In some cases retardation can be directly traced to a chromosomal defect, to heredity, or to another genetic deficiency. Each individual is born with 23 pairs of chromosomes, on which the physical build and appearance of the person is coded. Each parent provides 23 chromosomes. These match up at conception, and the parents’ features are passed on to the children. Sometimes an extra chromosome is accidentally present. Other times dominant or recessive traits are passed on to the child. Sometimes there are disorders in the way the body functions, which develop from unknown genetic involvement but which suggest deficiencies in genetic makeup.
Down’s syndrome occurs when an extra chromosome in the twenty-first pair is found. While there is no known reason why this occurs, and either parent may contribute the extra chromosome, it is known that the chance of giving birth to a Down’s child increases with the age of the mother. Down’s syndrome results in a moderate to severe level of retardation. It is characterized by slanting eyes, a flattened and wide nose, and small ears, tongue, and mouth.
Four other chromosome defects produce recognizable syndromes. The cat-cry syndrome results from a missing part of the fifth chromosome. Due to vocal chord abnormalities the infant gives a characteristic cat cry. Severe retardation and numerous other physical complications are present. Trisomy 13, occurring once in 5,000 births, refers to an extra chromosome in the thirteenth pair. It is characterized by low-set ears, cleft palate, cleft lip, sloping forehead, extra fingers, retardation, and often minor seizures. Of these children only 18% survive the first year; poor growth is evidenced. Trisomy 18, with an extra chromosome in pair 18, occurs about once in 3,000 births. Around 80% are females and only 10% survive the first year. Many die before birth. Low birth weight, incomplete development of skeletal muscle, cardiac defects, severe retardation, and numerous other abnormalities are seen. Trisomy 22 is rare and is characterized by retardation, small head, slanted eyes, slow and delayed growth, and heart defects.
Several syndromes are related to abnormalities in the chromosomes determining the sex of the child. These chromosomes, called X and Y, produce a female when the pair is XX and a male when the pair is XY. If only one X occurs rather than a pair, a girl is born with Turner’s syndrome. She is short of stature, has no sexual organs, and lacks sexual development. While 95 to 98% of the fetuses with Turner’s syndrome fail to survive to birth, some girls may not be diagnosed until adolescence, when the failure to develop sexually is noted. Mild retardation may be present, but more notable is a defect in space-form perception.
Klinefelter’s syndrome is found in males when the sex chromosome consists of XXY. Retardation is not usually characteristic, although 25 to 50% of reported cases had subnormal intelligence. In some cases as many as five X chromosomes have been found with a Y. The male with more than two X chromosomes has a higher risk of significant mental retardation.
The XYY male appears to be prevalent in the population with only slight intellectual retardation noted. At one point it was thought that this chromosome combination is associated with criminality, since reports of numerous XYY men in prisons were published. Later studies failed to verify this, but some lowered language ability was found.
Many syndromes are inherited in simple Mendelian fashion. When one parent passes on a dominant gene to the child, the trait carried by the gene will always occur. Recessive traits require a similar gene from both parents before the trait occurs. While they are rare and isolated, several syndromes resulting in mental retardation have been associated with dominant and recessive genes.
Most dominant gene syndromes that lead to severe retardation produce death before birth. Four syndromes are related to dominant gene transmission.
Tuberous sclerosis is a disease manifested by severe mental retardation, seizures, and a peculiar skin condition characterized by butterfly-shaped reddish-yellow tumors, usually on the cheeks alongside the nose. These tumors are nonmalignant and later may be found in the brain or other organs of the body. They may not be observable, and the disease may not be recognized until the child develops seizures around age 3 or facial skin tumors around age 5.
Neurofibromatosis is a condition characterized by light brown patches on the skin, the color of milky coffee (café-au-lait spots), and by tumors on the nerves and in the skin. The tumors may be tiny or grotesque overgrowths. At least six such spots must be present before a diagnosis is made, since normal people may have one or a few spots. Mental retardation and epilepsy occur in about 10% of cases, possibly due to tumors in the brain.
