Genetic disorders/Diseases

Question 1

Huntington’s disease

Answer 1

• Trinucleotide repeats is used to diagnose HD
• HD gene is on short arm of chromosome 4

Question 2

Wilson’s disease

Answer 2

• Low serum ceruloplasmin

Question 3

Acute intermittent porphyria

Answer 3

Excessive amounts of urine prphobilinogens and aminolevulinic acide in urine
- Presents as abdominal pain, tachycardia, tingling in hands and feet, paranoia and hallucinaitons

Question 4

Lambert-eaton myasthenic syndrome

Answer 4

paraneoplastic abnormality of PREsynaptic acetylcholine release, often described in conjunction with small-cell lung carcinoma
- likely immune mediated against voltage gated calcium channels on the presynaptic side of the nueromuscular junction
- generalized weakness with initial improvement after minimal exercise

Question 5

Guillain Barre syndrome

Answer 5

acute inflammatory demyelinating polyneuropathy (AIDP) is a rapidly occurring demyelinating disease that can present with ascending pain, paralysis
- loss of deep tendon reflexes in the extremities
- tests of choice EMG and nerve conduction studies which reveal loss of H reflex and decreased nerve conduction velocities

Question 6

Polymyositis

Answer 6

Inflammatory disease of the muscle

Question 7

Tuberous sclerosis

Answer 7

• Autosomal dominant
• Nuerocutaneous disorder with a prevalence of about 1 in 6000-9000 individuals
• seizures, mental retardation
• cutaneous lesions include: ash leaf spot (hypomelanotic macule), adenoma sebaceum (facial angiofibromas), shagreen spots (irregularly shaped often raided or textures skin lesions on the back or flank), retinal haratomas
• neuropathologic lesions inlcude: subependymal nodules and cortical hamartomas

Question 8

Rett’s disorder

Answer 8

Pervasive developmental disorder only seen in girls, involves deceleration of head growth from ages 5 months to 4 years, loss of purposeful hand skills and development of stereotyped hand movements between 5 months and 2.5 years, loss of social engagement and acquired impairment in expressive and receptive language skills, seizures observed in up to 75% of patients

Question 9

NF 1

Answer 9

• Cafe-au-lait spots, subcutaneous neurofibromas, axillary freckling, lisch nodules (pigmented iris hamartomas), optic nerve gliomas, neurofibroms, and schwannomas.
• caused by a mutation of NF1 gene on chromosome 17

Question 10

NF2

Answer 10

• Chromosome 22
• bilateral vestibular (nerve 8) schwannomas

Question 11

Williams

Answer 11

-AD
-mental retardation
- hemizygous deletion that includes the elastin locus on chromosome 7q11-q23.
- short stature, depressed nasal bridge, broad forehead, widely spaced teeth, elphin like facies
- thyroid, renal and cardiovasacualr abnormalities
- anxiety, hyperactivity, hypermusicality

Question 12

What chromosomes are associated with Alzheimers

Answer 12

long arm of 21 (gene for amyloid precursor protein) and 19 (apo E4 gene)

Question 13

Turners syndrome

Answer 13

female but with no secondary sex characteristics and an absence or minimal development of gonads
- one x chromosome

Question 14

klinefelters syndrome

Answer 14

presence of an extra chromosome, xxy
-male habitus but do not develop strong male characteristics
-small, underdeveloped genitals, infertile and can develop breast tissue

Question 15

What is myasthenia gravis?

Answer 15

Autoimmune neurologic disorder involving the production of autoantibodies against postsynaptic nicotinic acetylcholinergic receptor sites on muscle
- offending antibodies cross placenta to fetus
- clinical features: diplopia, dysarthria, bulbar palsy, fatigue and muscle weakness
- deep tendon reflexes are preserved
- relationship between MG and thymoma- 10% of pts with MG have thymoma
- Edrphonium chloride is a short acting cholinergic agent used to diagnose the disorder clinically, other diagnostic tests include EMG and nerve conduction studies (decreased amplitude on repetitive stimulation), titer of serum antibodies
- Pyrostigmine is used to treat the disorder on an ongoing basis, can also use steriods, plasmapharesis, IVIG, immunosupressive agents such as azathioprine

Question 16

Duchenne’s muscular dystrophy

Answer 16

-X linked recessive
- due to lack of muscle dystrophin (a protein found in muscle membrane)
- muscle weakness greater proximally
- Diminished DTR, elevated CPK, mental retardation (1/3 of cases), enlarged muscles due to fat infiltration

Question 17

SIADH vs. psychogenic polydipsia vs. diabetes insipidus

Answer 17

SIADH: Urine output decreases, more concentrated, sodium goes down
Psychogenic polydipsia: Urine output increases, less concentrated, sodium goes down
Diabetes insipidus: urine output goes up, urine is less concentrated, sodium increases

Question 18

What are short palpebral fissures seen in?

Answer 18

Fetal alcohol syndrome

Question 19

Fragile X syndrome

Answer 19

• mental retardation
• long ears
• marrow face
• short stature
• hyperextendable joints
• arched palate
• macro-orchidism
• seizures
• autistic features
• coincides with high rate of ADHD and learning disorders
• second most common cause of mental retardation
• It is the result of mutation of the X chromosome
  X linked dominant *

Question 20

What age would you expect child to tolerate mother’s absence without distress?

