Pediatric Conditions

Question 1

what is myotonic dystrophy? how many types?

Answer 1

progressive muscle wasting disease

DMI (typically more severe) -> Mild form/adult-onset AND congenital form (most severe)

DM2 (typically milder)

Question 2

what’s the causes of DM1 and DM2 types of myotonic dystrophy?

Answer 2

DM1: AD, DMPK (19q13.3) -> intracellular signaling; CTG trinuc repeat; anticipation and reverse anticipation; somatic instability

DM2: AD, CNBP (3q21.3) -> reg of other genes; CCTG tetranuc repeat; no anticipation; somatic instability

Question 3

what are the major features of DM1?

Answer 3

myotonia, cataracts, cardiac involvement

Question 4

how many CTGs are there in the congenital form of DM1? childhood?

Answer 4

> 1000

50-1000

Question 5

what are some of the health concerns with myotonic dystrophy?

Answer 5

sleep apnea

hair/skin/nails: frontal balding

cataracts

cardio conduction disease

diabetes

IBS and cholelithiasis

fertility problems

main causes of fertility: respiratory or cardiac complications

Question 6

how is myotonic dystrophy diagnosed?

Answer 6

EMG -> detect myotonia

DM1: PCR/southern

DM2: southern bloe

muscle biopsy not routine rec

clinical dx based on FHx and characteristic presentation

Question 7

what % of those with congenital deafness have waardenburg syndrome?

Answer 7

1-3%

Question 8

what gene is implicated in WS type 1?

Answer 8

PAX3

Question 9

what are the major findings with WS1?

Answer 9

congenital sensorineural hearing loss (nonprogressive, bilateral, and profound)

white forelock/hair hypopigmentation

heterochromia

dystopia anthorum

affected 1st degree relative

Question 10

what does WS1 need to be differentiated from?

Answer 10

other causes of SNHL and waardenburg syndrome types

Question 11

what is the criteria for a clinical dx of WS1? how effective is sequencing?

Answer 11

2 major criteria; 1 major and 2 minor; identifying a PAX3 variant

seq detects >90% variants

del/dup detects about 6% of variants

Question 12

how do we manage WS1?

Answer 12

audiology eval

hearing loss depends on severity

pregnancy management (folic acid)

protection form light of amelanotic regions

Question 13

what gene is associated with Marfan syndrome? what % of cases are sporadic?

Answer 13

FBN1 (15q21.1)

25% sporadic

Question 14

what are some of the common features of Marfan syndrome?

Answer 14

skeletal: overgrowth of long bones and legs; scoliosis; pectus excavatum
ocular: dislocation of lenses, nearsightedness
cardio: aortic dilation, aortic and mitral regurgitation, mitral valve prolapse

Question 15

what are the dx criteria for Marfan syndrome called?

Answer 15

Ghent criteria

Question 16

how do we dx Marfan syndrome?

Answer 16

sequencing of FBN1 not enough

combo of phsyical findings, imaging, seq, and FHx

Question 17

how might we manage someone with Marfan syndrome?

Answer 17

medication to slow aortic root dilation nad dissection

surgery: repair significantly dilated or dissected aortic root; repair of pectus deformity; removal of dislocated lens or restoration of detached retina

scoliosis can be managed

hormonal therapy may be used to restrict growth

Question 18

What are some characteristics of DMD?

Answer 18

progressive muscle weakness and deterioration

onset in early childhood (4-5years) -> motor delays, waddling gait, Gower’s sign, hypertrophic calf muscles

inability to walk usually before 13y (scoliosis/lordosis and contractures)

more serious outcomes as muscles deteriorate

Question 19

how many DMD cases are de novo vs. from carrier mother?

Answer 19

1/3 de novo

2/3 carrier mother

Question 20

what gene is associated with Duchenne Muscular Dystrophy? molecular etiology?

Answer 20

located on X chromosome

deletion of one or more exons (65%)
duplication of exons (6-10%)
small mutations or rearrangements (25%)

Question 21

how can we dx DMD?

Answer 21

CK, cytogenetics, molecular analysis of DMD gene, ECH, radiography, pulmonary function testing, muscle biopsy

Question 22

how can we manage DMD?

Answer 22

corticosteroids, exon-skipping drugs, PT, assistive devices/mobility, surgical interventions, monitoring of pulmonary and cardiac function

Question 23

what % of individuals with CF are homozygous for delta-F508? compound het?

Answer 23

50% delta-F508

40% compound het

Question 24

what’s the carrier frequency for CF in NHWs?

Answer 24

1:25

Question 25

what systems are mostly impacted by CF?

Answer 25

respiratory, digestive, and reproductive

Question 26

what’s the average lifespan?

Answer 26

47.7y

Question 27

how do we dx CF?

Answer 27

sweat chloride test is gold standard (at least 60mmol/L)

NC NBS (two tiered immunoreactive trypsiongen/DNA process

Question 28

what are some early indications of CF?

Answer 28

• salty sweat
• FTT
• constant coughing and wheezing
• thick mucus or phlegm
• greasy, smelly stools that are bulky and pale colored

Question 29

how many variants are included on the ACMG recommended carrier screening panel?

who does NSGC recommend carrier testing for?

Answer 29

23

all women of reproductive age

Question 30

what common features are there with oculocutaneous albinism type 1?

Answer 30

fair skin, white or light hair

reduced pigmentation of iris and retina -> decreased vision sharpness

Question 31

what inheritance pattern doe OCA1 follow? how are the types different?

Answer 31

AR

type A -> causes a lack of pigmentation

B -> limits melanin production

Question 32

how many subtypes and genes?

Answer 32

7 subtypes

1: TYR
2: OCA2
3: TYRP1
4: SLC45A2
5-7: rare and poorly characterized