All CTMD Diseases Flashcards
Defects in cilia
primary ciliary dyskinesia
Defects in primary cilia
ciliopathies
Three inherited collagen disorders
Ehlers-Danlos, OI, osteoarthritis
Acquired collagen disorder and what step
Scurvy. Can’t hydroxylate proline, PROLYL HYDROXYLASE –> requires vit C as cofactor
Marfan’s Syndrome
defect in elastic tissue, fibrillin gene
Sacrococcygeal Teratoma
occurs when remnants of primitive streak persist as pluripotent cells proliferating in buttocks region
Hirschsprung Disease
failure of neural crest cells to migrate into wall of developing large intestine, reduced diameter of distal colon caused by tonic contraction of non-innvervated muscles “backs up” system and causes dilation of more proximal segments
polyhydramnios and oligohydramnios
excess and decreased amounts of amniotic fluid, respectively
Both conditions may indicate presence of birth defects such as esophageal atresia, or defective kidneys
achondroplasia (what and cause)
most common form of dwarfism, affects long bones
Cause: mutation in FGF receptors
craniosynostosis (what and cause)
premature closure of one or more cranial sutures, malformed cranium
Cause: mutation in FGF receptors
polysyndactyly (what and cause)
extra fused digits
Cause: Mutations in HOXD13 gene
holoprosencephaly
broad spectrum of defects based upon defective formation of forebrain
Cause: mutations in SHH gene (SHH is secreted by prechordal plate and induces forebrain formation)
hypotelorism
underexpression of SHH, eyes close together, proboscis
hypertelorism
overexpression of SHH, eyes far apart
Renal-Coloboma Syndrome
mutation in PAX2 gene
clefting defect of eye, underdevelopment of kidney
brachycephaly
flat head syndrome
palpebral fissure
line from inner to outer corners of eyes
philtrum
groove in area between upper lip and nose
micrognathia
undersized jaw
frontal bossing
development of unusually pronounced forehead as result of enlarged frontal bone
omphalocoele
abdominal wall defect in which liver and intestines remain outside in a sac because of a defect in development of muscles of abdominal wall, oftentimes correlated with genetic defects (60% of time)
gastroschisis
defect in anterior abdominal wall through which abdominal contents freely protrude, not usually correlated with genetic anomaly
Robin malformation sequence
micrognathia –> displacement of tongue (glossoptosis) –> cleft soft palate
VACTERL association
VACTERL association: vertebral defects, anal atresia, cardiac defects, tracheo-esophageal fistula, renal anomalies, and limb abnormalities
Not related in any obvious way
Common findings in triploidy
- microsomia
- fused 3rd and 4th fingers
Down Syndrome chromosomal abnormalities
94% trisomy 21 (usually originate from mother, risk of non-disjunction with increasing maternal age)
3% mosaic
3% trisomy 21 due to unbalanced translocation
Down Syndrome Clinical Findings
- short stature
- developmental delay/mental retardation
- upslanting palpebral fissures
- increased skin on back of neck
- hearing loss
Causes of death in Down Syndrome
Infancy: heart disease (do EKGs early to identify any heart defects), leukemia, respiratory issues
Late adult: worsening immune system, premature aging, early-onset dementia
Trisomy 18/Edward’s Syndrome
Common with 13: heart disease, rocker bottom feet, poor survival, mental retardation
DISTINCT: omphalocoele, micrognathia, 5 over 4 and 2 over 3
Survives longer than 13 usually (~1 year)
Trisomy 13
Common with 18: heart disease, rocker bottom feet, poor survival, mental retardation
DISTINCT: polydactyly, cleft lip/palate, holoprosencephaly
Lives only for about a month
Turner Syndrome
45, X
- short stature, streak gonads, amenorrhea, webbed neck, prominent ears, shield chest, renal malformations common, 20% have congenital heart disease (coarction of aorta)
