Genetics

Question 1

5p deletion

Answer 1

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

Question 2

22q11 microdeletion

Answer 2

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

Question 3

15p deletion

Answer 3

Prader-Willi syndrome

• Uniparenteral disomy
• assoc cogn dysfx & behavioral disturbances

Question 4

Robertsonian translocation of chr 14 and 21

Answer 4

Down syndrome

Question 5

fibrillin-1 mutation

Answer 5

Marfan syndrome

• Cystic medial necrosis of the aorta & jt hypeE.
• high arched palate with crowded teeth and narrow face.

Question 6

frataxin mutation (GAA repeat)

Answer 6

Friedreich ataxia

• mito protein mut - imp in iron homeostasis and resp fx
• spinocerebellar degen
• spinal ataxia
• assoc hypertrophic cardiomyopathy

Question 7

Tuberin and harmatin mutation

Answer 7

tuberous sclerosis
*cardiac rhabdomyomas in ven walls and AV valves, cutaneous angiofibromas (adenomas sabaceum), central venous system hamartomas, renal cysts

Question 8

45,X

Answer 8

Turner syndrome

*assoc bicuspid aortic valve, coarctation of the aorta

Question 9

47,XX, +18

Answer 9

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.

Question 10

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.

Answer 10

Edwards syndrome
47,XX, +18
Trisomy 18

Question 11

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

Answer 11

DiGeorge syndrome

22q11 deletion

Question 12

midline facial defects: microcephaly/ holoprosencephaly,

• cleft lip/palate
• microphthalmia
• Cutis aplasia
• Polydactyly
• *Omphalocele, umbilical hernia

Answer 12

Trisomy 13, Pautau syndrome

*Also renal/cardiac defects

Question 13

Diagnosis:

Upslanting palebral fissure, low set small ears, single transverse palmar crease, hypotonia.

Answer 13

Trisomy 21, Down syndrome

Question 14

Trinucleotide CTG repeat expansion

• muscle weakness
• anticipation

Answer 14

AD, Myotonic dystrophy

• expansion on DMPK gene
• untranslatable mutant mRNA = disrupt gene expression&raquo_space; disorganized T tubules&raquo_space; weakness and type I myofiber atrophy + skm Cl channel dysfx&raquo_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

Question 15

Dx:

muscle weakness/ exercise intolerance, lactic acidosis (in severe), no myotonia

Answer 15

mitochondrial myopathies

Question 16

X-linked frameshift mutation in dystrophin

Answer 16

Duchenne & Becker muscular dystrophy

*Proximal m. weakness intially

Question 17

Dx:

Infertility, situs inversus, chronic sinusitis, bronchiectasis.

*immotile cilia d/t AR microtubular defect in the dynein arm.

Answer 17

Kartagener syndrome

Question 18

Dx:

Paternal gene del 15q-
maternal genes are silenced

Answer 18

Prader-Willi syndrome (PWS)

*short stature, obesity, hypotonia, hypogonadism.

Question 19

Dx:

Maternal gene del 15q-
paternal gene silenced

Answer 19

Angelman syndrome

*microcephaly, ataxia, flapping movements, freq laughter (happy puppet)

Question 20

CGG repeats

Answer 20

Fragile X syndrome

*Neurobehav problems, prominent forehead, large protruding ears, long/narrow face, prominent chin, macroorchidism.

Question 21

AR mutation of ATP7B

Answer 21

Wilson disease
*hepatic copper accum&raquo_space; leark from damaged hepatocytes&raquo_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)

Question 22

CAG repeats expansion

Answer 22

Huntington disease (HD)
HTT gene

Question 23

Most common ataxia Dx

neurologic dysfx cardiomyopathy, DM

Answer 23

Friedreich ataxia

Question 24

X-linked MECP2 gene

Answer 24

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.

Question 25

X linked recessive
def HGPRT (hypoxanthine guanine phosphoribosyltransferase)

Answer 25

Lesch-Nyhan syndrome
incr uric acid
hypotonia, invol move (hand wrining)
*gout, self multilating behavior (lip/ finger biting)

Question 26

Lysosomal storach dz

Def in Beta-hexosaminidase (Hex A)

Answer 26

Tach Sachs dz
regression motor skill (2-6mo)
*macrocephaly
*cherry red spot on macula

Question 27

MECP2 gene mutation

• rare, Girls > boys
• onset: 6-18 mo

Answer 27

Rett syndrome
*sporadic, X chr
arrested brain dev (not neurodegen)
*initially normal dev&raquo_space; loss of speech, loss of purposeful hand use, sterotypical hand movement (wringing), gait abn, seizures, microcephaly