Patau Syndrome

Patau syndrome, also called trisomy 13, is a congenital (present at birth) disorder associated with the presence of an extra copy of chromosome 13. The extra chromosome 13 causes numerous physical and mental abnormalities, especially heart defects. Patau syndrome is named for Dr. Klaus Patau, who reported the syndrome and its association with trisomy in 1960.

Description

Children normally inherit 23 chromosomes from each parent, for a total of 46 chromosomes. A typical human being has 46 chromosomes: 22 pairs of non-sex linked chromosomes and one pair of sex-linked chromosomes, that determine that child's sex. Sometimes a child may end up with more than 46 chromosomes because of problems with the father's sperm or the mother's egg; or, because of mutations that occurred after the sperm and the egg fused to form the embryo (conception).

Normally, there are two copies of each of the 23 chromosomes: one from each parent. A condition called trisomy occurs when three, instead of two, copies of a chromosome are present in a developing human embryo. An extra copy of a particular chromosome can come either from the egg or sperm, or because of mutations that occur after conception.

The most well-known trisomy-related disorder is Down syndrome (trisomy 21), in which the developing embryo has an extra copy of chromosome 21. Patau syndrome is trisomy 13, in which the developing embryo has three copies of chromosome 13.

An extra copy of chromosome 13 is not the only cause of Patau syndrome. Other changes in chromosome 13, such as mispositioning (translocation), can also result in the characteristics classified as Patau syndrome. In these cases, an error occurs that causes a portion of chromosome 13 to be exchanged for a portion of another chromosome. There is no production of extra chromosomes; but, a portion of each affected chromosome is "misplaced" (translocated) to another chromosome.

Patau syndrome causes serious physical and mental abnormalities including: heart defects; incomplete brain development; unusual facial features such as a sloping forehead, a smaller than average head (microcephaly), small or missing eyes, low set ears, and cleft palate or hare lip; extra fingers and toes (polydactyly); abnormal genitalia; spinal defects; seizures; gastrointestinal hernias, particularly at the navel (omphalocele); and mental retardation. Due to the severity of these conditions, fewer than 20% of those affected with Patau syndrome survive beyond infancy.

Genetic profile

When an extra copy (trisomy) of a chromosome is made, it may either be a total trisomy (in which an extra copy of the entire chromosome is made), or partial trisomy (in which only one part of the chromosome is made an extra time).

In most cases of trisomy, errors in chromosome duplication occur at conception because of problems with the egg or the sperm that are coming together to produce an offspring. In these cases, every cell in the body of the offspring has an extra copy of the affected chromosome. However, errors in chromosome duplication may also occur during the rapid cell division that takes place immediately after conception. In these cases, only some cells of the body have the extra chromosome error. The condition in which only some of the cells in the body have the extra chromosome is called mosaicism.

Seventy-five to 80 percent of the cases of Patau syndrome are caused by a trisomy of chromosome 13. Some of these cases are the result of a total trisomy, while others are the result of a partial trisomy. Partial trisomy generally causes less severe physical symptoms than full trisomy. Ten percent of these cases are of the mosaic type, in which only some of the body's cells have the extra chromosome. The physical symptoms of the mosaic form of Patau syndrome depends on the number and type of cells that carry the trisomy.

Most cases of trisomy are not passed on from one generation to the next. Usually they result from a malfunction in the cell division (mitosis) that occurs after conception. At least 75% of the cases of Patau syndrome are caused by errors in chromosome replication that occur after conception. The remaining 25% are caused by the inheritance of translocations of chromosome 13 with other chromosomes within the parental chromosomes. In these cases, a portion of another chromosome switches places with a portion of chromosome 13. This leads to errors in the genes on both chromosome 13 and the chromosome from which the translocated portion originated.

Patau syndrome occurs in approximately one in 10,000 live births. In many cases, spontaneous abortion (miscarriage) occurs and the fetus does not survive to term. In other cases, the affected individual is stillborn. As appears to be the case in all trisonomies, the risks of Patau syndrome seem to increase with the mother's age, particularly if she is over 30 when pregnant. Male and female children are equally affected, and the syndrome occurs in all races.

Causes and symptoms

The severity and symptoms of Patau syndrome vary with the type of chromosomal anomaly, from extremely serious conditions to nearly normal appearance and functioning. Full trisomy 13, which is present in the majority of the cases, results in the most severe and numerous internal and external abnormalities. Commonly, the fore-brain fails to divide into lobes or hemispheres (holoprosencephaly) and the entire head is unusually small (microcephaly). The spinal cord may protrude through a defect in the vertebrae of the spinal column (myelomeningocele). Children who survive infancy have profound mental retardation and may experience seizures.

