Abnormal Clinical Presentations

Question 1

Zellweger Syndrome

Answer 1

• Mutation in transport proteins of peroxisomes - affects myelin sheath and brain development - is fetal and fatal generally

Question 2

Adrenoleukodystrophy

Answer 2

• disruption in oxidation of long chain fatty acids within peroxisomes - X linked - affects myelin, brain, and adrenals - generally survive about ten

Question 3

Primary Ciliary Dyskinesia

Answer 3

• genetic defects of ciliary proteins result in malformation of skeleton of cilia - causes uncoordinated or absent beating - consequences: dextrocardia, impaired development of skull air sinuses, no mucous removal (meaning recurrent respiratory infections), infertility

Question 4

Ehler’s Danlos Syndrome (EDS)

Answer 4

• Affects 1/5000
• Congenital disorder that is from impaired extracellular modification of collagen, resulting in formation of defective collagen fibers
  
  • Presents with hyperelasticity, loose and unstable joints that dislocate easily, low muscle tone and weakness, various bone abnormalities including vertebra malformations, osteopenia and others.
• Type IV - most serious because of spontaneous ruptures of arteries in the bowel, this reflects abnormal formation of type III collagen
• Type VI - lysl-hydroxylase deficiency (hypermobility and tendency for ocular rupture)
• Type VIIC - due to procollagen N-proteinase deficiency, causing formation of abnoraml thin, irrefular collagen fibrils manifested by marked joint hypermobility

Question 5

Alport Syndrome

Answer 5

• both X linked and autosomal
• affects Type IV collagen fibers
• present with hematuria and may eventually develop ESRD due to renal basal membrane abnormality

Question 6

Scurvy

Answer 6

• Affects the structure of the collagen and is due to Vitamin C deficiency
• major signs are bleeding gums, subcutaneous hemorrhages and poor wound healing
• reflects impaired synthesis of collagen due to deficiency of prolyl and lysl hydroxylase activity

Question 7

I- Cell Disease

Answer 7

• Lysosomal storage disorder
• mutation of mannose-6-phosphate which is the marker tagging a protein to go from trans-Golgi to lysosome.
• Repeated upper respiratory infections, noisy breathing, and a persistent nasaldischarge may also be present. Other symptoms may include growth delays, mental retardation, joint stiffness, deafness, and/or heart disease.

Question 8

Mitochondrial myopathies

Answer 8

• mutations in both nuclear and mitochondrial genes
• maternal inheritance
• presents with proximal muscle weakness, neuro symptoms, lactic acidosis, and cardiomyopathy

Question 9

Pemphigus

Answer 9

• body makes abnormal antibodies to proteins that form desmosomes
• prevents normal adhesion between cells and causes widespread blistering as intraepidermal desmosomes fall apart

Question 10

Marfan’s Syndrome

Answer 10

• autosomal dominant disease affective connective tissue
• due to mutations in the fibrillin gene; missense mutations have been detected in several patients
• most patients are tall and have arachnodactyly (long digits)
• hyperextensibility of the joints
• cardiovascular problems causing weakness of the aortic media, leading to the dilation of the ascening aorta
• concern for mitral valve prolapse

Question 11

chondrosarcoma

Answer 11

• malignant proliferation of cartilage
• cancer has a wide range and slight male predominance
• can develop in any cartilage but is predominate in the pelvis, proximal femur, and proximal humerus
• slow growing tumor
• histologically, they are composed of malignant cells with abundant cartilagnous matrix

Question 12

osteosarcoma

Answer 12

• characterized by the production of osteoid by malignant cells
• second most common primary malignancy of bone (20% of primary bone cancers)
• occur most commonly in teenagers and occur at the sites of the most rapid growth, including the distal femur, proximal tibia, and proximal humerus
• highly metatstatic

Question 13

osteoid osteoma

Answer 13

• small benign tumor that occurs anywhere in the appendicular skeleton or the spine
• causes acute night pains
• histologically, tumors are composed of primary bone with osteoblasts surrounding the osteoid

