Patau syndrome (Trisomy 13)

Definitions & Key takeaways

Patau syndrome, also known as trisomy 13, is a chromosomal disorder where a person inherits three copies of chromosome 13, usually as a result of meiotic nondisjunction.

Patau syndrome is characterized by a wide range of physical and mental abnormalities. Symptoms may include craniofacial defects, heart defects, brain malformations, intellectual disability, and developmental delays. There is no cure for Patau syndrome, treatment focuses on managing symptoms and providing supportive care.

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Patau syndrome is a chromosomal disorder where a person inherits an extra copy of chromosome 13, or a part of it. So instead of having two, they have three copies of chromosome 13, and so Patau syndrome is also known as trisomy 13.
Patau syndrome is named after Dr. Klaus Patau, who first described the chromosomal nature of the syndrome.
All right, our DNA is like this humongous blueprint of information on how to make a human. Usually this massive document is packaged up nicely into storage bins called chromosomes.
Actually, we usually have 46 chromosomes that we use to neatly organize all our information, depending on how you define organize.
Each of the 46 chromosomes is actually part of a pair of chromosomes, since you get one from each parent, so 23 pairs. If you wanted to make another human, first you’d have to find someone that feels the same way, and then you both contribute half of your chromosomes, so one from each pair, right?
Fifty-fifty. Now, what if someone contributes one too many?
Say Dad contributes 23 and Mom contributes 24, is that possible? Yes, and it’s the basis of trisomies, in other words, having three copies of a particular chromosome.
Trisomy 13, or Patau syndrome, is the least common, but most severe trisomy in live births. Alright, so in order to package up half the chromosomes into either a sperm cell or an egg cell, you actually start with a single cell that has 46 chromosomes, let’s just say we’re making an egg cell for the mother.
I’m just going to show one pair of chromosomes, but remember that all 23 pairs do this. So the process of meiosis starts, which is what produces our sex cells, and the chromosomes replicate, and so now they’re sort of shaped like an ‘X’—even though there are two copies of DNA here, we still say it’s one chromosome since they’re hooked together in the middle by this thing called a centromere.
OK, then the cell then splits in two, and pulls apart the paired chromosomes, so in each of these cells, you now have 23 chromosomes.
Now the two copies of the chromosome get pulled apart, and the cells split again, which means four cells, each cell still with 23 chromosomes.
Now these are ready to pair up with a sperm cell from dad that has 23 chromosomes as well, totaling 46 chromosomes, and voila–nine months down the road you’ve got yourself a baby.
OK, let’s now see how someone can end up with three copies of chromosome 13 instead of two. Well, with Patau syndrome, or trisomy 13, a process called nondisjunction accounts for most of the cases.
Non-disjunction means the chromosomes don’t split apart. If the chromosomes in this first step don’t split apart, then one cell ends up with both chromosomes, and the other gets none.
Then the final result is 2 cells with an extra chromosome, and two cells missing a chromosome. Nondisjunction can also happen in the second step, so the first steps have no problems, and both cells have a chromosome, but if they don’t split apart in the second step, then the final result is one cell with an extra chromosome, one cell missing a chromosome, and two with the correct number of chromosomes.
Now, if a sperm cell combines with any of these eggs that have a duplicate of chromosome 13, then the combined cell will have three chromosome 13s, or trisomy 13.
Apart from nondisjunction, Robertsonian translocation accounts for a small percentage of trisomy 13 cases. Translocation means that a part of one chromosome switches places with a part from another chromosome.
One of these chromosomes needs to be chromosome 13, but the other can be any other chromosome. In this example, the long arm of chromosome 13 translocates over to chromosome 14, and you end up with one hybrid that has both long arms, and one hybrid with both short arms.
This guy with the short arms carries nonessential genes, or genes that are not essential to survive and is typically lost by the end of meiosis.
All right, let’s say these cells replicate and split into one with both normal chromosomes, and one with a chromosome with only long arms and one with only short arms, in which case after splitting again you’d have two normal cells, and two cells with a big guy, since we lost the little guy along the way.
So after contributing the other parent’s DNA, you’ve got two normal cases. These two cases are “balanced carriers”, and we say they’re balanced because they’ve got both long arms, and so most of the genes are still here.
So balanced carriers usually don’t have any symptoms. OK, now let’s say the normal chromosome 14 ends up with the short arm, and normal chromosome 13 with the long arm.
Now you get two cells with the normal and long-arm, and two cells with the normal and short arm, which remember is usually lost.
