Genetic Syndromes Flashcards
all disease is either _____ or _______ or _______
genetic or environmental or a combo of the two
give an example of a purely genetic, environmental and combination disease
- purely genetic → cystic fibrosis, sickle cell disease
- environmental → mercury poisoning
- combination → DM type II, HTN
List the 3 Minimum PT Competencies pertaining to genetics
- appreciate one’s limitations in genetics and expertise – ID need for continuing edu
- understand the psychosocial and ethical implications of genetic service
- know when and how to make a referral
when to make a referral
- History of:
- dysmorphology
- brain malformations
- epilepsy
- abd CT
- EEG
- abnormal tone
- weakness
- motor control, discoordination
- delayed development
- sensory disturbances
- children with global DD (even in absence of dysmorphisms)
What are the 3 types of purely genetic disease
- Monogenic
- Mendelian inheritance, a single gene is involved
- Polygenic
- complex inheritance pattern, many genes are involved
- Cytogenic
- involves large-scale changes in chromosomes
list relevant terms pertaining to genetics
- Gene
- Locus
- Alleles
- Homozygous
- Heterozygous
- Genotype
- Phenotype
define cytogentics
study of chromosomes and their abnormalities
define Karyotype
chromosomes are displayed according to their length
what is FISH?
a technique in which chemically tagged chromosomes specific DNA probes to label a chromosome sequence and visualize it under flourescent microscope
what is an array CGH?
Array Comparative Genomic Hybridization
- compares child’s DNA with a control DNA to ID microdeletions or microduplications
- revoluntionized cytogenic testing
- high diagnostic yield of genomic abnormalities
- this technique is replacing FISH for subtelomere imbalances
List the 4 categories for genetic disorders
- chromosomals
- single gene
- multifactorial
- mitochondrial
briefly describe the category of “chromosomal disorders”
- two subtypes:
- altered in structure or number
- includes:
- deletions, inversions, duplications, translocatoins
- 10-15% of human conceptions
- 1/160 live births
- leading cause of miscarriage
- in general → not hereditary
chromosomal disorders can be due to an alteration in number of chromosomes. List terms assocaited with this
- Polyploidy
- Aneuploidy
- Autosomal monosomy
- Mosaicism
define polyploidy
complete extra set of chromosomes → all of these diseases are lethal
define aneuploidy
absence (monosomy) or duplication (trisomy) of a chromosome in a cell → usually only one chromosme is affected
how often do children with an autosomal monosomy survive?
rarely
define mosaicism
most of these are due to a full trisomy conception followed by loss of extra chromosomes in some cells during mitosis in the embryo
milder clinical manifestation
List general characteristics assocaited with chromosomal abnormalities
- most are assocaited with developmental delay and cognitive impairment
- large number of genes are involved with CNS development
- characteristic craniofacial features
- delayed growth
- congenital malformations
List common autosomal trisomies
- Down syndrome
- Edwards syndrome
- Patau syndrome
nearly all autosomal trisomies are associated with what?
advanced maternal age
Describe Down Syndrome
- Trisomy 21 → most common form
- phenotypic feature → hypoplasia is the most common element of the many phenotypic features
List craniofacial features in Down Syndrome
- inner epicanthal folds
- upward slanting palpebral fissures
- flat facial profile
- aplasia/hypoplasia of frontal sinuses
- anomalous ears
- low nasal bridge
- shortened palate
- maxillary and dental hypoplasia
- irregular tooth placement
List MSK/CT features in Down Syndrome
- Diastasis recti
- joint hypermobility
- atlantoaxial instability w/risk of spinal cord compression
- simian creases
- wide gap between toes 1 and 2
- hypoplasia of the middle phalanx of 5th clinodactyly
- hypoplastic pelvis w/shallow acetabular angle
- linear growth deficits
- greatest between 6-24 months
- mostly due to leg length reduction
- delayed skeletal maturation rate
- 1/3 overweight by age 3
Eyes/Vision and Ears/Hearing features in Down Syndrome
- Eyes
- iris speckling (brushfield’s spots)
- myopia
- nystagmus
- strabismus
- tear duct blockage
- Ears
- conductive hearing loss
- sensorineural hearing loss
- mixed hearing loss (as many as 78%)
Cardiovascular features in Down Syndrome
- CHD is most common health problem with 40% having malformations
- ventricular septal defects
- patent ductus arteriosus
- tetralogy of Fallot
GI features in Down Syndrome
- duodenal stenosis/atresia
- imperforate anus
- Hirschprung’s disease → paralysis in some of the intestines
Neurologic features in Down Syndrome
- mild microcephaly
- hypotonia
- intellectual deficits
- developmental delay
- early onset of AD
- small cerebellum and brainstem
- reduction in number of neurons and dendritic spines
- increased latency of response
- delayed dissoluation of primitive reflexes
- delayed emergence of RR
Immunologic features in Down Syndrome
- leukemia
- chronic rhinitis and conjunctivitis
- fluid in middle ear
Aging in Down Syndrome and implications for PT
- life expectancy has been increasing
- currently → 55 yrs or older
- changes in body function and structure secondary to aging have potential to lead to activity restrictions
Thyroid dysfunciton and Down Syndrome
adults with DS at high risk for Thyroid Dysfunction
Hypothyroidism → mimics cog decline (can be misdx as AD)
Cardiovascular disorders in Down Syndrome
at higher risk for developing:
- mitral prolapse
- endocarditis
- CVA
- HF
- reduced cardiovascular function
- reduced capacity
- lower mean O2
- lower min vent
- lower HR during exercise
MSK conditions in Down Syndrome associated with aging
- premature aging may lead to early experience of MSK disorders generally associated with elderly populations
- mild cervical arthritis
- hip dysplasia w/dislocation
- foot pronation
- osteoporosis
T/F: almost all adults with DS over the age of 40 demonstrate some form of AD
TRUE
demonstrate neuropathy consistent with AD
List 2 sex chromosome disorders
- Turner
- Klinefelter
what are the classic impairments with Turner syndrome?
