EDWARDS SYNDROME: CHARACTERISTICS, SYMPTOMS, CAUSES - NEUROPSYCHOLOGY - 2025

The Edwards syndrome or trisomy 18 is a genetic disorder characterized by the presence of multiple congenital anomalies. It is the second most common autosomal chromosomal abnormality after trisomy 21 or Down syndrome.

Edwards syndrome has a polymorphic character; More than 130 different clinical manifestations have been described. Thus, associated pathologies can include: generalized pre and postnatal growth retardation, psychomotor retardation, cognitive deficit, craniofacial anomalies and malformations, musculoskeletal abnormalities in the extremities, muscle tone alterations, urogenital, gastrointestinal, neurological malformations and, in addition, cardiac alterations.

This syndrome is characterized by limited survival, usually not exceeding 15 days. The diagnosis is usually made during pregnancy, specialists can detect various abnormalities that alert to the possible presence of a medical pathology (ultrasonic physical examination, amniocentesis, etc.).

In the case of treatment, there is currently no cure for Edwards syndrome. Furthermore, the limited life expectancy of those affected makes it difficult to use palliative treatments.

Edwards syndrome characteristics

Edwards syndrome or trisomy (T18) is one of the first chromosomal abnormalities that have been described. Specifically, it was Edwards et al. Who, in 1960, reported the first case in a clinical report.

Currently, Edwards syndrome is considered the second most common autosomal chromosomal abnormality, after Down syndrome or trisomy 21.

Chromosomes are a component of the nucleus of cells. They are made up of deoxyribonucleic acid or DNA and different proteins and, therefore, contain a good part of the genetic information. Also, chromosomes are structured in pairs. In our case, we have 23 pairs, that is, 46 chromosomes in total.

In the case of Edwards syndrome, in the postnatal stage, during the process of cell division, an error occurs that results in the existence of an extra chromosome in pair 18, a triplet.

Thus, this genetic alteration will cause a cascade of abnormal events during fetal development, resulting in the presence of multisystem involvement.

Different case studies have shown that only 50% of affected babies who achieve a full-term pregnancy will be born alive.

Edwards syndrome presents a mortality of 95% in the first year of life. The remaining percentage (5%), usually live more than one year, of which 2% reach 5 years of life.

Statistics

After Down syndrome (T21), Edwards syndrome is the most common autosomal trisomy worldwide. It has an approximate prevalence of 1 case for every 3,600-8,500 live births.

However, the actual incidence varies if all prenatal diagnoses, intrauterine deaths, and voluntary terminations of pregnancy are considered. Therefore, the prevalence of Edwards syndrome could be as high as one case for every 2,500-2,600 pregnancies.

In the case of sex, it is more prevalent in women than in men.

Signs and symptoms

At the clinical level, Edwards syndrome is characterized by a broad medical picture, with more than 130 different alterations described.

Some authors, such as Pérez Aytés, describe the most frequent clinical manifestations, present in more than 50% of cases:

• Delayed development and growth in the prenatal and postnatal stages. Generally, the average weight at birth does not usually exceed 2300g.
• Presence of reduced muscle mass at birth.
• Hypotonia (reduced muscle tone) that tends to lead to hypertonia (elevated muscle tone)
• Craniofacial alterations and malformations: microcephaly (cranial and brain size below the corresponding value for the age and sex of the individual), prominence at the back of the head, dysplastic ears (absence or malformation of structures that make up the ear), micrognathia (abnormally small jaw).
• Alterations and malformations in the extremities: trisomic hand (presence of closed fists with significant difficulty in opening them), hypoplastic fingernails and toes (decreased thickness and texture), among others.
• Renurological alterations and malformations: presence of a horseshoe kidney (adoption of a U-shape).
• Cardiovascular disorders and malformations: congenital heart disease (prenatal heart disease).
• Gastrointestinal alterations and malformations: Meckel's diverticulum (tissue remaining from embryonic development due to poor closure of the bowel-umbilical cord junction), ectopic pancreas (presence of pancreatic tissue outside its usual location).
• Radiological signs: reduction of ossification nuclei, short sternum, among others.

