Congenital malformations are structural abnormalities due to faulty development, present at birth, and are among the major causes of prenatal, perinatal and infant mortality and morbidity. They include gross and microscopic malformations, inborn errors of metabolism, mental retardation and cellular and molecular abnormalities. About 2–3% of newborns have a single major malformation, and 0.7% have multiple major defects (Norman et al. 1995; Opitz and Wilson 1997; Aicardi 1998; Volpe 2001a).
In 40 to 60% of persons with birth defects, the cause is unknown. Genetic factors, such as chromosome abnormalities and mutant genes, account for approximately 15%. Environmental factors produce approximately 10%. Combination of genetic and environmental influences (multifactorial inheritance) produces 20 to 25%; and twinning causes 0.5 to 1%.
Congenital Anomaly (CA) is an anomaly that affects a body part or physiologic function and is present at birth.
Congenital Malformation is a congenital anomaly of the structure of some body part.
Birth Defect or Congenital Disorder are nearly synonyms for the term Congenital Anomaly.
Chromosomal Aberrations are the numerical or structural abnormalities of the karyotype.
Genetic Disorders are the conditions caused by the mutation of the gene(s).
Malformation is caused by an abnormal development of the organ or tissue that is abnormal from the beginning.
Disruption is caused by destructive process, that affects an organ or tissue that started to develop normally.
Deformation is caused by an abnormal physical force that damages healthy organ or tissue.
Dysplasia is caused by an abnormal organization of the cells in the organ or tissue.
Association of anomalies
Isolated anomaly: an anomaly that is not associated with any other conditions (e.g. isolated polydactyl).
Sequence: multiple anomalies that result from the pathologic cascade caused by a primary insult (e.g. Potter‘s sequence).
Association: selected congenital anomalies that tend to develop all together – in an association (e.g. VATER association).
Syndrome: complex of phenotypic traits (anomalies) that are typical for defined clinical diagnosis (e.g. Down syndrome).
1. Structural: Where external form or structure is abnormal.
2. Functional: Where the function of the organ is affected. In functional anomaly the defect can be at cellular level, where a particular enzyme may not be formed normally, e.g. in hemophilia a particular factor essential for clotting is absent.
3. Metabolic: Where there can be defect in metabolism because of absence or defect in one or more enzymes
Teratogene is an agent that is able to affect normal ontogenetic development and lead to a congenital anomaly. Teratogens cause congenital anomalies.
Mutagene is an agent that is able to affect the genetic information on the level of DNA or on the level of chromosomes. Mutagens cause mutations. Some mutagens are also teratogens. However, not all teratogens are mutagens.
• Maternal age over 35 years (chromosomal syndromes risk increases with age of the mother at conception)
• Healthy carriers’ genitors of balanced chromosomal anomalies
• Family history of chromosomal anomalies (eg. DS)
• Congenital genetic disease husband (Duchenne muscular dystrophy, hemophilia, diseases linked to chromosome X)
• Reproductive history (fetus with chromosomal abnormalities, birth defects, miscarriages early newborn deaths)
• Women exposed to radiation, consuming potentially teratogenic drugs, carriers of metabolic disease (diabetes)
The main goal is to prevent anomaly or malformation before they develop (that means before conception or during pregnancy). The women should avoid the pregnancy in very low or very high age. The pregnancy should be planned. The parents should avoid any contact with mutagens or teratogens. No stress, smoking, drugs and alcohol during pregnancy.
Clinical geneticist should be consulted in advance – if necessary (repeated abortions, congenital anomalies in family, genetic diseases). Good compensation of mother‘s diseases (DM, PKU etc.)Supplementation with folic acid
The main goal is to prevent the birth of a child with a congenital anomaly. However, the termination itself is not a prevention. We can terminate the pregnancy in order to prevent such a birth. However, the termination may not be legal in each country.
In the Czech Republic it is legal to terminate the pregnancy because of severe genetic reasons till 24th week of pregnancy. Prenatal diagnosis is therefore very important, because we need the best information available about the condition of the fetus. If a severe condition is diagnosed, we may offer termination of pregnancy, prenatal therapy or special treatment in perinatologic period.