PATAU SYNDROME: SYMPTOMS, CAUSES, TREATMENT - NEUROPSYCHOLOGY - 2024

The Patau syndrome is a congenital genetic disease, due to the presence of a trisomy on chromosome 13. In particular, is the most common autosomal trisomy third after Down syndrome and Edwards Syndrome.

At the clinical level, this pathology affects multiple systems. Thus, various alterations and abnormalities in the nervous system, generalized growth retardation, cardiac, renal and musculoskeletal malformations usually appear.

The diagnosis is usually made during pregnancy in most cases, since clinical findings can be detected on routine ultrasound. However, to rule out false positives and misdiagnoses, various genetic tests are often performed to identify trisomy 13.

Regarding treatment, there is currently no cure for Patau syndrome, the survival of those affected does not usually exceed one year of life. The most common causes of death are cardiorespiratory complications.

Patau syndrome characteristics

Patau syndrome, also known as trisomy 13, is a medical condition of genetic origin that is associated with severe intellectual disability in addition to multiple physical disorders.

Affected people usually present serious heart abnormalities, various alterations in the nervous system, musculoskeletal malformations, facial alterations, muscular hypotonia, among others.

Due fundamentally to the serious multisystem affectation, people affected by Patau syndrome usually have a very reduced life expectancy.

This syndrome was initially identified in 1960 as a cytogenetic syndrome, that is, a genetic disorder associated with a chromosomal abnormality.

Chromosomes make up the genetic material of the cells that make up our body. Specifically, chromosomes are made up of deoxyribonucleic acid, also known by its acronym DNA, and it also has a composition characterized by the presence of different protein substances.

These chromosomes are usually structurally organized in pairs. In the case of human beings, we present 23 pairs of chromosomes, having a total of 46 of these.

In the case of Patau syndrome, the genetic abnormality specifically affects chromosome 13. Affected people have a trisomy of chromosome 13, that is, they have three copies of it.

At a more specific level, each egg and each sperm contains 23 chromosomes each, with the genetic material of the maternal and paternal parent. At the time of fertilization, the union of both cells results in the creation of 23 chromosomal pairs, or what is the same, the presence of 46 chromosomes in total.

However, there are times when an error or an altered event during the union, gives rise to the presence of genetic abnormalities, such as the presence of an extra chromosome in one of the couples.

In this way, this altered process will cause a series of neurobiological events during fetal development, which will alter the normal or expected genetic expression, giving rise to the presence of an organic involvement in various systems.

Statistics

Patau syndrome or trisomy 13 is considered a rare or rare disease. Different investigations estimate that this pathology presents an approximate frequency of 1 case per 5,000-12,000 newborns.

Despite this, in many cases the gestation of those affected by Patau syndrome does not usually reach term, so the frequency can increase significantly.

Thus, it has been observed that the annual rate of spontaneous abortions in this pathology is high, representing approximately 1% of the total of these.

Regarding the distribution of Patau syndrome by sex, it has been observed that this pathology affects women more frequently than men.

Characteristic signs and symptoms

At the clinical level, Patau syndrome can affect the body in a very heterogeneous way and between the different cases, so it is difficult to establish which are the cardinal signs and symptoms of this pathology.

However, different clinical reports such as that of Ribate molina, Puisac Uriel and Ramos Fuentes, highlight that the most frequent clinical findings are in those affected by Patau syndrome or trisomy 13:

Growth disturbance

The presence of a generalized growth retardation is one of the most frequent clinical findings. Specifically, slow or delayed growth can be observed in the prenatal and postnatal stages in approximately 87% of cases of Patau syndrome.

Alterations and malformations in the central nervous system (CNS)

In the case of the nervous system, the clinical findings that can be observed are diverse: hypotonia / hypertonia, apnea crisis, holoprosencephaly, microcephaly, psychomotor retardation or severe intellectual disability.

• Hypotonia / Muscle hypertonia: the term hypotonia refers to the presence of muscle flaccidity or reduced muscle tone, on the other hand, the term hypertonia refers to the presence of abnormally high muscle tone. Both medical events occur in 26-48% of affected individuals.
• Apnea crisis or episodes: Apnea episodes usually occur in about 48% of cases and consist of a reduction or paralysis of the breathing process for a short period of time.
• Holoprosencephaly: this term refers to the presence of different malformations at the brain level, mainly affecting the most anterior portion. This clinical finding can be seen in approximately 70% of cases of Patau syndrome.
• Microcephaly: around 86% of those affected have a lower head circumference than expected for their sex and maturational level.
• Psychomotor retardation: as a consequence of the various physical malformations, individuals with Patau syndrome will present serious difficulties to coordinate and execute all kinds of motor acts. This finding can be observed in 100% of the cases.
• Severe intellectual disability: cognitive impairment and severe intellectual disability is a clinical finding present in all diagnosed cases of Patau syndrome. Both neurological conditions develop as a result of extensive involvement of the nervous system.