In addition to these alterations, there are other affected systems such as the urogenital system, thorax-abdomen, skin, or central nervous system, however, they usually occur in less than half of the cases.

Medical complications

Between 90 and 95% of those affected die during the first year of life.

Median survival is between 2.5-70 days. Therefore, cases that reach the adolescent stage are rare and exceptional.

Thus, the main causes of death are congenital heart disease, apneas and pneumonia. In addition, among those who exceed the first years of life, other types of medical complications also occur:

• Feeding problems
• Scoliosis.
• Constipation.
• Recurrent infections (otitis, pneumonia, etc.).
• Significant psychomotor retardation.

Causes

Edwards syndrome is the product of a genetic alteration, specifically, it occurs on the number of chromosomes belonging to the 18 pair.

In most cases, trisomy 18 moves to every cell of the body, therefore, this additional genetic material alters the normal course of development and thus, gives rise to the characteristic clinical picture of this pathology.

However, in a small percentage of cases (5%), the extra copy of chromosome 18 is only present in some cells, giving a mosaic trisomy.

Partial trisomy and mosaicism usually present an incomplete clinical phenomenon. Therefore, the severity of this pathology will depend fundamentally on the number and type of cells affected.

Risk factor's

Despite the fact that Edwards syndrome occurs in isolation in families without a history, some factors have been identified that increase its probability of occurrence:

• The risk of recurrence in families with other cases is 0.55%.
• More likely when the mother is older during pregnancy, after 35 years of age the frequency increases progressively.

Diagnosis

In most cases, the presence of Edwards syndrome is suspected during the prenatal stage.

In general, the presence of ultrasound markers, anatomical abnormalities or biochemical tests in the maternal serum usually offer reliable indicators of their presence.

Regardless of the time of the examination, a DNA sample is extracted to confirm the diagnosis, and a karyotype (image of the chromosomal configuration) is performed to confirm alterations in the 18 pair.

Treatment

There is currently no curative treatment for Edwards syndrome. Furthermore, poor survival makes it difficult to design specific therapeutic interventions.

Although the factors that contribute to the prolonged survival of individuals with Edwards syndrome are not exactly known, all medical interventions are aimed at alleviating secondary medical complications.

In this way, the most beneficial thing is to use a comprehensive rehabilitation treatment consisting of physical, cognitive, and occupational therapy, among others.

References

1. Bustillos-Villalta, K., & Quiñones-Campos, M. (2014). Long Survival Edwards Syndrome: Effect of Comprehensive Rehabilitation Treatment. Rev Med Hered., 89-92.
2. Denardin, D., Savaris, F., Campos da Cunha, A., da Silveira Betat, R., Bianchi Telles, J., Vieira Targa, L.,… Machado Rosa, R. (2015). Retrospective cohort of trisomy 18 (Edwards syndrome). Sao Paulo Med, 20-25.
3. Fabiano, R., Cardoso, R., Boff, M., Zen, P., Graziadio, C., & Adriano Paskulin, G. (2013). Craniofacial abnormalities among patients with Edwards Syndrome. Rev Paul Pediatr, 293-298.
4. NIH. (2016). trisomy 18. Obtained from Genetics Home Reference.
5. NIH. (2016). Trisomy 18. Retrieved from MedlinePlus.
6. Pérez Aytés, A. (2000). Edwards syndrome (Trisomy 18). Spanish Association of Pediatrics, editors. Diagnostic and Therapeutic Protocols, 19-22.
7. Simón-Bautista, D., Melián-Suárez, A., Santana-Casiano, I., Martín-Del Rosario, F., & de la Peña-Naranjo, E. (2008). Rehabilitative treatment of the patient with long-survival Edwards syndrome. An Pediatr (Barc), 301-315.
8. Trisomy 18 Foundation. (2016). WHAT IS TRISOMY 18? Obtained from Trisomy 18 Foundation.