Gen Path Final Exam Section 6: Genetic and Pediatric Disease Flashcards
genome
organism’s genetic material
gene
set of nucleotides; is basic unit of inheritance; and instructs protein synthesis, which influences phenotype
Allele
alternative form of a gene; single gene locus
Diploid = paired alleles
Hereditary
transmitted to offspring
Perinatal
last trimester and 1st month after birth
Neonate
first 4 weeks (“newborn”)
Infant
1st year after birth
Congential
present at birth (unrelated to inheritance)
What are the three Mendelian Disorder categories?
- Autosomal Dominant (1-22 chromosomes)
- Autosomal Recessive (1-22 chromosomes)
- X-linked Recessive (23 chromosome)
What are features of Autosomal Dominant Disorders?
- manifest in heterozygous state
- sporadic mutations possible (no family history)
- Reduced Penetrance
- Variable Expressitivity
- Delayed age onset
What do Autosomal Dominant disorders effect?
- structural proteins
2. membrane receptors
What is reduced penetrance?
inherit mutated gene but DO NOT ever manifest with condition
What is Variable Expressitivity?
different people with same mutant gene manifest with widely-variable clinical features
What does delated age onset mean?
may not notice in infancy; but manifests later childhood, adolescence, or young adulthood
What are features of Autosomal Recessive Disorders?
- manifest in homozygous state
- Complete penetrance
- early onset (shortly after birth)
- rarely sporadic
What does Autosomal Recessive Disorders effect?
enzymatic proteins –> result in abnormal metabolic processes
What is complete penetrance?
expressed completely in individuals affected by such conditions
What are features of X-linked Recessive disorders?
- sex-linked = allosomal (irregularities on 23rd chromosome)
- All are X-linked (females are protected; males are prime targets)
What is the offspring chance of having an X-linked disorder with a heterozygous mother?
heterozygous females = asymptomatic “carriers” and the male offspring have 50% chance manifesting with the disorder
What is the relationship between hereditary disorders and congenital disorders?
NOT all hereditary disorders are congenital
AND
NOT all congenital disorders are hereditary
What is autosomal dominant condition of the FBN1 gene and what does affect?
Marfan Syndrome; causes Fibrillin to be abnormal
What is Fibrillin?
- structural protein
- in microfibrils of ECM
- abdundant in many CT, esp. tissues highly elastic
(ass. w/ Marfan Syndrome)
What tissues is Marfan Syndrome MC manifest in?
- osseous skeleton tissues
- eyes
- cardiovascular tissue
What percentage of cases of Marfan Syndrome are inherited? Sporadic? And how many people are affected?
85% inherited (familial)
15% results of new FBN1 gene mutations (sporatic)
~1 per 5,000
What the clinical features of Marfan Syndrome?
- overgrowth of many long bones
- elongated head/face (dolichoecephaly)
- long hands/fingers (arachnodactyly)
- 1.05 or greater of arm length/ height
- sternal abnormalities (pectus carinatum or excavatum)
- long arms
- long feet/toes
- high-arched palates
- positive Steinburg sign or Wrist sign
- Pes planovalgus
- Scoliosis
- Protrusio acetabuli
- Ectopia lentis
- cardiovascular complications
- dural ectasia
What are Ectopia lentis, cardiovascular complications, and dural ectasia features of?
Marfan Syndrome
What is an autosomal dominant OR autosomal recessive disoder that affects collagen protein synthesis?
Ehlers-Danlos syndrome
abnormal collagen lacks tensile strength
What tissues are rich in collagen, therefore MC affected by Ehlers-Danlos syndrome?
joint cartilage, skin, and ligaments
What are clinical features of Ehlers-Danlos syndrome?
- tissues distend (risk of tissue injury)
- joint hypermobility (dislocations)
- hyperextensible skin
- vulnerable to visceral trauma (injury to colon or large arteries or hiatal hernias)
- vascular fragility (therefore, poor wound healing)
What disorder is autosomal dominant and is a loss-of-function mutation in LDLR gene?
Familial Hypercholesterolemia
- affects ~1 in 500 inds. in US
What does the LDLR gene do? and if altered what happens?
- regulates LDL receptors
- mutations impair translocation and breakdown (catabolism) of LDL cholesterols
- is a membrane receptor disease
(ass. w/ Familial Hypercholesterolemia)
What are clinical features of Familial Hypercholesterolemia?
- increase levels of LDL cholesterols = hypercholesterolemia
- encourages premature atherosclerotic plaques
- may cause coronary disease and increase risk of lethal myocardial infarctions
Heterozygous individuals with Familial Hyperhcolesterolemia
- have elevated LDL levels ~2-3x normal
- manifest with Xanthomas or coronary artery disease in early adulthood
Homozygous individuals with Familial Hypercholesterolemia
- have elevated LDL levels ~5x normal
- more serious and life-threatening presentation
- develop Xanthomas during childhood and commonly die from lethal myocardial infarction
What is an autosomal recessive disorder that has mutations in CFTR gene?
Cystic Fibrosis
- affects ~ 1 in 3,000 caucasians