Klinefelter
47 XXY
- appear normal until puberty, hypogonadism, infertility, tall, male breast enlargement, behavioral problems
XYY
- pretty normal, sometimes taller
XXX
- no obvious increase in malformations
- sometimes tall, some fertility problems
- sometimes learning disabilities
Cri du Chat
- 5p-
- shrill cry
- microcephaly, round face, ocular hypertelorism, epicanthal folds, downslanting palpebral fissures, single transverse palmar crease, hyptotonia
- Later: mental retardation, good survival
- Do parental studies! –> determine carrier status to see if there was unfavorable segregation from parent with unbalanced reciprocal translocation
Wolf-Hirshhorn
- 4p-
- microcephaly, frontal bossing, cleft palate/lip, micrognathia, seizures
- survival is poor
- Parental studies
Prader-Willi
- 60-70% with deletion on 15q paternal
- In non-deletion cases, maternal UPD
hypotonia, mental deficiency, progressive obesity with compulsive eating, hypopigmentation
Angelman
- deletion on maternal 15 or paternal UPD
- severe mental retardation, microcephaly, unprovoked laughther, hypopigmentation
- With age: wide mouth, thin upper lip, widely spaced teeth
Williams Syndrome
- 7q- (includes gene for elastin)
- elfin face, aortic stenosis, wide mouth, loquacious personality, music ability, stellate pattern of iris, developmental delay
- Can only use FISH (parent chroms normal)
Deletions 22q11.2 Syndromes
- DiGeorge: anormalities of thymus, hypocalcemia, heart defects
- Velocardiofacial Syndrome: cleft palate, tubular nose, heartdisease
CATCH-22: cardiac, abnormal facial, thymic aplasia, cleft palate, hypocalcemia, chrom 22
Miller-Dieker Syndrome
17p13.3 deletion
Lissencephaly = smooth brain
- developmental delay, hypertelorism, microcephaly
Thalassemias
mutation in synthesis of specific Hb chains
leads to anemia
- see Target RBCs
Sickle Cell anemia
Single mutation Glu6–>Val
- allows for hydrophobic interactions between B-subunits and sickling
- lifespan 120 days to 17 days
- polymerize at low O2 or during illnesses - “crisis”, painful :(
- HbS –> curve shift right
Microcytic Hypochromic Anemia
low MCV, MCH, MCHC
Causes: iron deficiency, thalassemia
Macrocytic anemia
high MCV, vit B12 deficiency
Normocytic normochromic anemia
normal MCV, MCH, MCHC
Causes: anemia of chronic disease, acute blood loss, hemolytic anemia
What virus causes leukemia/lymphomas
HTLV-1 (human T cell lymphotrophic virus)
What virus causes cervical and anogenital carcinomas
HPV
What virus causes Burkitt’s lymphoma
Epstein-Barr Virus (EBV)
What virus causes hepatocellular carcinoma
HCV, HBV
erb B (EGFR)
80% squamous cell carcinoma of lung
80-100% of epithelial tumors of head and neck
50% glioblastomas
Ras
90% pancreas
50% colon, thyroid
Myc
c-Myc: Burkitt’s lymphoma
L-myc: small lung cell carcinoma
n-myc: neuroblastoma
CML
(9;22) abl kinase, bcr regulator
Burkitt’s lymphoma
(8; 14) c-myc, Ig regulator
promyelocytic leukemia
(15;17)–> treat with ATRA
myelomonocytic leukemia
inv(16)
myeloblastic leukemia
(8;21)
Ewing sarcoma
(11;22)
Meningioma
Monosomy 22
Retinoblastoma
del(13)(q14)
alveolar rhabdomyosarcoma
t(2;13)
synovial sarcoma
t(X;18)
FA
chromosome instability syndrome
- inability to repair interstrand DNA crosslinks/translesional synthesis
- lymphomas and leukemias
- hyperpigmentation, triangular face, bone marrow failure
Bloom Syndrome
RECQ helicase mutation, hyperrecombination
- Blm helicase has role in DNA ds break repair
*solid tumors, lymphomas
malar “butterfly” rash
AT
- mutation in ser/thr kinase involved in signal transduction of DNA damage signals to machinery, mutation in ATM gene
- lymphomas
- ability to repair DNA damage from ionizing radiation is impaired
XP
NER pathway
malignancies of skin