Incomplete development of the optic (sight) and olfactory (smell) nerves often accompany the brain defects described above. The eyes may be unusually small (microphthalmia) or one eye may be absent (anophthalmia). The eyes are sometimes set close together (hypotelorism) or even fused into a single structure. Incomplete development of any structures in the eye (coloboma) or failure of the retina to develop properly (retinal dysplasia) will also produce vision problems. Patau syndrome affected individuals may be born either partially or totally deaf and many are subject to recurring ear infections.

The facial features of many Patau syndrome affected individuals appear flattened. The ears are generally malformed and lowset. Frequently, a child with trisomy 13 has a cleft lip, a cleft palate, or both. Other physical characteristics include loose folds of skin at the back of the neck, extra fingers or toes (polydactyly), permanently flexed (closed) fingers (camptodactyly), noticeably prominent heels, "rocker-bottom foot," and missing ribs. Genital malformations are common in individuals affected with Patau syndrome and include undescended testicles (cryptorchidism), an abnormally developed scrotum, and ambiguous genitalia in males, or an abnormally formed uterus (bicornuate uterus) in females.

In nearly all cases, Patau syndrome affected infants have respiratory difficulties and heart defects, including atrial and ventricular septal defects (holes between chambers of the heart); malformed ducts that cause abnormal direction of blood flow (patent ductus arteriosus); holes in the valves of the lungs and the heart (pulmonary and aortic valves); and misplacement of the heart in the right, rather than the left, side of the chest (dextrocardia). The kidneys and gastrointestinal system may also be affected with cysts similar to those seen in polycystic kidney disease. These defects are frequently severe and life-threatening.

Partial trisomy of the distal segment of chromosome 13 results in generally less severe, but still serious, symptoms and a distinctive facial appearance including a short upturned nose, a longer than usual area between the nose and upper lip (philtrum), bushy eyebrows, and tumors made up of blood capillaries on the forehead (frontal capillary hemangiomata). Partial trisomy of the proximal segment of chromosome 13 is much less likely to be fatal and has been associated with a variety of facial features including a large nose, a short upper lip, and a receding jaw. Both forms of partial trisomy also result in severe mental retardation.

Beyond one month of age, other symptoms that are seen in individuals with Patau syndrome are: feeding difficulties and constipation, reflux disease, slow growth rates, curvature of the spine (scoliosis), irritability, sensitivity to sunlight, low muscle tone, high blood pressure, sinus infections, urinary tract infections, and ear and eye infections.

Diagnosis

Patau syndrome is detectable during pregnancy through the use of ultrasound imaging, amniocentesis, and chorionic villus sampling (CVS). At birth, the newborn's numerous malformations indicate a possible chromosomal abnormality. Trisomy 13 is confirmed by examining the infant's chromosomal pattern through karyotyping or another procedure. Karyotyping involves the separation and isolation of the chromosomes present in cells taken from an individual. These cells are generally extracted from cells found in a blood sample. The 22 non-sex linked chromosomes are identified by size, from largest to smallest, as chromosomes 1 through 22. The sex determining chromosomes are also identified. Patau syndrome is confirmed by the presence of three, rather than the normal two, copies of the thirteenth largest chromosome.

Treatment and management

Some infants born with Patau syndrome have severe and incurable birth defects. However, children with better prognoses require medical treatment to correct structural abnormalities and associated complications. For feeding problems, special formulas, positions, and techniques may be used. Tube feeding or the placement of a gastric tube (gastrostomy) may be required. Structural abnormalities such as cleft lip and cleft palate can be corrected through surgery. Special diets, hearing aids, and vision aids can be used to mitigate the symptoms of Patau syndrome. Physical therapy, speech therapy, and other types of developmental therapy will help the child reach his or her potential.

Since the translocation form of Patau syndrome is genetically transmitted, genetic counseling for the parents should be part of the management of the disease.

Prognosis

Approximately 45% of trisomy 13 babies die within their first month of life; up to 70% in the first six months; and over 70% by one year of age. Survival to adulthood is very rare. Only one adult is known to have survived to age 33.

Most survivors have profound mental and physical disabilities; however, the capacity for learning in children with Patau syndrome varies from case to case. Older children may be able to walk with or without a walker. They may also be able to understand words and phrases, follow simple commands, use a few words or signs, and recognize and interact with others.