So these ones have one extra chromosome 13, since the long arms carry most of the genetic material for both chromosomes 14 and 13, and these ones are missing chromosomes.
Now combine these with the other parent’s again, and it results in two trisomy 13 cells, and two monosomy 13 cells, since it’s missing a chromosome 13.
If this process was switched such that chromosome 14 ended up with the long chromosome first, then you’d ultimately end up with trisomy 14 and monosomy 14.
So out of the 12 possibilities, two end up being trisomy 13, and they will have all the symptoms. Finally, about 1% of patients are mosaic, meaning their cells are mixed, and some have 46 chromosomes and some have 47.
So after conception you’ve got this one cell, called the zygote, that needs to develop into a human and so it has to divide, over and over again, producing every kind of cell in the body.
Each of these divisions is called mitosis. Nondisjunction of chromosome 13 can also happen during mitosis, in which case, you’d end up with one cell that has an extra chromosome 13, and one without, so one with 47 total chromosomes, and one with 45.
The cell with 45 chromosomes isn’t able to survive, but the one with 47 does survive, and continues to replicate and produce more cells with 47 chromosomes.
Mosaic patients usually have less severe symptoms when compared to patients who have trisomy 13 in every cell in their body.
Alright, now having an extra chromosome 13 leads to overexpression of the genes on that chromosome, which disrupts the normal development of all types of cells, causing multiple organ defects.
Babies with Patau syndrome have microcephaly, or a very small head; and holoprosencephaly, or a failure of the prosencephalon, which is the forebrain of the embryo, to divide into the two hemispheres.
Another common defect is meningomyelocele, which is a severe type of spina bifida that occurs when the spinal cord and the surrounding meninges protrude out of an opening in the bony vertebrae, and are held together by a sack of skin that pouches out from the back.
These babies will also experience developmental delays and will end up with severe intellectual disability. Problems in other organ systems include gastrointestinal problems, like an omphalocele, which is when some of the bowels herniate out into the umbilical cord; heart problems, like septal defects; and renal problems, like polycystic kidney disease, which is when the kidneys become filled with hundreds of cysts, or fluid-filled sacs.
A major risk factor for Patau syndrome is advancing maternal age, or the age of the mother. Another important risk factor is family history, or having another baby with Patau syndrome in the family.
Now most of the babies with Patau syndrome die before birth. But even if they do survive, they usually die shortly after birth, with a median survival time of three days, and only about 5% of the babies with Patau syndrome survive past six months of life.
There is a long list of dysmorphic features as well, like cutis aplasia, where cutis means skin and aplasia means failure to develop, and so in babies with Patau syndrome we can find scalp lesions with the absence of skin.
Other characteristics include microphthalmia, or small eyes; polydactyly, where poly means many and dactyly is for fingers or toes; cleft lip and palate, which are openings in the upper lip or roof of the mouth, and rocker bottom feet, which is when the soles of the feet are rounded and smooth like the bottom of a rocking chair.
More severe defects include cyclopia, named after the Cyclops, a giant from Greek mythology that has a single eye at the center of his forehead.
This can occur as a result of the holoprosencephaly because when the forebrain of the embryo fails to divide into the two brain hemispheres, the two orbits don’t divide into two cavities either, remaining in a single cavity.
Another defect is that their nose might be missing or replaced by a proboscis, which is an elongated organ like an elephant’s trunk.
OK, now during pregnancy, clinicians can perform screening tests like a prenatal ultrasound, where they look for any abnormalities of the baby, including increased nuchal translucency.
Certain serum markers also suggest that a baby might have Patau syndrome. During the first trimester, human chorionic gonadotropin, or HCG; and pregnancy-associated plasma protein A, or PAPP-A, are on average lower when compared to unaffected pregnancies.
However, during the second trimester, alpha-fetoprotein or AFP; unconjugated estriol or uE3; inhibin; and also HCG, are all normal, which can be misleading.
Diagnosis can be confirmed with karyotyping, which visualizes each chromosome and can be done before birth with an amniocentesis, or at any time after birth with a blood test.
Now, because Patau syndrome is due to a chromosomal problem, there is no known cure, and so treatment is only supportive and focuses on treatment of life-threatening complications.
Alright, time for a quick recap. Patau syndrome, or trisomy 13, is the least common and most severe trisomy in live births.
It is a chromosomal disorder where a person inherits three copies of chromosome 13, usually as a result of meiotic nondisjunction.
Characteristic findings include severe intellectual disability, microcephaly, holoprosencephaly, polydactyly, and cutis aplasia.
More severe defects include nose abnormalities and cyclopia. The affected babies usually die before birth.