Genetic Disorders Flashcards
Autosomal Dominance
75% familial
refers to a single mutant allele from an affected parent that is transmitted to an offspring regardless of sex
affected parent has 50% chance of transmitting disorder to each offspring
systems often involved are the skeletal, ocular and cardiovascular
Autosomal Recessive
manifested only when both members of the gene pair are affected
both parents may be unaffected but are carriers of the defective gene
affect both sexes
occurrence risks in each pregnancy are 1:4 for an affected child, 2:4 for a carrier child and 1:4 for a normal (non-carrier, unaffected) homozygous child
Marfan Syndrome
Pathogenesis: mutations in a gene on chromosome 15 that codes for fibrillar (component of microfibrils)
Microfibrils serve as scaffolding for elastin and are integral for elastin fibers
affects ocular, CV and skeletal
Skeletal: long, thin body with exceptionally long extremeities and long tapering fingers (arachmodactyly), hyperextensible joints and spinal deformities (kyphosis and scoliosis)
Chest: pectus excavatum and pectus carinatum
Mitral valve prolapse, progressive dilation of the aortic valve ring and weakness of aorta and other arteries
Ocular: bilateral dislocation of the lens due to weakness of the suspensory ligaments, myopia and predisposition to retinal detachment
Klinefelter’s Syndrome (XXY)
testicular dysgenesis accompanied by the presence of one or more extra X chromosome in excess of the normal male XY complement
results from non-disjuction during meiotic division in one of the parents
male phenotype retained
low testosterone levels, tall stature, abnormal body proportions, lower part of body is larger than the upper part
female distribution of subcutaneous fat and variable degrees of breast enlargement
management requires a comprehensive neurodevelopment evaluation
men will have congenital hypogonadism, inability to produce testosterone at normal levels
large breasts, sparse facial and body hair, small testes and inability to produce sperm
Turner’s Syndrome (X/0)
absence of all or part of one of a female’s two X chromosomes
girls are short in stature, but body proportions are normal
Absence of the ovaries, no menstruation, and shows no signs of secondary sex characteristics
variations in abnormalities range from none to webbing of the neck with redundant skin folds, non pitting lymphedema of the hands and feet and congenital heart defects, particularly coarctation of the aorta and bicuspid aortic valve.
Abnormalities in kidney development.
changes in nail growth, high arched palate, short fourth metacarpal and strabismus
Health concerns for adult women are increased morbidity due to cardiovascular disease, and gastrointestinal, renal and endocrine disorders.
Adults with Turner syndrome continue to have reduced bone mass, and has been associated with increased risk of fractures
Down Syndrome
Trisomy 21 causes a combination of birth defects including some degree of intellectual disability, characteristic facial features and other probelms
it is the most common chromosomal disorder
Approx 95% of cases are caused by an error in cell division during meiosis, resulting in a trisomy of chromosome 21.
risk fo having a child with down syndrome increases with maternal age.
Physical Features with Down Syndrome (facial features most important)
Physical features of a child with down syndrome are distinctive, and usually known at birth
growth delay
a small and rather square head
flatter facial profile
small nose
somewhat depressed nasal bridge
small folds on the inner corners
of the eyes
upward slanting of the eyes
small, low set and malformed ears
fat pad on the back of the neck
an open mouth, larger, protruding tongue
childs hands are usually short and stubby, with fingers that curl inward, and there usually is only a single palmar crease
excessive space between the large and second toe
hypotonia and joint laxity are present in infants and young children
congenital heart defects and increased risk of gastrointestinal malformations
much greater risk of development of acute leukemia among children with down syndrome
increased risk of Alzheimers disease
Neurofibromatosis
condition involving neurogenic tumors that arise from Schwann cells an other elements of the peripheral nervous system
two genetically and clinically distinct forms of the disorder:
type 1 NF (von Recklinghausen disease)
type 2 bilateral acoustic NF
both of the disorders result from a genetic defect in a tumor-suppressor gene that regulates cell differentiation and growth
Type 1 NF (von Reclinghausen Disease) (Chromosome 17)
Type 1NF is relatively common and approx 50% of cases have a family history of autosomal domination transmission and the remaining 50% appear to represent a new mutation.
