Week 5- Genetic Disorders Flashcards
PART 1
PART 1
All disease s either ________, __________, or a combination of the two. Give examples of each.
Genetic
-cystic fibrosis, sickle cell disease, down syndrome
Environmental
-mercury poisoning
Combination
-DMII, HTN
- National endeavor seeking to identify all human genes and their function.
- Revolution in diagnosis and categorization of genetic disorders, confirmation of new syndromes, reclassification of many congenital malformations.
Human Genome Project (HGP)
Core Competencies for Health Professionals:
- PT practice as ________ and skilled practitioners.
- Need to know when and how to make a _______ (based on S/Sx, taking appropriate family Hx).
- Understand disease etiology and pathogenesis, prognostic indicators, treatment ramifications, neurological outcomes, and lifespan issues.
- independent
- referral
Three Minimum Competencies:
- Appreciate one’s _________ in genetics and expertise.
- Understand the _________ and __________ implications of genetic service.
- Know when and how to make ________.
- limitations
- psychosocial and ethical
- referral
When to Make a Referral:
- History of dysmorphology, brain malformations, epilepsy, abn CT, EEG. abnormal tone, weakness, motor control, dyscoordination, delayed development, sensory disturbances.
- Children with _______ ____, even in absence of __________, should be referred.
-global DD, dysmorphisms
What are the (3) basic types of purely genetic disease?
- ) Monogenic- Mendelian inheritance, a single gene is involved.
- ) Polygenic- Complex inheritance pattern, many genes are involved.
- ) Cytogenetic: Involves large-scale changes in chromosomes.
Molecular Chromosome Studies:
- __________ = Study of chromosomes and their abnormalities.
- __________ = Chromosomes are displayed according to their length. (usually obtained from lymphocytes in blood)
- __________ = Uses chemically tagged chromosome specific DNA probe to label a chromosome sequence and visualize it under a flourescent microscope.
- Cytogenetics
- Karyotype
- FISH
What has revolutionized cytogenetic testing and has high diagnostic yield of genomic abnormalities? This technique is replacing FISH and compares child’s DNA with a control DNA to identify microdeletions/microduplications.
Array Comparative Genomic Hybridization (array CGH)
What are the (4) categories of genetic disorders?
- Chromosomal
- Single gene
- Multifactorial
- Mitochondrial
Chromosomal Disorders:
- Altered structure or number (deletions, inversions, duplications, translocations)
- ___-___% of human conceptions
- 1/160 live births
- Leading cause of _________
- In GENERAL – are not ________
- 10-15%
- miscarriage
- hereditary
Chromosomal Alteration in Number:
- _______ – complete extra set – all are lethal
- __________ – absence (monosomy) or duplication (trisomy) of a chromosome in a cell – usually only one chromosome is affected
- _________ ________– rarely survive
- ________ – most are due to a full trisomy conception followed by loss of extra chromosomes in some cells during mitosis in the embryo – milder clinical manifestation
- Polyploidy
- Aneuploidy
- Autosomal monosomy
- Mosaicism
Chromosomal Alteration in Structure:
- ________- caused by chromosome break.
- ____________ – interchange of genetic material between nonhomologous chromosomes.
- __________ _________– two breaks in different chromosomes with an equal exchange of genetic material, carriers are usually normal but not offspring.
- Deletion
- Translocation
- Reciprocal translocation
General Characteristics of Chromosomal Abnormalities:
- Most are associated with ________ delay and ________ impairment.
- Large number of genes are involved with CNS development.
- Characteristic ________ features.
- Delayed growth, congenital malformations.
- developmental delay and cognitive impairment
- craniofacial
- What are (3) common autosomal trisomies?
- Nearly all associated with advanced _________ _____.
- Down’s Syndrome (trisomy 21), Edwards Syndrome (trisomy 18), Patau Syndrome (trisomy 13)
- advanced maternal age
Name some common genetic disorders. (9)
- Down’s Syndrome
- Turner Syndrome
- Marfan’s Syndrome
- Cri du Chat
- Prader Willi
- Angelman
- Fragile X
- Rett
- Neurofibromatosis
Down Syndrome:
- What is the most common form?
- What are (2) other forms? Describe each.
-Trisomy 21
- Translocation = Extra chromosome 21 is attached to another chromosome, usually 14, 21, or 22.
- Mosaicism = Some cells have 47 and some have 46 (least frequent form)
Down Syndrome:
- What is the most common phenotypic feature of individuals with Down’s?
- Other craniofacial features include Inner epicanthal folds, upward slanting palpebral fissures, flat facial profile, aplasia/hypoplasia of ________ ______, anomalous ears, low nasal bridge, shortened palate, maxillary and ________ hypoplasia, irregular tooth placement.
- Hypoplasia (underdevelopment)
- frontal sinuses, dental
Down Syndrome MSK/CT:
- Most of note is patient joint _______mobility.
- Linear growth deficits, greatest between ___ and ___ months, mostly due to leg length disruption.
- Delayed skeletal maturation rate.
- __/__ overweight by age 3.
- hypermobility
- 6 and 24 months
- 1/3
What are some other systems Down’s affects and which one is the most common health problem?
- Vision/Hearing
- Cardiovascular*** (40%)
- GI
- Neurologic
- Immunologic
With Down Syndrome, how does Neurologic deficits present?
-mild microcephaly, hypotonia, intellectual deficits, DD, EARLY ONSET of Alzheimer’s
Down Syndrome Aging:
- Life expectancy has been _________.
- Changes in body function and structure secondary to aging can lead to ________ restrictions.
- ______ dysfunction (hyper or hypo) a huge problem in adults with DS and can mimic cognitive decline (Alzheimer’s misdiagnosis). What are some symptoms?