- sexual infantilism
- congenital webbed neck
- cubitus valgus
what are other impairments associated with Turner’s syndrome?
- dorsal edema of hands and feet
- hypertolerorism
- epicanthal folds
- ptosis of upper eyelids
- elongated ears
- shortening of hand bones
- numermous skeletal anomalies
what is Marfan Syndrome?
monogenic disorder of structural protein (fibrillin)
mutation of gene leads to disruption of CT in skeleton, eyes and cardiovascular system
Symptoms of Marfan syndrome
- Skeletal
- long limbs, fingers, toes
- hyperextensible joints
- deformed chest
- Eyes
- dislocated lenses due to lax suspensory ligaments in eye
- Cardiovascular
- aortic dilation w/valve regurgitation
- aortic aneursym (dissecting)
List several Partial Deletion Disorders
- Cri-du-chat
- Prader Willi
- Angelman
- Williams
briefly describe Cri-du-Chat
- cat cry as infants
- low birth weight
- hypotonia
- feeding difficulties with failure to thrive
- microcephaly
- micrognathia
- clumsiness
- hyperactivity
- moderate to severe cognitive impairments
how are Prader Willi (PW) and Angelman Syndrome (AS) the same/different?
- Same
- both are examples of differential activation of genes depending on parent whom they are inherited
- same section of chromosome is deleted
- Differnet
- if on chromosome from mother → AS
- if on chromosome from father → PW
by 2 years of age what is a major concern for PW?
obesity due to excessive eating
behavioral issues like temper tantums, stubbornbess, and OCD
describe AS
- used to be called Happy Puppet Syndrome
- puppet like gait
- subtle dysmorphic face
- frequent and inappropriate laughter
- ataxia
- seizure disorder
- sleep disorder
describe Williams Syndrome
- elfin like face
- wide mouth with full lips
- ADHD
- LD
- mild cog impairments
- decreased visuospatial skills
- early joint laxity with later compensations
- sensory defensiveness
what is the cause of Williams Syndrome
partial deletion disorder
results in a disturbance in elastin gene
williams syndrome individuals are usually very talented in what way?
muscially
what are the 3 types of single gene disorders?
- Autosomal Dominant
- Autosomal Recessive
- Sex-linked
list several autosomal dominant gene disorders
- osteogenesis imperfecta
- tuberous scleoris
- neurofibromatosis
list several autosomal recessive gene disorders
- cystic fibrosis
- hurler syndrome
- PKU
- SMA
list several sex-linked gene disorders
- hemophilia A
- Fragile X
- Lesch-Nyhan
- Rett
what is Fragile X Syndrome?
- leading hereditary cause of developmental learning disorders
- more common in boys than girls
what is Muscular Dystrophy?
- Group of hereditary myopathies
- characterized by:
- progressive muscle weakness
- deterioration, destruction, regeneration of muscle fibers
- muscle fibers gradually replaced by fibrous and fatty tissue
List several different types of Muscular Dystrophy
- Becker
- Congenital
- Congenital/myotonic
- Child onset facioscaphum
- Emery-Dreifus
what is Rett Syndrome?
- Progressive sex-linked disorder almost exclusive in females
- males tend to not survive
- characterized by:
- short period in which development stagnates followed by rapid degeneration in motor, language, and psychosocial functions. the disease then becomes somewhat stable
- dystonia results in hand and foot deformities
- osteoporosis can occur early
Characteristic of Rett Syndrome impacting the hands
loss of purposeful hand motions → replaced with characteristic hand wringing
what is the culprit behind enzyme deficiencies?
genetic mutations in the genes that code for that enzyme
this deficiency leads to accumulation of precurors and likely disease → called metabolic disorders
metabolic disorders include:
- amino acid metabolism
- carbohydrate metabolism
- lysosomal storage
- urea cycle disorders
what is the most common monogenic amino acid disorder?
Phenylketonuria
- autosomal recessive disease
- phenylananine and phenylpyruvate accumualte in blood and urine
- symptoms include severe mental retardation
what is the most common monogenic disorder of carbohydrate metabolism?
Galactosemia
- individuals cannot effectively convert galactose to glucose so it accumulates in tissues
- clinical signs:
- failure to thrive
- hepatic trouble
- cataracts
- developmental delay
list 2 lysosomal storage diseases
- Sphingolipidoses
- results in multiorgan dysfunction
- Tay-Sachs disease
- a disorder common among Ashenazi Jews
- mental retardation, hearing and vision loss are hallmarks
List a disorder that is a monogenic disease of regulatory proteins
Neurofibromatosis type I
- a point mutation in this gene leads to loss of:
- cell differentiation
- uncontrolled cell growth
- thus considered a tumor suppressor gene
- characterized by:
- disfiguring with cafe-au-lait spots
- fibromas
- lisch nodules in eyes
