Congenital disorders

ANATOMY OR SYSTEM AFFECTED: All

DEFINITION: An abnormality present at birth, which may be due to a genetic defect, exposure to a toxic or infectious agent in utero, or a deficiency or lack of a substance necessary for fetal development

CAUSES: Vary; genetic abnormality, exposure to toxic or infectious agent in utero, deficiency or lack of substance necessary for fetal development

SYMPTOMS: Vary from mild to profound, can affect one or more organ systems

DURATION: Often lifelong; some defects correctable through surgery or medication

TREATMENTS: Vary by specific disorder

Causes and Symptoms

Congenital disorders can be the result of genetic factors, environmental exposure, infection during pregnancy, or a deficiency or lack of a substance required for proper fetal development.

Genetic defects include defective genes, extra chromosomal material, and missing chromosomal material. Examples of defects from a single gene include Huntington’s disease, cystic fibrosis, and Tay-Sachs disease. Huntington’s disease is caused by an (inheritance of the gene from one parent will produce the disease). Cystic and Tay-Sachs disease are autosomal recessives (inheritance of the gene from both parents is necessary for expression of the disease). is a progressive and fatal deterioration of the with an onset in middle age. Patients with cystic fibrosis produce excessive in the lungs, pancreas, and other secretory organs. The secretions in the clog respiratory passages, causing damage, and subject the patient to life-threatening infection. Secretions in the prevent the flow of enzymes into the and damage the pancreatic islet cells, resulting in diabetes. Tay-Sachs disease is a fatal disorder in which a fatty substance known as ganglioside G_M2 builds up in tissues and nerve cells in the brain. Even with meticulous medical care, death usually occurs by age four.

In some types of defects caused by recessive genes, the possession of one abnormal gene can be detrimental. One example is sickle cell disease and sickle cell trait, which is an abnormality of the red blood cells. Individuals with two defective genes are much more severely affected than those with one. Some defective genes reside on the sex chromosomes. Females have two X chromosomes, and males have one X and one Y chromosome. The Y chromosome is shorter than the X chromosome and has less genetic material. A defective gene on an X chromosome in the area with no corresponding material on the Y chromosome will always express itself; therefore, these diseases affect males much more frequently than females. An example of an X-linked disease is red-green color blindness, in which individuals cannot distinguish between red and green.

Ethnicity is also a factor in the inheritance of genetic disorders. For example, Tay-Sachs disease is most common among Eastern European Jews (Ashkenazi), is most common among individuals of African descent, and (a blood disease) is most common among people of Mediterranean descent.

A number of congenital disorders are the result of aneuploidy, which is the presence of extra or missing chromosomes. The normal human is twenty-two pairs of and one pair of sex (X and Y). A number of defects due to extra chromosomal material are trisomies. Two examples of trisomies are Down syndrome (trisomy 21) and Edwards syndrome (trisomy 18). Down syndrome is characterized by delayed mental development and physical deformities such as an enlarged tongue, poor muscle tone, and cardiac abnormalities. Trisomy 18 is characterized by profound physical deformities and developmental disabilities; about 50 percent of pregnancies result in live birth; of those, 95 percent of affected individuals die within the first year of life, and those who live rarely survive beyond childhood. Turner syndrome is an example of caused by a missing chromosome. Affected individuals have only one X chromosome and no Y chromosome. They are typically sterile and may have physical characteristics such as short stature and a webbed neck.

Toxic substances ingested by a woman during can affect a developing fetus, often to a much greater extent than the mother. Toxins that can cause congenital disorders include , cocaine, and nicotine. Fetal alcohol syndrome is characterized by delayed mental development, low birth weight, and facial deformities. The syndrome has occurred in infants whose mothers reportedly consumed as little as two drinks per day (one drink is defined as 1.25 ounces of 80 proof liquor, twelve ounces of beer, or six ounces of wine). Infants born of mothers who use cocaine may have low birth weight and disproportionately small heads. They may have learning difficulties; some research suggests that a variety of congenital disorders are prevalent in these children. Mothers who smoke cigarettes during pregnancy are more likely to deliver infants with low birth weights or respiratory problems. Although most congenital disorders resulting from toxins are related to maternal exposure, paternal exposure is a factor in some cases. For example, cocaine use by the father at the time of has been reported to affect the fetus. This is thought to be the result of the lodging of the cocaine on the spermatozoa head; these molecules are passed to the ovum during fertilization. In general, use of a toxic substance increases the risk of fetal loss and birth.

Infectious agents that cause congenital disorders include viruses such as rubella, Human immunodeficiency virus (HIV), and syphilis. A pregnant woman who becomes infected with the rubella virus, particularly during the first (three months), may give birth to an infant with the syndrome. The syndrome is characterized by auditory, cerebral, cardiac, and ophthalmic defects. Symptoms range from mild to severe. If a woman with HIV does not undergo treatment during pregnancy, transmission of the virus to the is likely. Infants born with congenital syphilis may appear healthy at birth; however, they can subsequently develop central nervous system, bone, teeth, and eye disorders. A pregnant woman who contracts Zika, a mosquito-borne virus, in the United States has a 10 percent chance of having a baby with congenital Zika syndrome, a group of birth defects that can include severe microcephaly, neural tube defects, and cerebral palsy.

