Diseases

Question 1

Trisomy 13

Answer 1

47,XX or XY, +13
Patau’s Syndrome
holoprosencephaly: central cleft palate, brain anomalies, ventricular dilatation
microcephaly, facial anomalies, small, low-set ears, polydactyly, cardiac defects hypoplastic left heart echogenic intracardiac focus, renal anomalies, clenched fists, severe intellectual disability, omphalocele, single umbilical artery, club feet

Question 2

Trisomy 21

Answer 2

47,XX or XY, +21
Down Syndrome
flat facies, upturned palpebra fissures, microphthalmia, clinodactyly, sandal gap deformity, single palmer creases, hypotonia, microcephaly, brushfield spots

Question 3

cri du chat

Answer 3

46,XY or XX, del(5p)
Mewing, cat-like cry, microcephaly, hypertelorism, epicanthal folds, low-set ears, pre-auricular tags, micro retrognathia, poor feeding

Question 4

Klinefelter syndrome

Answer 4

47, XXY
Male, tall, underdeveloped secondary sexual characteristics, gynecomastia, language difficulties

Question 5

Turner Syndrome

Answer 5

45,X0
female, short, webbed neck, lymphedema, broad chest with widely spaced nipples, cubitus valgus, hearing loss, edema of hands and feet, cardiac anomalies (aortic valve, coarctation of aorta), renal abnormalities, ovarian failure, delayed puberty, learning disability

Question 6

22q11.2 syndrome

Answer 6

DiGeorge syndrome
46, XX, del(22)(q11q11)
conotruncal cardiac anomalies (truncus arteriosus, tetralogy of Fallot, interrupted aortic arch), hypoplastic thymus (immunodeficiency), hypocalcemia, variable craniofacial abnormalities (high arched palate, retrognathia, long face with prominent nose, hypertelorism low-set ears, smooth philtrum), hypernasal speech, intellectual disability

Question 7

Cystic Fibrosis

Answer 7

mutation in CFTR gene
sx: clubbing, URI, malodorous diarrhea, cough, diffuse rhonchi, small stature, sweat chloride test is >40 mmol/L

Question 8

Neurofibromatosis 1

Answer 8

autosomal dominant, age-dependent penetrance
2 or more sx: cafe au lait spots (>6, at least 5 mm in diameter if pre-pubertal or 15 mm if post-pubertal), >2 lisch nodules, 2 or more neurofibromas or 1 plexiform neurofibroma, axillary or inguinal freckling, optic glioma, distinctive bony lesion (ex. sphenoid dysplasia), 1st-degree relative with the disorder

Question 9

Duchenne muscular dystrophy

Answer 9

lack of dystrophin protein os muscle is replaced with connective tissue and fat
sx: + gowers sign, waddling gait, serum CK 50x higher than normal, muscle biopsy immunostaining dark

Question 10

Rett Syndrome

Answer 10

mutation in MECP2 gene in X chromosome
only girls affected because males die in utero
no sx for first 18 months
sx: ringing, midling hand movements, spasticity, decelerating head growth, loss of language and motor skills

Question 11

Marfan’s syndrome

Answer 11

autosomal dominant, mutation of FBN1 gene
sx: longer limbs and fingers, pectus excavatum/carinatum, high, arched palate, aortic dissection, mitral valve prolapse, pneumothorax, extreme nearsightedness

Question 12

Prader willi syndrome

Answer 12

loss of expression in paternal gene material in 15q11&13 resulting in maternal imprinting
sx - hypotonia, obesity at young age, behavioral issues, almond eyes, smaller forehead, triangle shaped mouth

Question 13

Angelman syndrome

Answer 13

cause of expression of maternal gene resulting of paternal imprinting of 15q11&13
sx: ataxia, intellectual disability, happy demeanor, seizures, hand flapping

Question 14

Fragile X

Answer 14

X-linked dominant
defect in number of repetitive CGG trinucleotide repeats (55-200 repeats - premutation, no symptoms unless male, put females at risk for ovarian failure; >200 repeats - express phenotype, 40-50% in females because of X inactivation)
sx: long face, ears, intellectual disability
most common inheritable intellectual disability