- _________ disorders (mitral prolapse in 46-57%) can lead to increased risk of endocarditis, CVA, and HF. Can even occur without prior cardiac findings. What are some symptoms?
- ________
- ________ disorder likely due to premature aging.
- _____/______/_____ and sleep disorders.
- __________ disease affects almost all adults with DS >___yo.
- increasing (9 to 55)
- activity
- Thyroid dysfunction. Symptoms include decreased energy/motivation, weight gain, constipation, bradycardia, and dry skin.
- Cardiac disorders. Symptoms include fatigue, irritability, weight gain, dyspnea, bilateral crackles, 3rd heart sound.
- Obesity
- MSK disorders
- Hearing/vision/skin
- Alzheimer’s Disease, 40yo
Turner Syndrome:
- ____ ________ disorder
- What are the (3) characteristic impairments?
- Other characteristics include dorsal hand/feet edema, hypertelorism, epicanthal folds, ptosis of upper eyelids, elongated ears, shortening of hand bones.
- NUMEROUS ________ anomalies
-sex chromosome disorder
- ) Sexual infantilism
- ) Congenital webbed neck
- ) Cubital valgus
-skeletal
Marfan’s Syndrome:
- Monogenic disorder of _______ ______.
- Is it autosomal dominant or recessive?
- Gene coding for fibrillin protein is FBN1 located on chromosome 15. Mutation of this gene leads to disruption of CT in ________, _____, and ____ system particularly.
- structural proteins
- autosomal dominant
- skeleton, eyes, and CV system
Marfan’s Syndrome:
- Symptoms of skeletal involvement?
- Symptoms of eyes involvement?
- Symptoms of CV system involvement?
Skeletal: long limbs, fingers, toes; hyperextensible joints; deformed chest
Eyes: dislocated lenses due to lax suspensory ligaments in eye
Cardiovascular: aortic dilation with valve regurgitation and aneurysm (dissecting)
What are some common Partial Deletion Disorders?
- Cri-du-Chat
- Prader Willi
- Angelman
- Williams
Cri-du-Chat:
- Partial _______ disorder.
- ___-like cry as infants.
- LBW, hypotonia, feeding difficulties, microcephaly, micrognathia, clumsiness, hyperactivity, mod-sev cognitive impairments.
- partial deletion disorder
- cat-like cry
Prader Willi and Angelman Syndrome:
- PW and AS are examples of differential activation of genes depending on parent from whom they are inherited.
- Both are a deletion of 3-4mb of chromosome ____.
- Inherited from mother = ____________
- Inherited from father = ___________
- chromosome 15
- mother = Angelman Syndrome
- father = Prader Willi
Prader Willi:
- In fetus = ________
- Infancy = Failure to thrive, ________ and _______ difficulties, severe hypotonia
- By 2 = ________ eating may start (_______ becomes a concern), tone usually improves and walking typically achieved by 2
- _______ Issues = temper tantrums, stubbornness, obsessive-compulsiveness
- Wide range of ___________
- decreased activity
- respiratory and feeding
- excessive eating (obesity of concern)
- Behavioral issues
- cognition
Angelman Syndrome:
- ______ ______ Syndrome (no longer used in literature)
- ______ like gait, subtle dysmorphic facial features, frequent and inappropriate laughter
- Ataxia, seizure disorder, sleep disorder
- Happy Puppet Syndrome
- Puppet like gait
What are the (3) types of single gene disorders?
- Autosomal Dominant (Neurofibromatosis)
- Autosomal Recessive
- Sex-linked (Fragile X, Rett)
Fragile X Syndrome:
- Leading hereditary cause of developmental learning disorders.
- More common in ______.
-boys
Rett Syndrome:
- Progressive, almost exclusively in ________. (______ tend to not survive)
- Typical prenatal and perinatal period with normal development up to __-__ months.
- May see mild hypotonia, placid personality and a weak suck and cry.
- Head circumference ______ at birth, decelerates anywhere from __-__ months.
- females (males tend to not survive)
- 6-18 months
- normal, 3-48 months
Rett Syndrome:
- Short period of developmental _________ followed by rapid ________ in motor, language, and psychosocial functions.
- Loss of purposeful _____ motions.
- Gait and truncal ataxia, tremors, apraxia, autistic like behavior, bruxism, breathing irregularities (hyperventilation or episodic apnea), GERD, impaired bowel mobility, LE vasomotor changes.
- stagnation, regression
- hand motions
Rett Syndrome:
- Fits of screaming and crying common by __-__ months.
- Severely impaired _______ skills and cognition, seizures.
- After rapid deterioration, the disease becomes somewhat ______.
- Dystonia results in hand/foot deformities and kyphoscoliosis.
- _______ occurs early.
- 18-24 months
- language skills
- stable
- osteoporosis
Metabolic disorders include those involving what? (4)
- amino acid metabolism
- carbohydrate metabolism
- lysosomal storage
- urea cycle disorders
Phenylketonuria (PKU):
- ______ _______ of the monogenic amino acid disorders.
- Autosomal ________ disease.
- Caused by a deficiency of phenylalanine hydroxylase.
- Phenylalanine and phenylpyruvate accumulate in blood and appear in urine.
- Symptoms include severe ________ _________.
- most common
- autosomal recessive disorder
- severe mental retardation
___________ is the most common monogenic disorder of carbohydrate metabolism.
-Galactosemia
Neurofibromatosis:
-Point mutation in _____ gene leads to loss of cell differentiation and uncontrolled cell growth. Therefore, the NF1 gene is considered a tumor suppressor gene.
-NF1 gene
