Dysmorphology

• Definition: The study of morphological developmental abnormalities as seen in many syndromes of genetic or environmental origin.
  
• Congenital anomalies - represent a significant proportion of clinically significant disorders seen in newborns and older children.
  
  • Of almost 70,000 infants, liveborn or stillborn in one study, 2.3 percent had at least one major structural malformation.
    
  • Additional anomalies can be recognized after birth.
    Incidence -
    
    • about 6 percent in 2 year olds.
      
    • about 8 percent in 5 year olds.
      
• Terms used to describe defects:
  
  • Anomaly - structural abnormality of any type. Four types of clinically significant anomalies are defined:
    
    • Malformation - morphological defect resulting from an intrinsically abnormal developmental process. These include chromosomal disorders, single gene malformations such as achondroplasia and Marfan syndrome.
      
    • Disruption - morphological defect resulting from breakdown of, or interference with an originally normal developmental process. Examples include amniotic bands or limb reduction defects caused by vascular anomalies.
      
    • Deformation - an abnormality in form or position of a body part caused by nondisruptive mechanical force. Deformations may be caused by mechanical constraint (uterine size, leiomyomas, septate uterus) or to defects in fetus itself (neurological or connective tissue).
      
    • Dysplasia - abnormal organization of cells into tissues and its morphological consequence. An example includes ectodermal dysplasia (abnormalities of tissues derived from ectoderm -- skin, teeth, nails, hair).
      
  • Sequence - a structural defect or mechanical factor can lead to multiple secondary effects (Pierce Robin sequence, oligohydramnios sequence)
    
  • Syndrome - multiple anomalies are thought to be independent rather than sequential, although they have a single basic cause (Down Syndrome, Apert Syndrome)
    
• Teratogens
  
  • Definition - any agent that can produce a malformation or raise the population incidence of a malformation.
    Most known teratogens are infectious agents, radiations or drugs.
    
  • Factors influencing teratogenic effects
    
    • Time of exposure - It is most important to know the precise gestational age during which exposure occurred. Often an ultrasound examination helps to establish the gestational age. Teratogens exert their effect when differentiation and morphogenesis are at their peak. In rubella embryopathy, the malformations produced at an early stage (before the ith week of pregnancy) are much more severe than those produced after the 14th week.
      
    • Dosage - There are few studies in humans on dose-response effects. However, in diabetes Mellities, it is well-accepted that women with better glycemic control during the first trimester of pregnancy have a lower risk of birth defects when compared to women with poor glycemic control. How the mother metabolizes drugs or other substances may play a role in determining serum levels and fetal exposure.
      
    • Genotype of the fetus - There are several examples of this effect in humans. For example, phenytoin, an anti-convulsant medication is teratogenic. It induces a syndrome of craniofacial anomalies, prenatal and postnatal growth abnormalities, mental retardation and limb defects (fetal hydantoin syndrome).
      
    • Fetal hydantoin syndrome - teratogenicity is associated with elevated levels of oxidative metabolites that are normally eliminated by the enzyme epoxide hydrolase, which appears to be a polymorphic enzyme with low-activity and high-activity alleles. About 5-10 percent of exposed infants have the full-blown syndrome, about one third have some deleterious effects and more than one half are unaffected. Identification of at risk fetuses may help us better manage these pregnancies.
      
    • Maternal Genotype - An example of this effect is the increased risk of microcephaly, congenital heart defects and growth abnormalities in the offspring of mothers with phenyketonuria(PKU) that is untreated.
      
  • Other Information:
    
    • Illinois Teratogen Information Service
      
    • Clinical Teratology Web Site