Genetic Disorder Pathology Flashcards
What are common clinical presentations for down syndrome?
- Hypotonia (“floppy babies”; poor muscle tone)
- Excess nuchal skin
- Epicanthic Folds
- Protruding tongue
- Small ears
- Upward sloping palpebral fissures
- Single palmar crease
- Atrial and Ventricular Septal Defects
- Anal or Duodenal Atresia
- Short stature
- Strabismus (eyes do not line up)
What are some common health problems that develop from Down Syndrome?
- Congenital Heart Disease (40%)
- Intellectual Disability
- Alzheimer Disease (APP gene on C21)
- Decreased life expectancy
What are comon clinical presentations for Trisomy 13 (Patau Syndrome)?
- Severe cleft lip/palate
- Polydactyly
- Mean survival of 7 days
- Microcephaly (small than average head)
What are common clinical presentations for Trisomy 18 (Edward’s Syndrome)?
- Microcephaly
- CNS & CVS Malformations
- Prominent Occiput (Back of Head)
- Micrognathia (lower jaw smaller than normal)
- Overlapping fingers
- Rocker-bottom feet (sole flexes convexly)
- Mean survival of 14.5 days
What are common clinical presentations for Turner Syndrome?
- Short stature
- Delayed pubertal development
- Amenorrhea
- Gonadal dysgenesis ~ streak ovaries
- Webbing of neck
- Broad chest and widely spaced nipples
Turner Syndrome mechanism?
45X or 45 XO
What percentage of Turner Syndrome birth cases are mosaics?
75%
What are common clinical presentations for Klinefelter syndrome?
- Feminization of secondary sex characteristics (hair and breasts)
- Hypogonadism (sex glands produce little, if any hormones)
- Disproportionate long limbs
- Tall and thin stature
Klinefelter Syndrome mechanism?
47 XXY
What do other trisomies of sex chromosomes have in common?
Tall statures and mental deficits
What happens to individuals when they have high numbers of X chromosomes?
As the X chromosomes increase, the mental impairment does as well.
How are extra X chromosomes inactivated?
Barr bodies
Although individuals may not be affected by balanced rearrangements of chromosomes, what might happen later?
Their children might be at risk of developing an unbalanced abnormality.
What do multiple congenital anomalies in the absence of an obvious diagnosis suggest?
A chromosomal aberration or abnormality.
What are the five acrocentric chromosomes in humans?
13, 14, 15, 21, and 22
What is the name of a balanced recombination of the p-arms of two acrocentric chromosomes?
Robertsonian Translocation
What is the most common down syndrome translocation and how is this inherited?
14q21q
- 2/3 are de novo
- 1/3 inherited from a balanced carrier
What type of translocation carrier has children that are at risk for BOTH down syndrome and patau syndrome?
13q21q
100% of live-born offspring of this type of balanced carrier will have down syndrome?
21q21q
What are the two possible gametes for 21q21q?
- Nullisomic C21 (no copies - lethal)
2. Disomic C21 (2 copies - Down Syndrome)
What are some common clinical presentations for Wolf-Hirschhorn Syndrome?
- Characteristic facies ~ broad, flat nasal bridge, high forehead (“Greek Warrior Forehead”)
- Severe mental deficiency
- Hypotonia
- Microcephaly
What is the mechanism for Wolf-Hirschhorn Syndrome?
It is an autosomal deletion disorder (4p-) of the 4p16 critical region.
What are some common clinical presentations for Cri du Chat Syndrome?
- Cat-like cry (high pitched cry)
- Microcephaly
- Downward sloping palpebral fissures (down syndrome has upward sloping)
- Hypertelorism (increased distance between two body parts)
What is the mechanism for Cri du Chat syndrome?
It is an autosomal deletion disorder (5p-). Usually ends in a loss of 10-20% of distal p arm in most cases.
What are some common clinical presentations for cystic fibrosis?
- Obstructive lung disease
- Lung infections
- Malabsorption (pancreatic insufficiency)
- Salty sweat
- Male infertility
- Meconium ileus (obstruction of SI)
Explain the Sickle Cell Anemia mechanism.
Sickle Cell is an Autosomal Recessive Disease that is caused by an A to T transversion in the HBB coding ß-globin (missense mutation). Due to this, the amino acid glutamic acid (E) is changed to valine (V).
What are some common clinical presentations for sickle cell anemia?
- high recticulocytes
- splenomegaly
- painful swelling of hands and feet
- repeated infections
A single gene affects multiple, seemingly unrelated, phenotypic traits.
Pleiotropy
Sickle Cell Mutations alter a recognition sequence meant for restriction endonuclease. What is this sequence name?
MST II
Hemophilia A and B have mutations in what blood clotting factors?
A - Factor VIII (F8 gene)
B - Factor IX (F9 gene)
40% of severe Hemophilia A cases are caused by what mechanism?
A chromosomal inversion that developed from unequal crossing over between repeats. The inversion changes the distances between restriction sites and changes the sizes of fragments.
What autosomal dominant disorder is considered the most common microdeletion syndrome?
DiGeorge Syndrome or Deletion Syndrome or Velocardiofacial Syndrome
What is the mechanism for Deletion Syndrome?
22q11 Microdeletion
What are some common clinical presentations for 22q11 Deletion Syndrome?.
CATCH-22:
C - Cardiac Defects A - Abnormal facies T - Thymic Hypoplasia C - Cleft palate H - Hypocalcemia from parathyroid aplasia 22: Chromosome 22
