Basic characteristics of the clinical phenotype

Rasopathies are a genetically heterogeneous group of pediatric diseases with overlapping genotype and phenotype (clinical presentation). They are due to mutations in genes involved in the RAS-MAPK signaling pathway. Most of the Rasopathies are characterized by specific facial characteristics, congenital heart diseases, skin anomalies, eye anomalies, hypotonia, hyperextensibility of the joints, developmental delay and are at increased risk of developing malignant diseases.

Rasopathies are among the most common autosomal dominant disorders affecting approximately 1 in 1,000 individuals.

Noonan syndrome is one of the most common diseases from the group of Rasopathies. This disease is characterized by blood clotting problems, heart defects, pulmonary valve stenosis, short stature and unusual facial features. People with Noonan syndrome may also have developmental delays, hearing loss, and vision problems or lymphedema.

Rasopathies include the following diseases:
· cardio-facio-cutaneous (CFC) syndrome
· LEOPARD syndrome
· Costello syndrome
· Neurofibromatosis type I
· Legius syndrome
· Baraitser-Winter syndrome
· Capillary malformation-arteriovenous malformation
· Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and genitopatellar syndrome (GPS)

The genes included in the panel were selected based on available evidence in databases and scientific literature for their role in the development of Rasopathies and Rasopathies-like diseases. Using the clinical phenotype, observed clinical symptoms are often insufficient to make a diagnosis due to the extreme phenotypic and genotypic heterogeneity of the Rasopathies. For this reason, the study of a panel of genes would help to make and/or confirm the clinical diagnosis.

Indications  for referral:
Ø Presence of relatives with Rasopathy
Ø Children born with multiple congenital malformations and dysmorphic features
Ø Children with short stature and/or developmental delay
Ø depicted clinical diagnosis Rasopathy obtained from the group of Rasopathies
Ø Presence of at least two of the following clinical symptoms: feeding problems, macrocephaly, short stature, developmental delay
Ø Presence of at least one of the following symptoms: cardiomyopathy, congenital heart indicated, arrhythmia, oncologically proven (bladder cancer, leukemia, rhabdomyosarcoma, pheochromocytoma), skin abnormalities (hyperkeratosis, cafe-au-lait spots, ulerythema oophorogenes, keratosis pilaris, excess palmar skin)

The benefits of carrying out a genetic analysis for carrying mutations in genes related to the development of Rasopathies are establishing and/or confirming a diagnosis, determining the risk of developing additional symptoms, supporting an individual approach to follow-up, therapy and symptom relief, providing information to family members about their risk of developing the disease, supports family planning and determines the risk of developing the disease in offspring.

Method: Next-generation sequencing (NovaSeq6000, Illumina).
The method involves bi-directional DNA sequencing of all coding exons and intron-exon boundaries of the target genes. The laboratory offers Sanger sequencing of a single exon or a pair of exons in the patient's relatives to determine carrier status in cases where the mutation is known (Test #182).
Sensitivity of the method: depends on the content of GC and AT, as well as the presence of segmentally duplicated genes.

What does the test involve?
· DNA isolation and sample storage.
· Next generation sequencing.
· Bioinformatic analysis of sequencing data. For each patient, only data for the gene(s) of interest were analyzed.
· Forming a written result of the genetic test.
· Diagnostic interpretation of results and genetic counseling.

Biological material: Venous blood or DNA
For more information, please read the "Biological material requirements and shipping information" carefully.