General genetics / metabolic 2 Flashcards
Long QT syndrome
features
gene(s)
inheritance
- defects in ion channel signaling; leads to syncope, palpitations; onset usually in childhood
- KCNQ1, KCNH2
- AD inheritance
Arrhythmogenic right ventricular cardiomyopathy
features
gene(s)
inheritance
- fibrofatty replacement of cardiac cells; leads to syncope, palpitations, sudden death; onset ~40y
- PKP2; DSG2; DSP
- AD inheritance
Hypertrophic cardiomyopathy
features
gene(s)
inheritance
- thickening of (often left) ventricle; leads to shortness of breath, dizziness, syncope, palpitations, increased stiffness, sudden death; onset 15-35y
- MYH7, MYBPC3
- AD inheritance
Cornelia de Lange syndrome
features
gene(s)
inheritance
- distinctive facial features; growth retardation; hirsuitism; upper limb reduction defects; severe ID
- NIPBL, SMC1A, SMC3 genes
- NIPBL/SMC3: AD inheritance; SMC1A: XL inheritance
Cat-eye syndrome
features
gene(s)
- iris coloboma; kidney abnormalities
- 22q tetraploidy
PKU
features
gene(s)
inheritance
- ID develops throughout childhood w/o restricted diet
- PAH gene
- AR inheritance
MSUD
features
gene(s)
inheritance
- severe symptoms onset days after birth; diet restriction leads to favorable outcomes
- BCKDHA, BCKDHB, DBT genes
- AR inheritance
Wilson disease
features
gene(s)
inheritance
- copper metabolism disorder; hepatic, neurologic, psychiatric features onset age 3-50+
- ATP7B gene
- AR inheritance
Menkes syndrome
features
gene(s)
inheritance
- defect in copper transport
- normal development until age 2-3m –> loss of milestones –> neurologic and hair texture changes –> death by age 3y
- ATP7A gene
- XLR inheritance
Methylmalonic acidemia
features
gene(s)
inheritance
- severe symptoms onset neonatally or in infancy
- MUT, MMAA, MMAB, MCEE, MMADHC genes
- AR inheritance
Glutaric acidemia
features
gene(s)
inheritence
- severe symptoms onset usually in infancy; macrocephaly
- GCDH gene
- AR inheritance
Charcot-Marie-Tooth disease
features
gene(s)
inheritance
- inherited peripheral neuropathies
- many genes and all inheritance types
- -PMP22 gene duplication leads to CMT1A which is AD
- -PMP22 gene deletion leads to HNPP which is AD
- -GJB1 gene mutation leads to CMT1X which is XL
Huntington’s disease
features
gene(s)
inheritance
- motor deficits; loss of voluntary movement; cognitive challenges; psychiatric symptoms
- HTT gene repeat expansion
- AD inheritance
Crouzon syndrome
features
gene(s)
inheritance
- normal intellect and extremeties; craniofacial (proptosis, strabismus, mandibular prognathism)
- FGFR2 gene
- AD inheritance
What are the FGFR-related craniosynostosis syndromes?
- Pfeiffer
- Apert
- Crouzon
- Beare-Stevenson
- FGFR2-related isolated coronal synostosis
- Jackson-Weiss
- Crouzon w/acanthosis nigricans
- Muenke
Saethre-Chotzen
features
gene(s)
inheritance
- coronal synostosis; facial asymmetry; sometimes 2-3 syndactyly
- TWIST1 gene
- AD inhertiance
22q11.2 deletion
features
gene(s)
inheritance
- CHD; palatal abnormalities; characteristic facies; learning difficulties; immune deficiency
- contiguous gene deletion at 22q11.2
- AD inheritance
McCune Albright
features
gene(s)
inheritance
- bone, skin (irregular CALMs), endocrine findings; female menstrual bleeding by age 2; gigantism
- GNAS1 gene gain-of-function mutations
- mosaic; not inherited
Which chromosome abnormality does not have a maternal age effect?
Turner syndrome
What usually causes 45,X?
an error in paternal meiosis
What type of metabolic disorders have normal urinalysis?
fatty acid oxidation
Noonan syndrome
features
gene(s)
inheritance
- characteristic facies; cardiovascular findings; skin findings; DD
- several genes; half PTPN11
- AD inheritance
Name the 9 RASopathies:
- NF1
- Cap-AV malformation
- Costello
- Legius
- ALPS
- cardio-facio-cutaneous
- Noonan
- LEOPARD
- gingival fibromatosis 1
Congenital Adrenal Hyperplasia (CAH)
features
gene(s)
inheritance
- 3 types; all with female internal genitalia and precocious puberty / dexamethasone therapy during pregnancy may prevent effects
- CYP21A2 gene
- AR inheritance (carrier freq. 1/55)
Name 6 syndromes with ambiguous genitalia:
- CAH
- Camptomelic dysplasia
- SLOS
- WAGR
- Denys-Drash syndrome
- Frasier syndrome
meningocele
meninges of spinal cord herniate through an opening
myelomeningocele
failure of primary neurulation leading to both meninges and spinal cord herniating through vertebral defect
*often associated with hydrocephalus
exencephaly
skull and scalp are absent
encephalocele
herniation of cranial contents through skull defect
iniencephaly
face facing up