Genetics

consultand

person seeking genetic counseling, usually a relative of affected person

proband

affected individual who 1st brings genetic condition to medical attention

cascade testing

process of informing family members of a genetic condition that was discovered within the family, leading to other family members getting tested for the same condition

genetic counselors

Who can best determine which family members should be tested first?

genetic information non-discrimination act (GINA)

genetic test results are protected under what act?

discrimination

GINA does not protect individuals from…

autosomal dominant

autosomal recessive

x-linked

What are the inheritance patterns for single-gene disorders?

extra/missing chromosomes

large-scale deletions or duplications

translocations

inheritance patterns for chromosomal disroders

maternal transmission

neurological or neuromuscular sx

inheritance patterns for mitochondrial disorders

multiple genetic and environmental factors

inheritance patterns multifactorial disorders

autosomal dominant

single gene disorder

Huntington’s, Marfan

What are two examples of autosomal dominant dx?

marfan’s syndrome

connective tissue disorder w/ autosomal dominant inheritance

tall, thin, gangly

arachnodactyly

joint hypermobility

aortic and cardiac dx, aneurysm

ectopia lentis

crowded teeth

scoliosis

pectus deformity

Marfan syndrome characteristics?

MVP

aortic aneurysm

retinal detachement

fibrillin defect

arachnodactyly

negative nitroprusside test

subluxated lense

What does MARFANS stand for?

FBN1 gene, chromosome 15

Marfan is usually inherited via genetic mutation in what gene?

fibrillin-1 protein

FBN1 gene is responsible for production of what protein?

physical exam, sx, genetic testing

Diagnosis for marfan?

prevent complications (BB, avoid contact sports, strenuous activity, FBN1 gene, avoid pregnancy)

How to prevent complications of marfan?

aortic root surgery & valve replacement, correct dislocated lens, scoliosis, pectum issues

Preventative sx for marfan?

cystic fibrosis, tay-sachs, sickle cell disease

Examples of autosomal recessive?

genetic mutation in beta globin chain of hgb

What is the mutation for sickle cell disease?

malaria

Sickle cell disease carriers a resistant to what?

sickle/crescent moon shape, and become rigid & sticky, lose flexibility & sickle cell lodges in the capillaries

How do the RBC change in sickle cell?

blocks blood flow, ischemia occurs downstream

Eventually what happens in sickle cell disease due to the abnormally shaped RBCs?

eventually RBC cannot revert to normal shape

Snowball effect for sickle cell dx

painful crises

extreme fatigue

visual problems

delayed growth/puberty

jaundice

hand foot syndrome

splenomegaly & hepatomegaly

lung & kidney damage

stroke

priapism

risk of sickled cells rupturing causing hemolytic anemia

Sickle cell symptoms?

amniotic fluid sampling pre-birth

sickledex (sickle cell screen or sickle cell solubility)

hgb electrophoresis is definitive

CBC w/ peripheral blood smear

Sickle cell dx?

analgesia, hydration/IVFs, oxygen, transfusion

How to treat painful crises of sickle cell dx?

antibiotics

How to prevent infections for sickle cell?

slows sickle formation

How does hydroxyurea work for sickle cell?

bone marrow

What transplant can treat sickle cell?

folic aid

What supplement should someone take daily with sickle cell?

autosomal dominant, autosomal recessive

What kind of genetic pattern does ehlers danlos syndrome have?

hyperelasticity of skin, hypermobility of joints, multiple vascular effects

Ehlers-danlos syndrome classic sx?

no affected sons, all daughters are affected

A male with an x-linked dominant disease will affect their offspring how?

50% chance of passing condition to each son or daughter

A female with an x-linked dominant disease will affect their offspring how?

rett syndrome

rare genetic neurological disorder, primarily affects females, as males rarely survive infancy

MECP2 gene

Rett syndrome has a mutation in what gene?

loss of speech and purposeful hand use

Sx of Rett syndrome?

developmental regression between 6-18 months of age

When does developmental regression occur in Rett Syndrome?

clinical dx

Diagnosis dx?

no cure, symptom management, improve QOL, multidisciplinary tea, medications (anti-seizure)

Tx of Rett Syndrome?

2

For an x-linked recessive dx how many bad alleles does a female need to be affected?

duchenne muscular dystrophy, red-green colodblindness, hemophilia A

Examples of x-linked recessive dx?

elevated CK levels at birth, genetic test, muscle biopsy

How is the diagnosis of duchenne muscular dystrophy made?

defective gene, responsible for production of dystrophin, DMD gene mutation

Duchenne muscular dystrophy is caused by what mutation?

dystrophin

this links thin filaments to integral proteins on sarcolemma and provides mechanical reinforcement to sarcolemma keeping it intact

muscle fibers degenerate and muscle weakness occurs

When dystrophin is defective what happens?

damage to contractile fibers, muscle does not regenerate then the cells undergo apoptosis & muscle mass drops

What happens when excessive calcium enters after the sarcolemma tears during contraction?

weakness, growth delay, cardiomyopathy, orthopedic complications, cognitive and behavioral disorders, frequent falls, not rise from lying/sitting, waddling gait, walk on toes, respiratory insufficiency

DMD sx are characterized by?

gower’s sign (+ calf pseudohypertrophy)

What sign do we see in DMD that is secondary to proximal hip muscle weakness?

sustain mobility and respiratory function, slow disease progression, improve QOL

What are the goals of DMD treatment?

spinal braces, wheelchair, PT, OT, steroids to preserve muscle function, gene therapy

What supportive care can be given for DMD ?

sex chromosome aneuploidy

atypical number of X and/or Y-chromosomes beyond the typical XX or XY complement

developmental difficulties, impacting cognition and behavior (turner syndrome, klinefelter, 47 XYY)

Sex chromosome aneuploid is associated with increased risk for what?

absence of 2nd sex chromosome, 45 XO, phenotypically female

What is the chromosome abnormality in turner syndrome?

webbed neck

short stature

wide spaced nipples

bicuspid aortic valve

bilateral streak gonads

underdeveloped mullerian tract

Signs of turner syndrome?

bilateral streak gonads

ovaries are mainly made of fibrous tissue, functionless tissue — sign of turner syndrome

fallopian tubes, uterus, vagina

The mullerian tract eventually becomes what?

prenatal usually amniotic fluid testing, physical examination & karyotype analysis

Diagnosis of turner syndrome?

no cure

daily GH therapy in childhood

estrogen replacement therapy to induce puberty

multidisciplinary routine echo & BP checks

check thyroid disorders

check hearing often

DEXA scan for osteoporosis

learning support

IVF for pregnancy

Tx of turner syndrome?

XXY genotype causing low androgen production, phenotypically male

What is the gene mutation in kleinfelter’s syndrome?

tall stature

small penis and rudimentary testes

breast development

weak libido

possible infertility

high incidence of cognitive deficiency

Signs of kleinfelter’s syndrome?

superman syndrome or jacobs

extra y-chromosome causing increased height, speech delay, taller stature

autosomal dominant, deletion of submicroscopic deletion of chromosome 22q

Genetic mutation for DiGeorge Syndrome

congenital heart defects

immune deficiency

cleft lip and palate

hypocalcemia

learning difficulties

characteristic facies

Primary features of DiGeorge Sydrome?