Question 14

Paget’s disease

Answer 14

• enlarged and deformed bones
• occurs in stages
• initally increased activity of osteoclasts that result in bone resorption
• followed by deposition of irrefular patches of primary bone
• new bone is more fragile and prone to fx
• etiology unknown

Question 15

sirenomelia/caudal dysgenesis

Answer 15

• aka Mermaid syndrome
• insufficient mesoderm is formed in the caudal most region of the embryo
• absent or fused lower limbs, vertebral abnormalities, renal agenesis, and anomalies of teh genital organs
• condition sometimes associated with maternal diabetes

Question 16

situs inversus

Answer 16

left and right organ positons are reversed

Question 17

1) leukocytosis
2) leukopenia
3) normal range of leukocytes

Answer 17

1) > 12,000 leukocytes
2) < 5,000 leukocytes
3) 5,000 to 9,000 leukocytes

Question 18

Lack of well developed cadherins can lead to what?

Answer 18

Metastitic Cancer

Question 19

plural mesothelioma

Answer 19

• aggressive tumor often caused by an exposure to asbestos

Question 20

carcinoma

Answer 20

cancer derived from barrier epithelium

Question 21

adenocarcinoma

Answer 21

cancer derived from glandular epithelium

Question 22

Trisomy 21 (Down Syndrome)

Answer 22

• caused by extra copy of chromosome 21
• growth retardation
• varying degrees of intellectual disability
• craniofacial abnormalities, including upward slanting eyes, epicanthal folds, flat facies, and small ears
• cardic defects
• hypotonia
• increased chance of developing leukemia, infections, thyroid dysfunction, and premature aging
• increased frequency and earlier onset of Alzheimer disease

Question 23

Trisomy 18

Answer 23

• intellectual disability
• congenital heart defects
• low-set ears, flexion of fingers and hands
• micrognathia (tiny chin)
• renal anomalies
• syndactyly and malformations of the skeletal system

Question 24

Trisomy 13

Answer 24

• intellectual disability
• holoprosencephaly (2 hemispheres of forebrain don’t separate correctly)
• congenital heart defects
• deafness
• cleft lip and palate
• eye defects - microphthalmia, anophthalmia, and coloboma

Question 25

Turner Syndrome

Answer 25

• 45, X Karotype
• only monosomy compatible with life
  
  • even then, 98% of all fetuses with the syndrome are spontaneously aborted
• unmistakably female in appearance
• absence of ovaries (gonadal dysgenesis) and short stature

Question 26

Angelman Syndrome

Answer 26

• microdeletion of the long arm of maternal chromosome 15
• intellectual disability, cannot speak
• exhibit poor motor development
• prone to unprovoked and prolonged periods of laughter

Question 27

Prader-Willi Syndrome

Answer 27

• microdeletion of long arm of paternal chromosome 15
• hypotonia
• obesity
• intellectual disability
• hypogonadism and undescended testes

Question 28

Fragile X Syndrome

Answer 28

• FMRI gene on the long arm of the X chromosome
• intellectual disability
• large ears, prominent jaw, and large testes

Question 29

Spina Bifida Occulta

Answer 29

Spinal cord and surrounding meninges remain within vertebral canal

Question 30

Spina Bifida Menigocele

Answer 30

Spinal cord remains in spinal column but surrounding meninges protrude dorsally

Question 31

Spina Bifida Meningomyelocele

Answer 31

Both spinal cord and meninges protrude dorsally

Question 32

Congenital Spondylothesis

Answer 32

primary ossification centers in the neural arch fail to fuse with the centrum’s - pedicles don’t develop; this leaves the centrum prone to becoming displaced

Question 33

craniosyntosis

Answer 33

• sutures in skull develop abnormally, fusing prematurely making a misshapen skull
• negatively impacts development of the brain

Question 34

Williams Syndrome

Answer 34

• deletions in elastin gene
• developmental disorder affecting connective tissue and the CNS
• supravalvular aortic stenosis