Genetic Disorders

Question 1

Cause of Cystic Fibrosis

Answer 1

Defect in Cystic fibrosis transmembrane conductance regulator (CFTR) protein

Question 2

Inheritance of Cystic Fibrosis

Answer 2

Autosomal recessive

Question 3

Defective CFTR protein results in ___

Answer 3

ABN Chloride secretion and l/t production of thick mucus

Question 4

Pulmonary Infections in Cystic Fibrosis

Answer 4

Psedumonas aeruginosa

Staph aureus

Question 5

Complications of thick mucus in Cystic Fibrosis

Answer 5

Bronchiectasis
Malnutrition
Pancreatic insufficiency
Diabetes mellitus 
CF-related liver dz

Question 6

Testing in Cystic Fibrosis

Answer 6

Sweat chloride

Genetic analysis of CFTR gene

Question 7

Tx of Colonized P. aerugnosa

Answer 7

Oral azithromycin

Inhaled tobramycin

Question 8

Down Syndrome

Answer 8

MC pattern of human malformation and cause of intellectually disability

Question 9

Etiology of Down Syndrome

Answer 9

Complete Trisomy 21 (95%)
Mosaic trisomy 21 (2.5%)
Robertsonian translocation, 21 to 14 (2.5%)

Question 10

Facial Features in Down Syndrome

Answer 10

Flattened nasal bridge
Low set ears
Prominent epicanthal folds
Brushfield spots (small spots on periphery of iris)
Slanted palpebral fissures

Question 11

Clinical Features in Down Syndrome

Answer 11

Global dev delay
Cognitive impairment
Hypotonia
50% congenital heart defects
Hypothyroidism
Hypogonadism
Atlantoaxial instability
Hip dysplasia

Question 12

Clinical Features of Fetal Alcohol Syndrome

Answer 12

Microcephaly
Thin vermillion border of upper lip
Smooth philtrum
Short palpebral features

Question 13

Floppy Baby Syndrome

Answer 13

Infant with low resistance to passive movement
Marked head lag
Floppy trunk, arms and legs
Delay in achieving gross motor milestones

Question 14

Fragile X Syndrome

Answer 14

MC form of inherited intellectual disability
MCC of autism
X-linked dominant
>200 CGC repeats

Question 15

Friedreich’s Ataxia

Answer 15

Progressive neuromuscular d/o

Question 16

Inheritance of Friedreich’s Ataxia

Answer 16

Autosomal recessive
Repeating fataxin gene on Chr 9
GAA repeats

Question 17

Absent Frataxin gene causes ___

Answer 17

Free iron accumulates in mitochondria producing oxidative stress that causes cell damage

Question 18

Friedreich’s Ataxia CF

Answer 18

Progressive ataxia
Sensory impairment
Loss of flexibility
Scoliosis
Hypertrophic cardiomyopathy
WC 5-15 years after onset
Dysarthria (ballistic pattern)
Dysphagia 
Diabetes

Question 19

EMG findings in Freidreich’s Ataxia

Answer 19

Absent sensory nerve action potentials (or of reduced amp)

Question 20

Hemophilia

Answer 20

Heritable d/o of blood coagulation caused by absence of key proteins required for clotting cascade

Question 21

Hemophilia inheritance

Answer 21

X-linked recessive A and B types

Question 22

Deficiency in Hemophilia

Answer 22

Factor VIII or IX

Question 23

Tx of Hemophilia

Answer 23

DDAVP (vasopressin) inc circulating levels of factor VII

Replacement of clotting factor

Question 24

Klippel-Feil Syndrome

Answer 24

Heterogenous collection of CF all unified by the presence of congenital synostosis of some or all cervical vertebrae

Question 25

Triad of Klippel-Feil Syndrome

Answer 25

Short neck Low hairline Limited cervical mobility in 50%

Question 26

Metachromatic Leukodystrophy

Answer 26

AR Lysosomal storage dz d/o with ABN myelin sheath

Question 27

Cause of Metachromatic Leukodystrophy

Answer 27

Deficiency of enzyme arylsulfatase A

Question 28

Mucopolysaccharidose Type 4

Answer 28

AR d/o d/t absence of/malfunction of lysosomal enzymes that breakdown glycosaminoglycan GAG

Question 29

Mucopolysaccharidose Type 4 CF

Answer 29

Skeletal changes Intellectual disabilities Involvement of viscera

Question 30

Neurofibromatosis

Answer 30

Common genetic d/o primary of peripheral nervous system that can cause neuro, behavior, cognitive, cardiovascular and MSK disabiliies

Question 31

Neurofibromatosis Inheritance

Answer 31

Autosomal dominant | NFI or NFII gene

Question 32

Neurofibromatosis CF

Answer 32

``` Limited ROM related to underlying plexiform NF Weakness, proximal Scoliosis Leg length discrepancy Pheochromocytoma possible ```

Question 33

Neurofibromatosis NIH criteria for DX

Answer 33

Two or more of the following - 6 or > café au lait spots - Axillary or inguinal fold freckling - One or more plexifom NF or 2 or > of any kind of NF - 2 or > Lishc nodules on slit lamp exam - Distinctive-related osseous lesion - 1st degree relative who meets above criteria

Question 34

Prader Willi syndrome

Answer 34

Multigenic d/o w/ hypotonia, obesity, resp difficulties and intellectual impairments

Question 35

Prader Willi syndrome inheitance

Answer 35

Loss of function of paternal gene group on Chr 1q11.2q13

Question 36

Prade Willi CF

Answer 36

``` Neonatal hypotonia, poor feeding, FTT Hyperphagia/obesity Hypogonadism and infertility Unusual nasal voice Skin picking Trichotillomania Low IQ ```

Question 37

Achondroplasia

Answer 37

MC form of dwarfism resulting in characteristically large head w/ frontal bossing and long narrow trunk w/ short limbs

Question 38

Achondroplasia inheritance

Answer 38

Autosomal dominant | Fibroblast growth factor receptor 3 gene (FGFR3)