Pediatric Conditions Flashcards
what is myotonic dystrophy? how many types?
progressive muscle wasting disease
DMI (typically more severe) -> Mild form/adult-onset AND congenital form (most severe)
DM2 (typically milder)
what’s the causes of DM1 and DM2 types of myotonic dystrophy?
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
what are the major features of DM1?
myotonia, cataracts, cardiac involvement
how many CTGs are there in the congenital form of DM1? childhood?
> 1000
50-1000
what are some of the health concerns with myotonic dystrophy?
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
how is myotonic dystrophy diagnosed?
EMG -> detect myotonia
DM1: PCR/southern
DM2: southern bloe
muscle biopsy not routine rec
clinical dx based on FHx and characteristic presentation
what % of those with congenital deafness have waardenburg syndrome?
1-3%
what gene is implicated in WS type 1?
PAX3
what are the major findings with WS1?
congenital sensorineural hearing loss (nonprogressive, bilateral, and profound)
white forelock/hair hypopigmentation
heterochromia
dystopia anthorum
affected 1st degree relative
what does WS1 need to be differentiated from?
other causes of SNHL and waardenburg syndrome types
what is the criteria for a clinical dx of WS1? how effective is sequencing?
2 major criteria; 1 major and 2 minor; identifying a PAX3 variant
seq detects >90% variants
del/dup detects about 6% of variants
how do we manage WS1?
audiology eval
hearing loss depends on severity
pregnancy management (folic acid)
protection form light of amelanotic regions
what gene is associated with Marfan syndrome? what % of cases are sporadic?
FBN1 (15q21.1)
25% sporadic
what are some of the common features of Marfan syndrome?
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
what are the dx criteria for Marfan syndrome called?
Ghent criteria
how do we dx Marfan syndrome?
sequencing of FBN1 not enough
combo of phsyical findings, imaging, seq, and FHx
how might we manage someone with Marfan syndrome?
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
What are some characteristics of DMD?
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
how many DMD cases are de novo vs. from carrier mother?
1/3 de novo
2/3 carrier mother
what gene is associated with Duchenne Muscular Dystrophy? molecular etiology?
located on X chromosome
deletion of one or more exons (65%)
duplication of exons (6-10%)
small mutations or rearrangements (25%)
how can we dx DMD?
CK, cytogenetics, molecular analysis of DMD gene, ECH, radiography, pulmonary function testing, muscle biopsy
how can we manage DMD?
corticosteroids, exon-skipping drugs, PT, assistive devices/mobility, surgical interventions, monitoring of pulmonary and cardiac function
what % of individuals with CF are homozygous for delta-F508? compound het?
50% delta-F508
40% compound het
what’s the carrier frequency for CF in NHWs?
1:25
what systems are mostly impacted by CF?
respiratory, digestive, and reproductive
what’s the average lifespan?
47.7y
how do we dx CF?
sweat chloride test is gold standard (at least 60mmol/L)
NC NBS (two tiered immunoreactive trypsiongen/DNA process
what are some early indications of CF?
- salty sweat
- FTT
- constant coughing and wheezing
- thick mucus or phlegm
- greasy, smelly stools that are bulky and pale colored
how many variants are included on the ACMG recommended carrier screening panel?
who does NSGC recommend carrier testing for?
23
all women of reproductive age
what common features are there with oculocutaneous albinism type 1?
fair skin, white or light hair
reduced pigmentation of iris and retina -> decreased vision sharpness
what inheritance pattern doe OCA1 follow? how are the types different?
AR
type A -> causes a lack of pigmentation
B -> limits melanin production
how many subtypes and genes?
7 subtypes
1: TYR
2: OCA2
3: TYRP1
4: SLC45A2
5-7: rare and poorly characterized