Question 15

Huntington’s disease

Answer 15

mutation in HTT gene resulting in increased CAG nucleotide repeats (10-35 normal; 36-39 sx may or may not develop; >40 will develop disorders)
symptoms appear in middle aged pts

Question 16

Beta Thalassemia (types, sx, findings)

Answer 16

AKA Cooley’s Anemia
Minor (trait) 1/4 missing allele - silent to mild clinical severity
intermediate - non-transfusion dependent
major - more than 1/2 alleles missing - transfusion-dependent
sx - microcytic anemia fatigue, dyspnea, jaundice, icterus, sx not seen until after few months of life due to not being part of fetal hemoglobin
findings: inc HgbA2 >3%, hypochromic microcytic RBC’s, target cells, anisopoikilocytosis, mentzer index < 13, extramedullary hematopoiesis (chipmunk face), osteopenia, hepatosplenomegaly

Question 17

Alpha Thalassemia (sx, findings)

Answer 17

sx - hydrops fetalis (Hb Barts) microcytic anemia, fatigue, dyspnea, jaundice, scleral icterus
findings: hypochromic microcytic RBC’s, Target Cells, Anisopoikilocytosis, Mentzer Index < 13, hepatosplenomegaly, extramedullary hematopoiesis, osteopenia

Question 18

Sickle Cell Disease (molecular cause, effect, triggers, effect on pt, inheritance)

Answer 18

point mutation in beta-globulin gene: HgbS -> Glu to Val in protein 6 (Glu6Val)
effect of mutation - missense, change in AA causes Hgb to polymerize, RBC takes a sickle shape
triggers - low O2, dehydration, infection
effects - sickle shape causes vaso-occlusion, hemolysis of RBC, jaundice, scleral icterus
autosomal recessive, heterozygotes - sickle cell trait (SCT)

Question 19

Laminopathies

Answer 19

LMNA gene codes for Lamin A and C.
diseases caused - hutchinson-gilford progeria, emery-dreifuss muscular dystrophy (EDMD), dilated cardiomyopathy, familial partial lipodystrophy of the Dunnigan-type (FPLD), Charcot-Marie-Tooth disorder type 2 (CMT2B1)
classic phenotype heterogeneity

Question 20

Bloom Syndrome

Answer 20

helicase disorder
autosomal recessive
BLM gene mutations (a RecQ DNA helicase)
sx - short stature, skin rash after sun exposure, greatly increased cancer risk, can’t get any ionizing radiation tests done

Question 21

Werner Syndrome

Answer 21

helicase disorder
autosomal recessive
WRN gene mutation (RecQ DNA helicase)
sx- nl growth until puberty, then growth stops, adults are short in stature, premature aging: in 20s-30s, pts develop conditions associated with older age and have increased cancer risk

Question 22

Xeroderma Pigmentosum

Answer 22

Mutations in NER genes (XPC, XPA, and XPV)
acute sensitivity with marked freckle-like pigmentation of the face before 2 years old
photophobia, severe keratitis, atrophy of the skin of the lids, ocular surface neoplasms, risk for skin cancers within first decade of life. approx 25% of affected individuals have neurologic manifestations
most common causes of death - skin cancer, neurologic degeneration, and internal cancer

Question 23

Ataxia Telangiectasia

Answer 23

mutation in ATM gene (non-homologous end joining DNA repair)
autosomal recessive
sx - progressive cerebellar ataxia beginning bt 1-4 yrs. oculomotor apraxia, choreoathetosis, telangiectasias of the conjunctiva and skin, immunodeficiency, frequent infections, and an increased risk for malignancy - leukemia and lymphoma

Question 24

I-cell disease (inclusion cell disease/ mucolipidosis type III)

Answer 24

autosomal recessive lysosomal storage disorder, defect in GNPTA gene
-results in failure of the golgi to phosphorylate mannose-6-phosphate on glycoproteins
-secreted extracellularly rather than delivered to lysosomes
- sx - coarse facial features, gingival hyperplasia, clouded corneas, restricted joint movements, claw hand deformities, kyphoscoliosis, and high plasma levels of lysosomal enzymes