Sturge-Weber syndrome displays a growth the color of port wine formed by blood vessels on the face, usually in the area of the trigeminal nerve on the cheek or forehead. Similar malformations of the blood vessels within the meninges covering of the brain can give rise to mental retardation and seizures.
Myotonic dystrophy affects the whole body. Cataracts, testicular atrophy, frontal baldness, muscle spasms, and muscle wasting are evident. Considerable behavioral abnormality is seen in adults, and retardation may be present. In most cases the child has received the dominant gene from the mother. This suggests that a combination of an abnormal gene and an abnormal prenatal environment is necessary for very early onset.
There are thousands of recessive genes, many of which are harmless, such as the one producing blue eyes. Others are serious, such as the one producing cystic fibrosis. Many recessive disorders that involve retardation produce specific metabolic deficiencies. Metabolism refers to the ability of the body to break down and use particular foods or release energy for use. Some of the more common metabolic disorders are discussed according to the type of deficiency affected. Several nonmetabolic disorders related to recessive genes will also be covered.
Disorders of protein and amino acid metabolism include the much researched phenylketonuria (PKU). PKU is the inability of the body to oxidize the amino acid phenylalanine to tyrosine. As a result, untreated individuals are severely retarded and often are unable to walk or talk. Besides being bedridden, PKU persons are often restless, jerky, and fearful. They may be shy, restless, and anxious, or destructive with noisy psychotic episodes, irritable, and have uncontrollable temper tantrums. Since the 1930s considerable research has demonstrated that most of the severe symptoms can be prevented with a diet that restricts phenylalanine. Prompt diagnosis is essential, including identifying the parent carrier and screening newborn infants. Dietary control can reverse biochemical abnormalities, but structural defects and brain damage cannot be reversed.
Menkes disease, or the maple syrup disease, refers to the inability to metabolize the amino acid leucine. The disease gets its name from the distinct maple syrup odor of the urine. Dietary control prevents many severe symptoms. If it is untreated, the disease is usually fatal by age 2.
Histidinemia is a block in the metabolism of histidine. Abnormal speech patterns or retardation in language development are seen. Dietary control is used. There is some question in the literature about the relationship of this deficiency to retardation.
Disorders of carbohydrate metabolism, represented chiefly by galactosemia, involve the inability to break down sugars into usable parts. When lactose, the primary sugar in milk, is converted into glucose and galactose, the body must convert galactose into a glucose substance. If the child’s body is unable to do this, life-threatening symptoms develop from a milk diet. Jaundice, vomiting, cataracts, malnutrition, and potentially fatal susceptibility to infection occur. Strict dietary control and prompt identification are necessary to prevent severe damage and death.
When the complex carbohydrate substances are not properly broken down, and the resultant mucopolysaccarides are stored, severe physical and mental retardation occurs. Hurler syndrome children are dwarfed, deaf, have clouded corneas, widely spaced teeth, short neck, a large and bulging head, and several internal problems with liver, spleen, and hernias. These children tend to be friendly and affectionate. Hunter syndrome is less severe but includes gargoyle appearance, stiff joints, dwarfing, and enlarged liver and spleen. These children are characteristically hyperactive and hard to manage.
Several disorders have been identified related to the inability of the body to metabolize complex fats and lipids. The most common of these disorders is Tay-Sachs disease, named after a British ophthalmologist, Warren Tay, and an American neurologist, Bernard Sachs, who described cases of this disease in the 1880s. This recessive trait is frequent among Ashkenazic Jews, of whom 1 in 30 is a carrier. In all other groups 1 in 300 is a carrier. The presence of this disease can be detected with blood tests or amniocentesis. It usually begins insidiously by 6 months, with listlessness, weakness, hypersensitivity to sounds, and visual difficulties developing. Blindness occurs and death is frequent by 3 years. A partial deficiency of the same enzyme has been reported with less severe effects.
A final recessive disorder is microcephaly, or a small head. The skull is unusually tiny. Severe retardation and blindness are prominent.