Answer 20

25 months

Question 21

Wilson’s disease

Answer 21

Autosomal recessive
abnormal copper metabolism-problem with incorporation of copper into ceruloplasmin and with diminished biliary excretion of copper
- excessive copper in brain-basal ganglia
- decreased cerulopasmin
clinical: parkinsonism, flapping tremor, ataxia, dystonia, bulbar signs-dysphagia and dysarthria, signs of liver failure usually present
Linked to chromosome 13
Treatment: pencillamine-copper chelating agent- can reverse deficits of disease in many cases

Question 22

Metachromatic leukodystrophy

Answer 22

• Autosomal recessive
• Metabolic disorder of myelin that results in deficiency of arylsulfatase A (ASA) leading to abnormal accumulation of sulfatides in the brain and peripheral nerves leading to progressive demyelination
• gene is located on chromosome 22q13
  Clinical presentation infantile/juvenile: gait disorder w/ hypotonia and lower limb areflexia often proceed CNS involvement
  Adult onset: tends to present with progressive dementia and behavioral problems
  Both have delayed nerve conduction velocities

Question 23

Tay-sachs disease

Answer 23

-autosomal recessive
- severe infantile form of the autosomal recessive gangliosidosis
- hexosaminidase A deficiency
- retardation, paralysis, dementia, blindness and death in year 2-3
- cherry red spot on fundoscope
- hyperreactive startle response

Question 24

Lesch-nyhan syndrome

Answer 24

X linked recessive hereditary disorder of purine and pyrimidine metabolism. hyperuricemia results from a deficiency in hypoxanthine-guanine phsphoribosyltransferase
- choreoathetosis, hyperreflexia, hypertonia, dyarthria, behavioral distrurbances, cognitive impairment and self-mutilation

Question 25

Gaucher’s disease

Answer 25

• autosomal recessive resulting from B-glucosidase deficiency
  Type 1: hematologic anomalies, hypersplenism, bone lesions, skin pigmentation, ocular pingueculae

Question 26

sturge-weber

Answer 26

neurocutaneous disorder that is sporadic and not genetically inherited
- facial cutaneous angioma usually with a brain angioma ipsilateral to the skin lesion.
- contralateral hemiparesis, mental retardation, homonymous hemianopia, seizures. Glucoma is common and if untreated can lead to blindness

Question 27

Von hippel lindau syndrome

Answer 27

-autosomal dominat
-retinal and CNS hemangioblastomas (cerbellum mostly) and visceral cysts and tumors (renal cysts), can have pheochromocytomas

Question 28

Ataxia Telangiectasia

Answer 28

Autosomal recessive
-ataxia in childhood then telangeictases (earlobes, nose, sclerae), higher risk for lymphoma and leukemia, abnormal eye movements

Question 29

Fabry’s disease

Answer 29

X-linked lysosomal storage disease
-deficiency in alpha galactosidase A
- asymptomatic red or purple papules around the umbilicus hips thighs and scrotum
corneal deposits
painful dysesthesias of distal extremities, cerebral thrombosis or hemorrhage and vascular narrowing
renal failure common cause of death

Question 30

Friedrich’s ataxia

Answer 30

autosomal recessive on chromosome 9, expansion of GAA
- gait ataxia, loss of lower extremity proprioception and absence of DTR
- dysarthria, babinski sign, eye movement abnoramlites
- death of often due to hypertrophic cardiomyopathy in 40s

Question 31

Myotonic dystrophy

Answer 31

autosomal dominant trinucleotide repeat ctg on 19
ptosis, bifacial weakness, frontal baldness, triangular drooping faces, motor weakness greater distally
- myotonia- unable to let go hand shake
- fibrotic or inflitrative cardiomyopathy
- PCR is diagnostic
EMG: myopahtic features and myotonic discharges
perifascicular muscle atrophy on histo

Question 32

trimsomy 18

Answer 32

50% dont live past first week of life
- low set ears, small jaw, hypoplastic fignernails, MR, cryptorchidism, congenital heart defect, microcephaly, renal abnormalities

Question 33

cri-du-chat

Answer 33

deletion short arm of chromosome 5
- MR, microcephaly, cat like high pitched cry, do not live past early childhood

Question 34

Prader-willi syndrome

Answer 34

Autosomal dominant disorder
15q11-q13
- high caloric intake-diabetes cardiac failure

Question 35

trinucliotide repeat diseases

Answer 35

fragile x
myotonic dystrophy
huntingtons
x-linked spinobulbar muscular atrophy
dentatorubral-pallidoluysian atrophy
spinocerebellar atrophies
fredricks ataxia

Question 36

Klinefelter’s syndrome

Answer 36

xxy
- small dysfunctional testes
- MR
- pear shaped stature

Question 37

turner’s syndrome

Answer 37

• absence of x chromosome in genetic female (XO)
• short stature and lack of pubertal sexual development
• webbed neck and heart and kidney anomalies

Question 38

prader willi syndrome

Answer 38

deletion on the paternal chromosome 15
-MR, hypogonadism, hypotonia, behavior disinhibition, rapid and excessive weight gain and facial dysmorphism

Question 39

Mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes (MELAS)

Answer 39

most common mitochondrial disorder
- stroke like episodes
- onset childhood or early adult life

Question 40

Myoclonus epilepsy with ragged-red fibers (MERRF)

Answer 40

• childhood or early adulthood
• myoclonic seizures in childhood, ataxia and mental retardation

Question 41

leber’s hereditary optic neuropathy (LHON)

Answer 41

isolated bilateral optic neuropathy
usually males
15-35
painless and central vision loss in one eye then the other

Question 42

Kearns–Sayre syndrome (KSS)

Answer 42

-progressive external opthalmoplegia
-onset before 20
-short stature, pigmentary retinopathy, cerebellar ataxia, heart block and elevated CSF