PATH FINAL - Part 2 (Section 6 & 7)

What is the term for a set of nucleotides?

gene

What is the term for an alternative form of a gene?

allele

What is the term for genetic makeup of an organism?

genotype

What is the term for observable characteristics resulting from a genotype?

phenotype

What is heterozygous?

each allele is different, Yy

What is homozygous?

each allele is the same, YY

T/F? All hereditary disorders are congenital

False - not all present at birth

1 gene coding for an abnormal trait describes what kind of disorders?

Single-Gene (Mendelian) Disorders

What are the 2 key unique aspects of autosomal dominant disorders?**

altered structural proteins and membrane receptors

Familial hypocholesterolemia is an example of what kind of disorder?

Mendelian

T/F? A patient can develop a autosomal dominant mutation with no family history

True - only takes 1 random mutation

With autosomal dominant disorders, each child has a _____% chance of expression

50% chance

(1 affected parent)

T/F? Autosomal dominant disorders have an early onset

False - delayed onset (unique aspect)

In autosomal dominant disorders, what is reduced penetrance?

have mutation, but phenotypically normal (no manifestation of disease)

In autosomal dominant disorders, what is variable expressivity?

same mutation expressed differently in different individuals

What is the key unique aspect of autosomal recessive disorders?

altered enzymes

What are the MOST common group of Mendelian disorders?

autosomal recessive disorders

T/F? Autosomal recessive disorders affect males and females equally

True

With autosomal recessive disorders, each child has a _____% chance of expression

25%

T/F? Autosomal recessive disorders have early onset

True - early onset and complete penetrance

X-linked disorders are dominant or recessive?

recessive

What is the % chance of disease for X-linked disorders for...

male offspring?

female offspring?

male = 50% chance of disease

female = 50% chance of being CARRIER

Which genetic disorder is characterized by a fibrillin protein disorder and irregular connective tissue?

Marfan Syndrome

In Marfan syndrome, abnormal _______ fibers are found where?

elastic fibers

ligaments and aorta

A ruptured aorta and heart valve issues are hallmark signs of what genetic disorder?

Marfan Syndrome

Atlantoaxial instability and basilar invagination couples with ectopia lentils is indicative of what genetic disorder?

Marfan Syndrome

Slender/long limbs, scoliosis, and dural ectasia are indicative of which genetic disorder?

Marfan Syndrome

Which genetic disorder is characterized by defective collagen and decreased tensile strength?

Ehlers-Danlos Syndrome

Vessel fragility and hyperextensibile skin are hallmark signs of what genetic disorder?

Ehlers-Danlos Syndrome

Those with EDS would have a relative contraindication to what?

high velocity adjusting

Which genetic disorder is characterized by impaired LDL transport and breakdown in the liver?

familial hypercholesterolemia

Xanthomas are a hallmark sign of which genetic disorder?

familial hypercholesterolemia

(cholesterol deposits in skin, tendons, eyelids)

Which is the MORE severe form of familial hypercholesterolemia?

Does it have a childhood or adult onset?

homozygous (5x)

childhood

Which is the LESS severe form of familial hypercholesterolemia?

Does it have a childhood or adult onset?

heterozygous (2-3x)

adult

Which genetic disorder is characterized by decreased chloride ion transport and chronic lung infections?

Cystic Fibrosis

Viscous secretions and mucus, specifically in the lungs and pancreas is a hallmark sign of which genetic disorder?

cystic fibrosis

In cystic fibrosis, what the MOST common cause of death?

What does it lead to?

Cor Pulmonale

lung pathology leading to RIGHT sided heart failure

Which genetic disorder is characterized by a decreased breakdown of phenylalanine?

PKU (phenylketonuria)

In PKU, there is too much _______ and too little _______

too much phenylalanine

too little tyrosine

Elevated phenylalanine is associated with what risks?

neurotoxic, intellectual disability, seizures

What is the prognosis/TX for PKU if it is caught during standard newborn screening?

good prognosis, strict dietary restriction of phenylalanine

What is unique about maternal PKU?

phenylalanine crosses placenta barrier

Which genetic disorder is characterized by decreased breakdown of homogentisic oxidase?

Alkaptonuria (AKU)

Black or dark urine is a hallmark characteristic of which genetic disorder?

Alkaptonuria (AKU)

In Alkaptonuria (AKU), homgentisic acid accumulates in what 3 areas primarily?

skin

urine

connective tissues (heart valves and joints)**

Heart valve and joint replacement may be associated with which genetic disorder?

Alkaptonuria (AKU)

Which genetic disorder is characterized by a decreased breakdown of galactose?

galactosemia

In galactosemia, what 3 locations do galactose and galactose-1-phosphate accumulate?

brain, liver, spleen

Which genetic disorder may be associated with "failure to thrive", neurological impairments, and jaundice?

galactosemia

What is the prognosis/TX for galactosemia if it is caught during standard newborn screening?

good prognosis/generally prevented

immediately discontinue lactose exposure

Which genetic disorder is characterized by GM2 gangliosides accumulating in neurons and glial cells?

Tay-Sach's (lysosomal storage disease)

Tay-Sach's can trigger what throughout the nervous system?

What does this lead to?

apoptosis

profound neurological disability

With no treatment, Tay-Sach's is fatal by...

age 3

Which population is at the highest risk for Tay-Sach's disease (1 in 30 carriers)?