Poor during pregnancy can likewise result in congenital disorders. Folic acid deficiency has been implicated in the development of defects such as spina bifida, anencephaly, and encephalocele. Spina bifida is caused by failure of the spinal column to close during fetal development. The severity of symptoms depends on the location and size of the defect. Affected infants may have varying degrees of of the as well as problems with bowel and control. Anencephaly is caused by the lack of the formation of a cranium (skull cap); as a result, the does not form at all or in major part. This disorder is always fatal. The longest-lived infant survived to twenty-eight months without life-sustaining interventions, while another child lived for 2.5 years on a ventilator. An encephalocele is a skull defect that exposes a portion of the brain. This disorder may be fatal or result in varying degrees of developmental disability.

Treatment and Therapy

As is the case with all disorders, prevention is preferable to treatment. Avoidance of harmful substances (mind-altering drugs, alcohol, and tobacco) during pregnancy is essential, and adequate nutrition, including vitamin supplements, is extremely important. Exposure to infectious agents (rubella, HIV, syphilis) should be avoided. Certain medications can increase the risk of congenital disorders, including isotretinoin and etretinate, used for the treatment of , and phenytoin and carbamazepine, used to treat epilepsy. Any woman who is pregnant or contemplating pregnancy should consult a health care professional in regard to any medication, prescription or nonprescription.

Screening tests such as the are blood tests that can screen for genetic abnormalities. Chorionic villus sampling (CVS) and amniocentesis can definitively diagnose genetic abnormalities that cause disorders such as Down syndrome and 18. Single-gene defects can also be diagnosed with CVS or amniocentesis, particularly when a family history of the defect is present. Prenatal diagnosis allows parents the ability to choose whether to continue with a pregnancy. If they opt to continue with the pregnancy, it gives them time to seek counseling and join support groups to help them cope with caring for a child with a congenital disorder.

Treatment for congenital disorders ranges from nonexistent to complete. For example, anencephaly has no known treatment. Phenylketonuria (PKU) , a metabolic defect that leads to developmental disabilities, is caused by an inability to metabolize the amino acid phenylalanine. As such, a special low-phenylalanine diet can markedly reduce progression of the disease. Surgery can correct some congenital disorders, such as cardiac defects related to Down syndrome and spinal defects associated with spina bifida.

Advances in medical science and supportive therapy have greatly improved the longevity of patients with genetic disorders. For example, for centuries, many children with died in childhood. However, according to the Cystic Fibrosis Foundation, by the early twenty-first century, many individuals with access to medical treatment were able to live well into adulthood.

Perspective and Prospects

Genetic disorders have been recognized for centuries; however, the genetic basis was not understood until the latter half of the twentieth century. Down syndrome and cystic fibrosis are two typical examples. English physician John Down noted that Down syndrome was a specific type of mental disability with distinct physical features. For centuries, the foreheads of children with cystic fibrosis were licked; if a salty taste was noted, the child was deemed to be bewitched and expected to die soon. It was not until the 1990s that the mutated gene that causes the disease was identified.

In addition to Down syndrome and cystic fibrosis, rapid progress has been made in the past decades in regard to genetic abnormalities. The locations of defective genes have been mapped, and (different forms of a gene) have been identified. Research into the treatment of congenital disorders caused by genetic abnormalities is ongoing. Currently, treatment is mainly limited to surgical correction of defects (correction of a cardiac abnormality in an individual with Down syndrome), medical therapy (enzyme therapy for an individual with cystic fibrosis), and supportive care (pulmonary therapy to loosen secretions in an individual with cystic fibrosis). The most promising treatment for specific gene defects rests in the field of research. Single-gene defects may be curable via gene therapy in the near future. To date, most of the studies have been animal or in vitro (laboratory) studies.

The outlook is much poorer for trisomies, which involve a significant amount of extra chromosomal material. The outlook is extremely poor for severe disorders such as trisomy 18 and virtually hopeless for disorders such as anencephaly. In the case of anencephaly, the best option at present is early diagnosis via CVS or and pregnancy termination.

There now exists an increased public awareness of the impact of exposure to toxins and infections on pregnancy. This increased awareness has the potential to reduce the incidence of these preventable disorders. For example, awareness of the benefits of folic acid can reduce the incidence of neural tube defects. Aggressive therapy for children with a disorder caused by exposure to a can sometimes reverse the damage. For example, speech therapy and other behavioral support can reverse central nervous disorders resulting from congenital cocaine exposure. The therapy must be initiated promptly when symptoms are recognized, while the developing brain is in its formative phase. Therapy is most effective before the age of five.

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