Characterized by multiple neural tumors (neurofibromas) dispersed anywhere on the body, numerous pigmented skin lesions, some of which are café au lait spots; and pigmented nodules (Lisch nodules) of the iris
cutaneous neurofibromas (vary in number from a few to hundreds) manifest as soft, pedunculate lesions that project from the skin, apparent at puberty, most dense over trunk
Plexiform neurofibromas involves the larger peripheral nerves and tend to form large tumors that cause severe disfigurement of the face, overgrowth of an extremity, or skeletal deformities (scoliosis)
Children with NF-1 are susceptible to neurologic complications
increased incidence of learning disabilities, ADD and abnormalities of speech
Complex partial and generalized tonic-clonic seizures
NF-1 is also associated with increased incidence of other neurogenic tumors (meningiomas, optic gliomas, pheochromocytomas)
Type 2 NF (chromosome 22)
tumors of the acoustic nerve and multiple meningiomas
Often asymptomatic through first 15 years of life.
Most frequent symptoms are headaches, hearing loss, and tinnitus
May be associated intracranial and spinal meningiomas
Often made worse by pregnancy and oral contraceptives may increase the growth and symptoms of tumors
severe disorientation may occur during diving or swimming underwater, and drowning may result.
Surgery may be indicated for debunking or removal of the tumors
Tay Sachs
a lysosomal storage disease
gangliosides (failure of lysosomes to breakdown the GM2 ganglioside of cell membranes
inherited as an autosomal recessive trait
lipid accumulation in all organ lysosomes, failure for breakdown of GM2
destroys the brain and retina neurons
infants normal at birth, but manifest with progressive weakness, muscle flaccidity and decreased attentiveness at 6-10 months.
followed by rapid deterioration of motor and mental function
fatal, death occurs before 4-5 years of age
Multifactoral Genetic Disorder
caused by multiple genes and in many cases environmental factors
threshold phenomena, factors contributing to the trait can be compared to water filling a glass
e.g. the expression of the disorder occurs when the glass overflows
can be expressed during fetal life and be present at birth or may be expressed later in life
congenital disorders that are thought to arise through multifactorial inheritance includes
* cleft lip or palate * clubfoot * congenital dislocation of the hip * congenital heart disease * urinary tract malformation
environmental factors can play a greater role in disorders of multifactorial inheritance that develop in adult life such as
* coronary artery disease * diabetes mellitus * hypertension * cancer * common psychiatric disorders (bipolar disorder and schizophrenia)
Characteristic Patterns of Multifactorial Genetic Disorders
1st: multifactorial congenital malformation involve a single organ or tissue derived from the same embryonic developmental field
2nd: the risk of recurrence in future pregnancies is for the same or similar defect (parents of a child with a cleft palate defect have an increased risk of having another child with a cleft palate, but not with spina bifida)
3rd: the increased risk (compared to the general pop.) among first-degree relatives of the affected person is 2-7% and among second-degree relatives it is approx one-half that amount
the risk increases with increasing incidence and severity of the defect among relatives
Cleft Palate/Lip
fetus is most susceptible at day 35 when the frontal prominences of the craniofacial structures fuse with the maxillary processes to form the upper lip
caused by:
disturbances in gene expression (hereditary or environmental)
teratogens (rubella, anticonvulsant drugs)
chromosomal abnormalities
TORCH Syndrome
infectious organisms that cross the placenta
Toxoplasmosis (undercooked meats, cat litter)
Other (EBV, herpes zoster, syphilis, HIV)
Rubella (hearing impairment, blindness, neurological issues in developing countries
Cytomegalovirus (brain damage in fetus)
Herpes Simplex 2 (septic, because newborn was exposed when they came out of the birth canal)
Common Manifestations: Microcephaly, hydrocephalus (fluid in brain), eye defects, blindness, hearing deficits, deafness