Ashkenazi Jews

What is the major defining hallmark for Tay-Sach's disease?

Cherry-red central macula

Which genetic disorder is characterized by an accumulation of glucocerebrosides?

Gaucher (lysosomal storage disease)

99% of Gaucher cases are which type?

Is this the most severe form?

Type 1

less severe (Type II and III are more severe)

Where is the #1 hallmark area that glucocerebrosides accumulate?**

bone marrow

Pancytopenia and Erlenmeyer Flask Deformity are associated with which genetic disorder?

Gaucher

Which genetic disorder is characterized by an accumulation of mucopolysaccharides in CNS and connective tissue?

Mucopolysaccharidosis (lysosomal storage disease)

Which manifestation of MPS is MORE severe and lethal in childhood?

Hurler (Type I)

Which manifestation of MPS is LESS severe associated with a longer life expectancy, but possible valve disease?

Hunter (Type II)

In both manifestations of MPS, ______ sulfate and _______ sulfate accumulate

heparan sulfate and dermatan sulfate

Which glycogen storage disease is HEPATIC and associated with decreased liver glycolysis?

Von Fierkee Disease

Which glycogen storage disease is MYOPATHIC and associated with decreased muscle glycolysis?

McArdle Disease

Which glycogen storage disease is associated with hypoglycemia?

Von Fierkee Disease

Which glycogen storage disease is associated with weakness/cramps, rhabdomyolosis, and ultimately renal failure?

McArdle Disease

Which glycogen storage disease has a GLOBAL effect and is most often associated with cardiomegaly?

Pompe Disease

What is the MOST severe chromosomal disorder?

Is genetic material lost or gained?

monosomy

loss of genetic material

T/F? Trisomy is typically MORE severe than monsomy

False - trisomy genetic material is gained so less severe

Which type of chromosomal disorder is less severe, mostly spontaneous, and can be related to infertility?

Sex chromosome abnormality

What is meiotic nondisjunction?

What is it the MOST common cause of?

faulty anaphase

trisomy 21 (down syndrome)

What is the MOST common chromosomal disorder?

Trisomy

(95% Trisomy 21)

How many chromosomes in Trisomy 21?

47

What is the PRIMARY risk factor associated with Trisomy 21?

advanced maternal age

An increased risk of cardiac malformations, Leukemia, and Alzeheimer's are associated with which chromosomal disorder?

Trisomy 21

What makes up 4% of down syndrome cases and is typically involving chromosomes 14 or 22?

Robertsonian Translocations

What makes up 1% of down syndrome cases?

What is UNIQUE about this?

Mosaics

MITOTIC nondisjunction (not meiotic)

10-30% of patients with what chromosomal disorder present with atlantoaxial instability, abnormal collagen, and joint laxity?

Trisomy 21

Flat facial profile, epicanthic folds, upslanted palpebral fissures and Simian crease are all associated with...

Trisomy 21

What is the name for the deletion syndrome in which a portion of the long arm of chromosome 22 has been deleted?

Di George

Patients with Di George Syndrome present with malformations inn which areas?

chest up!

thymus, parathyroid, brain, face, heart

What does the CATCH pneumonic stand for?

This describes important features of which disease?

cardiac anomalies

abnormal facies

thymic hypoplasia

cleft palate

hypocalcemia

Di George

What is the key difference between Velocardiofacial Syndrome and Di George Syndrome?

Velocardiofacial = NO thymus involvement

Which sex chromosome disorder describes a phenotypically male born with 1 too many X chromosomes?

Klinefelter Syndrome

What is the MOST common combination for Klinefelter Syndrome?

47, XXY

T/F? Klinefelter Syndrome is the result of mitotic nondisjunction

False - MEIOTIC

Which sex chromosome disorder is the MOST common cause of hypogonadism and sterility?

Klinefelter Syndrome

Which sex chromosome disorder describes a phenotypically female born with the absence (or fragmentation) of X chromosome?

Turner Syndrome

T/F? In Turner Syndrome, Absence of X chromosome is LESS severe than fragmentation of X chromosome

False

absence = more severe, monosomy (but still compatible with life)

Amenorrhea, streak ovaries, and infertility are all hallmark signs associated with which sex chromosome disorder?

Turner Syndrome

Aortic coarctation, neck webbing, and a shield like chest are all hallmark signs of which sex chromosome disorder?

Turner Syndrome

Which category of Non-Mendellian single gene disorders worsens each successive generation and is associated with genetic anticipation?**

Triplet-Repeat Mutations

Which category of Non-Mendellian single gene disorders is associated with abnormal oxidative phosphorylation and maternal inheritance ONLY?

Mitochondrial Gene Mutations

Which category of Non-Mendellian single gene disorders is associated with silencing of 1 version of a gene?

genomic imprinting

If a mother has a mitochondrial gene disorder, what are the odds that she passes the gene on?

100%

BUT the gene may not be expressed

Fragile X Syndrome is an example of which category of single gene disorders?

Triplet-Repeat

A moderate expression of Fragile X Syndrome is associated with severe...

cognitive impairment

What is the MOST reliable physical sign of Fragile X Syndrome?

macroorchidism (abnormally large testis)

Leber Hereditary Optic Neuropathy is an example of which category of single gene disorders?

mitochondrial gene disorder