Craniofacial alterations and malformations

At the facial and cranial level, there are also several clinical signs and symptoms that can be observed:

• Flattened forehead: abnormal development of the front of the skull is a sign present in all cases of Patau syndrome.
• Eye disorders: in the case of anomalies and pathologies that affect the eyes, these are present in approximately 88% of cases, the most frequent being microphthalmin, coloboma of the iris or ocular hypotelorism.
• Various malformations in the pinna: the progression of facial and cranial abnormalities can also affect the pinna in 80% of cases.
• Cleft lip and cleft palate: both oral malformations are present in approximately 56% of affected individuals. The term cleft refers to the presence of an incomplete closure of the lips, showing a fissure in the medial area, while the term cleft palate refers to an incomplete closure of the entire structure that makes up the palate or roof of the mouth .

Musculoskeletal malformations

Musculoskeletal abnormalities and malformations can affect various areas, the most common being the neck and extremities.

• Neck: the abnormalities that affect this specific area are present in most of the cases, specifically a short or poorly developed neck can be observed in 79% of those affected, while excess skin on the nape is present in 59 % of the cases.
• Extremities: the alterations that affect the extremities are diverse, it is possible to observe polydactyly in 76% of those affected, flexed or overlapping fingers in 68%, grooves in the hands in 64%, or hyperconvex nails in 68% of the affected.

Cardiovascular system disorders

Anomalies related to the cardiovascular system constitute the most serious medical condition in Patau syndrome, since it seriously threatens the survival of those affected.

In this case, the most frequent findings are intraventricular communication in 91%, persistent ductus arteriosus in 82%, and interventricular communication in 73%.

Genitourinary system disorders

The manifestations of the genitourinary system are usually related to the presence of cryptorchidism in men, polycystic kidney, bicornuate uterus in women, and hydronephrosis.

Causes

As we have pointed out previously, Patau syndrome is associated with the presence of genetic abnormalities on chromosome 13.

Most of the cases are due to the presence of three complete copies of chromosome 13, so the extra genetic material alters the normal development and, therefore, giving rise to the characteristic clinical course of Patau syndrome.

However, there are also cases of Patau syndrome due to duplications of parts of chromosome 13. It is possible that some affected people have all intact copies of this and an extra one attached to a different chromosome.

In addition, cases have also been reported in which individuals only present this type of genetic alteration in some cells of the body. In this case, the pathology acquires the name of mosaic trisomy 13, and therefore the presentation of signs and symptoms will depend on the type and number of cells affected.

Diagnosis

People affected with Patau syndrome present a set of clinical manifestations that are present from the moment of birth.

Based on the observation of the signs and symptoms, a clinical diagnosis is possible. However, when there is suspicion, it is essential to carry out other types of complementary tests to confirm the presence of Patau syndrome.

In these cases, the tests of choice are genetic karyotype tests, these are capable of giving us information about the presence / absence of an extra copy of chromosome 13.

In other cases, it is also possible to make the diagnosis in the prenatal stage, the performance of routine ultrasounds can show alarm indicators, for which, in general, genetic analyzes are requested to confirm their presence.

The most common tests in the prenatal stage are fetal ultrasound, amniocentesis, and chorionic villus sampling.

In addition, once the definitive diagnosis of Patau syndrome has been made, whether in the prenatal or postnatal phase, it is essential to carry out continuous medical monitoring to detect early possible medical complications that put the survival of the affected person at risk..

Treatment

At present, there is no specific or curative treatment for Patau syndrome, therefore, therapeutic interventions will be oriented towards the treatment of medical complications.

Due to the serious multisystemic involvement, people affected by Patau syndrome will require medical assistance from the moment of birth.

On the other hand, cardiac and respiratory disorders are the main causes of death, therefore, it is essential to carry out a detailed medical monitoring and treatment of both conditions.

In addition to pharmacological intervention for different signs and symptoms, it is also possible to use surgical procedures to correct some malformations and musculoskeletal abnormalities.

In summary, the treatment of Patau syndrome or trisomy 13 will be specific depending on each case and the associated clinical course. Generally, the intervention usually requires the coordinated work of different specialists: pediatricians, cardiologists, neurologists, etc.

References

1. Best, R. (2015). Patau Syndrome. Obtained from Medscape.
2. Genetics Home Reference. (2016). Trisomy 13. Obtained from Genetics Home Reference.
3. NIH. (2016). Trisomy 13. Retrieved from MedlinePlus.
4. NORD. (2007). Trisomy 13. Obtained from National Organization for Rare Disorders.
5. Orphanet. (2008). Trisomy 13. Obtained from Orphanet.
6. Ramos Fuentes, F. (2016). Patau syndrome (Trisomy 13). Obtained from Trisomy 18.
7. Ribate Molina, M., Puisac Uriel, B., & Ramos Fuentes, F. (2010). Trisomy 13 (Patau syndrome). Spanish Association of Pediatrics, 91-95.
8. Stanford Children's Health. (2016). Trisomy 18 and 13. Obtained from Stanford Children's Health.