosis of the aorta & jt hypeE.
- high arched palate with crowded teeth and narrow face.
frataxin mutation (GAA repeat)
Friedreich ataxia
- mito protein mut - imp in iron homeostasis and resp fx
- spinocerebellar degen
- spinal ataxia
- assoc hypertrophic cardiomyopathy
Tuberin and harmatin mutation
tuberous sclerosis
*cardiac rhabdomyomas in ven walls and AV valves, cutaneous angiofibromas (adenomas sabaceum), central venous system hamartomas, renal cysts
45,X
Turner syndrome
*assoc bicuspid aortic valve, coarctation of the aorta
47,XX, +18
Edwards syndrome (meiotic nondisjunction)
- Micrognathia, low set ears, prominent occiput, rocker bottom feet, sign hypertonia, clenched hands with overlapping fingers
- VSD, PDA
- Horseshoe kidney
- Meckel’s diverticulum, malrotation
- fetal growth restriction, intellectual disability.
Diagnosis:
- Micrognathia, low set ears, prominent occiput, rocker bottom feet, sign hypertonia, clenched hands with overlapping fingers
- VSD, PDA
- Horseshoe kidney
- Meckel’s diverticulum, malrotation
- fetal growth restriction, intellectual disability.
Edwards syndrome
47,XX, +18
Trisomy 18
Diagnosis:
- thymic aplasia (T cell def), hypoparathyroidism (hypoCa)
- Assoc tetralogy of fallot, truncus arteriosus, transposition of great arteries
- hypertelorism, low set ears, micrognathia, cleft palate
DiGeorge syndrome
22q11 deletion
midline facial defects: microcephaly/ holoprosencephaly,
- cleft lip/palate
- microphthalmia
- Cutis aplasia
- Polydactyly
- *Omphalocele, umbilical hernia
Trisomy 13, Pautau syndrome
*Also renal/cardiac defects
Diagnosis:
Upslanting palebral fissure, low set small ears, single transverse palmar crease, hypotonia.
Trisomy 21, Down syndrome
Trinucleotide CTG repeat expansion
- muscle weakness
- anticipation
AD, Myotonic dystrophy
- expansion on DMPK gene
- untranslatable mutant mRNA = disrupt gene expression»_space; disorganized T tubules»_space; weakness and type I myofiber atrophy + skm Cl channel dysfx»_space; delayed m relaxation myotonia
- childhood form: cognitive & behav problems (dev over time)
- adult: progressive m weakness (face, hands, ankles), myotonia, cardiac abn (arrhythmias, cardiomyopathy), cataracts, frontal balding, ins resistance.
- Dx: genetic test
Dx:
muscle weakness/ exercise intolerance, lactic acidosis (in severe), no myotonia
mitochondrial myopathies
X-linked frameshift mutation in dystrophin
Duchenne & Becker muscular dystrophy
*Proximal m. weakness intially
Dx:
Infertility, situs inversus, chronic sinusitis, bronchiectasis.
*immotile cilia d/t AR microtubular defect in the dynein arm.
Kartagener syndrome
Dx:
Paternal gene del 15q-
maternal genes are silenced
Prader-Willi syndrome (PWS)
*short stature, obesity, hypotonia, hypogonadism.
Dx:
Maternal gene del 15q-
paternal gene silenced
Angelman syndrome
*microcephaly, ataxia, flapping movements, freq laughter (happy puppet)
CGG repeats
Fragile X syndrome
*Neurobehav problems, prominent forehead, large protruding ears, long/narrow face, prominent chin, macroorchidism.
AR mutation of ATP7B
Wilson disease
*hepatic copper accum»_space; leark from damaged hepatocytes»_space; deposits in tissues (basal ganglia, cornea)
- acute liver failure/ chronic hep/ cirrhosis
- parkinsonism, gait disturbance, dysarthria
- depression, personality changes, psychosis
Dx: decr seruloplasmin, incr urinary copper excretion
- Kayser-Fleischer rings on slit-lamp exam
- liver bx: incr copper content
Tx: Chelators (D-penicillamine, trientine)
Zinc (interferes with copper abs)
CAG repeats expansion
Huntington disease (HD) HTT gene
Most common ataxia Dx
neurologic dysfx cardiomyopathy, DM
Friedreich ataxia
X-linked MECP2 gene
Rett syndrome
- Dev of hand wringing, neurodev DO
- GIRL
- loss of motor and language skill, stereotypic hand movements
- deceleration of head growth.
- seizures, intellectual disability, autistic features, breathing abn.
X linked recessive def HGPRT (hypoxanthine guanine phosphoribosyltransferase)
Lesch-Nyhan syndrome
incr uric acid
hypotonia, invol move (hand wrining)
*gout, self multilating behavior (lip/ finger biting)
Lysosomal storach dz
Def in Beta-hexosaminidase (Hex A)
Tach Sachs dz
regression motor skill (2-6mo)
*macrocephaly
*cherry red spot on macula
MECP2 gene mutation
- rare, Girls > boys
- onset: 6-18 mo
Rett syndrome
*sporadic, X chr
arrested brain dev (not neurodegen)
*initially normal dev»_space; loss of speech, loss of purposeful hand use, sterotypical hand movement (wringing), gait abn, seizures, microcephaly
