Developmental and Genetic Diseases

Coordinator: Diane Persons, M.D.

SUPPLEMENTAL IMAGE DATABASE

PRINCIPLES OF TERATOLOGY:

• Variability
• Specificity for developmental stage
• Specificity for teratogen
• Dose-dependent
• Produces death, growth retardation, malformation or functional impairment

ERRORS OF MORPHOGENESIS

• Agenesis - absence of an organ
• Aplasia - absence of an organ but rudiment present
• Hypoplasia - reduced organ size
• Dysraphic anomalies - failure to fuse (Fig. 6-5)
• Involution failures
• Division failures
• Atresia - incomplete formation of a lumen
• Dysplasia - abnormal organization of cells into tissues
• Ectopia (heterotopia) - organ outside normal anatomic site
• Dystopia - retention of organ at site of development
• Developmental sequence anomaly (Fig. 6-4)
  • Schematic
  • Image

CLINICALLY IMPORTANT MALFORMATIONS:

• Anencephaly
  • Image 1
  • Image 2
• Other neural tube defects:
  • craniorachischisis
  • spina bifida
  • meningocele
  • myelomeningocele
    • Image
    • AFP Graph
• Fetal alcohol syndrome
  • Signs of
  • At different ages
• TORCH complex (Toxoplasmosis, Rubella, CMV, Herpesviruses) (Fig. 6-7)

STRUCTURAL CHROMOSOMAL ABNORMALITIES

• Reciprocal translocations
• Robertsonian translocations
• Chromosomal deletions
• Chromosomal inversions
• Ring chromosomes
• Isochromosomes

NUMERICAL CHROMOSOMAL ABNORMALITIES

• Important terminology:
  • Haploid
  • Diploid
  • Euploid
  • Polyploid
  • Aneuploid
  • Monosomy
  • Trisomy
  • Mosaicism
  • Nondisjunction

SYNDROMES OF THE AUTOSOMAL CHROMOSOMES (Table 6-2)

• Trisomy 21 (Down Syndrome) (Fig. 6-11, Fig. 6-12)
  • Pathology and clinical features:
    • mental retardation
    • cardiac abnormalities
    • skeletal abnormalities
    • GI tract
    • immune system disorders
    • hematologic disorders
    • neurologic disorders
    • Down facies
• Trisomy 18
• Trisomy 13
  • Facies
  • Polydactly
• Deletion 5p-
• Deletion 11p-
• WAGR syndrome
• Deletion 13q-
• Prader-Willi/Angelman

SYNDROMES OF THE SEX CHROMOSOMES

• Klinefelter syndrome (47,XXY) (Fig. 6-14)
  • Image
  • Histology
• Turner syndrome (45, X) (Fig. 6-15)
  • Turner facies
  • Turner syndrome, Streak gonads
  • Turner syndrome, fetal hydrops
  • Turner syndrome, cystic hygroma
• Fragile X

SINGLE-GENE ABNORMALITIES

• Important terms:
  • mendelian trait
  • autosomal gene
  • sex-linked gene
  • dominant phenotypic trait
  • recessive phenotypic trait
  • codominance
  • types of mutations
    • point mutation
    • missense mutation (an example of a point mutation) -
      sickle cell anemia
    • nonsense mutation
    • frameshift mutation
    • large deletion
• Autosomal Dominant Disorders: (Fig. 6-17)
  • Marfan Syndrome (Fig. 6-18)
    • Arachnodactly
    • Aortic dissection
    • Floppy mitral valve
  • Ehlers-Danlos Syndromes
  • Osteogenesis Imperfecta
  • Neurofibromatoses (Fig. 6-19)
    • NF1, von Recklinghausen Disease
    • NF2 central neurofibromatosis
  • Achondroplastic Dwarfism
  • Familial Hypercholesterolemia
• Autosomal Recessive Disorders: (Fig. 6-13, Table 6-4)
  • Cystic Fibrosis (Fig. 6-21, 6-22, 6-23)
    • Molecular mechanism I
    • Molecular mechanism II
    • Lung, gross
    • Pancreas, histology
  • Lysosomal Storage Diseases:
    • Gaucher disease (Fig. 6-25)
      • Splenomegaly
      • Spleen, micro
      • Gaucher cells
    • Tay-Sachs disease (Fig. 6-26)
    • Niemann-Pick Lipidoses
  • Mucopolysaccharidoses
  • Glycogenoses (Von Gierke Disease, Pompe Disease, McArdle Disease)
    • Inborn Errors of Amino Acid Metabolism
      • Phenylketonuria
      • Alcaptonuria (Ochronosis)
      • Albinism
  • X-Linked Disorders
    • X-Linked Dominant Traits (Fig. 6-32)
    • X-Linked Recessive Traits (Fig. 6-33)
      • Muscular Dystrophy (Duchenne-Becker MD) (Fig. 6-34)
      • Hemophilia (Factor VIII deficiency)
      • Fragile X Syndrome

MULTIFACTORIAL INHERITANCE (Table 6-8)

• Cleft Lip and Cleft Palate (Fig. 6-37)

DISEASES OF INFANCY AND CHILDHOOD

• Prematurity and Intrauterine Growth Retardation (Figure 6-39)
• Organ Immaturity (Lungs, Liver, Brain)
• Respiratory Distress Syndrome of the Newborn (Hyaline Membrane Disease) (Figure 6-42)
• Erythroblastosis Fetalis and Neonatal Hemolytic Anemia (Figures 6-44, 6-45)
• Birth Injury
• Sudden Infant Death Syndrome

NEOPLASMS OF INFANCY AND CHILDHOOD

• Benign tumors and tumor-like conditions (Hamartomas, Hemangiomas, Lymphangiomas, Sacrococcygeal Teratomas)
• Malignant tumors
  • Leukemia
  • Neuroblastomas
  • Wilms tumor
    • Gross
    • Micro
  • Retinoblastoma
    • Gross