Early detection of rare diseases can be done at early stages. The La Paz University Hospital is a reference in this field, integrating research, advanced diagnosis, and innovative treatments to improve maternal-fetal health.
"The center conducted its first genetic study in 1966 and, years later, obtained the first prenatal karyotype with amniocentesis. For a long time, this was the only test to diagnose chromosomal abnormalities, especially trisomy 21," recall Karen Heath and María Elena Mansilla, coordinator and sub-coordinator, respectively, of the Institute of Medical and Molecular Genetics (INGEMM) at the Madrid hospital center.
In the early 2000s, La Paz incorporated array-CGH technology to detect DNA copy number alterations with higher resolution and speed.
Recently, massive sequencing has improved diagnosis by analyzing multiple genes simultaneously.
"Today, all techniques are complementary and allow for numerous prenatal diagnoses," both experts point out. There are also studies of circulating free DNA in maternal plasma, which are a screening test for common chromosomal aneuploidies or alterations in the number of chromosomes.
Even today, the prenatal diagnosis of a disease requires an invasive technique (chorionic biopsy, amniocentesis, or cordocentesis), not without complications and which can interfere with gestation.
"When a fetal sample is available, genetic tests can be performed to attempt a diagnosis," they explain.
There are situations that encourage prenatal diagnosis, and reproductive medicine is key in this area, as more than 80% of cases have a genetic cause. "Techniques such as genetic matching allow knowing if two parents have a risk of affected offspring, avoiding the possibility of transmitting the studied genetic diseases," point out from the assisted reproduction clinic Ginemed.
However, many rare diseases lack prenatal manifestations during pregnancy, making detection difficult.
Discovering them early helps families make decisions based on their individual needs and values and understand the origin of the conditions and their possible recurrence in other pregnancies.
An early diagnosis also allows healthcare professionals to make decisions such as the delivery method, refer the baby to specialists for treatment at birth, or avoid the diagnostic odyssey after birth, as well as prescribe intrauterine treatments.
The benefits of prenatal testing outweigh its costs and should not be a barrier for healthcare systems. The most complex aspect of genetic tests is interpreting them, as they allow finding the cause, reaching a diagnosis, or making unexpected findings.
The most diagnosed diseases prenatally are still chromosomal abnormalities such as Down syndrome and Turner syndrome.
On the other hand, the most detected monogenic diseases are those that presentultrasound malformations, such as skeletal dysplasias, rasopathies, and ciliopathies, which constitute a heterogeneous group of genetic diseases (renal polycystic kidney disease or Joubert and Meckel syndromes), as well as other neuromuscular diseases.
The great challenge is to achieve an ideal prenatal diagnostic test: non-invasive, performed as early as possible in pregnancy, with low cost, providing a quick response and a significant result. Currently, no test is ideal, and often several must be combined to reach a diagnosis.
In any case, some recent studies have shown the feasibility of whole-genome sequencingfrom a single cell to detect genetic diseases prenatally.
Research shows that non-invasive prenatal tests based on one or two cells can identify genetic mutations responsible for diseases such as cystic fibrosis or thalassemia.
Another challenge is to better understand how rare diseases manifest prenatally and establish correlations between the fetal phenotype (its clinical characteristics) and the genotype (genetic alteration).
For now, new tools are emerging, such as those of doctors in the public Primary Care network of the Community of Madrid, who already have their own ChatGPT to help diagnose rare diseases. This is SermasGPT, a generative artificial intelligence tool developed in collaboration with Microsoft and the Foundation 29, inspired by the ChatGPT model, known for its ability to generate quick and accurate responses.