Newborn Genetic Screening

1. The test standardly includes SMN1 analysis, the causative gene for spinal muscular atarophy (SMA), which is one of the three most common autosomal recessive diseases in Bulgaria.

Bulgaria is among the European countries with the highest prevalence of SMN1-associated spinal muscular atrophy, which, if left untreated, in its most common form leads to death before the age of two years.

2. Each test result is accompanied by a written medical opinion prepared by specialists in Medical Genetics at  Nadezhda Hospital, providing information to help parents understand the result.

If the test result is positive, the report explains:

• the nature of the condition,

• available treatment options,

• where to seek follow-up care by a clinical specialist, and

• what steps should be taken prior to the specialist consultation.

3. Parents receive comprehensive care in one place at Nadezhda – delivery, testing, and genetic consultation.

4. The newborn genetic screening at Nadezhda Hospital includes a broad panel of carefully selected conditions, chosen by experienced specialists and tailored to the specific technological requirements for analyzing genes that are analytically challenging (DMD, CYP21A2, SMN1).

• CYP21A2 – Common pathogenic variants are detected using mini-sequencing. Additionally, 20–30% of clinical cases are caused by large deletions/duplications of this gene; therefore, detailed qPCR analysis is included.

• DMD – Only 20–35% of reported cases can be detected by NGS alone. Large deletions/duplications account for the remaining 65–80% of cases; therefore, MLPA analysis is included.

• SMN1 – The primary mutation causing SMA (~96% of cases) consists of large biallelic deletions in the SMN1 gene. qPCR testing is included to detect these variants.

5. The option for additional medical genetic consultation with Medical Genetics specialists from the Genetic Laboratory team at Nadezhda Hospital.

6. Parents have the right to choose whether they wish to be informed about carrier status.

IMPORTANT!
Being a healthy carrier does NOT mean having the disease. Every individual is a healthy carrier of several recessive mutations, which has no direct impact on their own health. Carrier status is associated with a potential risk for the carrier’s children to be affected by the respective condition.

Carrier status will be reported only if explicitly requested (by ticking the relevant option in the Informed Consent and Declaration).

There is no strict deadline, but it is recommended to perform the test within the first month of life.

The maximum benefit of screening is achieved when the sample is collected as early as possible, allowing treatment to begin promptly if needed. Ideally, sampling should occur by the 5th day after birth, simultaneously with the state-funded newborn screening test.

IMPORTANT!
Prematurity, feeding method, illness, or medication use are not contraindications for performing the test.

In the event of a positive result, clinical evaluation, confirmatory diagnostic testing, and initiation of treatment (if required) are necessary. This can prevent the onset of symptoms or reduce their severity, thereby improving the long-term prognosis.

A venous blood sample is collected in a test tube and sent to the Unilabs laboratory in Portugal.

The turnaround time for the results is 4–6 calendar weeks.

The cost of the test is 980.00 € / 1,916.71 BGN.

1. Positive result

• For dominant disorders: identification of a pathogenic or likely pathogenic variant in a gene causing a dominant disease.

• For recessive disorders: identification of at least two pathogenic or likely pathogenic variants in a gene causing a recessive disease.

For X-linked disorders, the clinical implications of carrying one or more pathogenic or likely pathogenic variants may differ between males and females.

2. Negative result
No pathogenic or likely pathogenic variants are identified in any of the analyzed genes. A negative result reduces but does not eliminate the possibility of one of the tested conditions. Detection is limited by current scientific knowledge and by the technical limitations of the test.

3. Carrier result
A pathogenic or likely pathogenic variant is identified in a gene associated with an autosomal recessive or X-linked recessive disorder (if the newborn is female). Typically, a pathogenic variant in the second allele would be required for disease manifestation. Carrier status is reported only upon explicit request.

4. Uninformative result
The result may be classified as uninformative if the sample fails quality control due to insufficient DNA concentration or quality—most commonly caused by inadequate sampling or sample degradation during handling, storage, or transport.

Approximately 3–5% of infants are born with a congenital anomaly, with causes that may be diverse. A child with a negative newborn genetic screening result may still be at risk of having or developing a genetic disorder. This test provides information only for the conditions included in the screening panel, and not all variants within these genes can be detected. Additional testing may be recommended by the treating clinician if necessary.

Genetic testing may yield results with clinical and reproductive implications for both the individual and their family members.

Screening programs aim to identify individuals within a population who are at high risk for developing specific diseases, with sufficient sensitivity and specificity. Screening programs are a core component of genetic disease prevention.

The goal of national neonatal screening programs is to detect affected newborns before symptom onset and initiate timely treatment, thereby preventing disease manifestation, improving disease control, and ensuring a better prognosis. The number of conditions included in national neonatal screening programs varies; within the European Union, newborns are screened for between 3 and more than 40 conditions.