PrenatalSafe Complete Plus

PrenatalSAFE Complete Plus screens for the following:

• DiGeorge Syndrome deletion 22q11.2
• Cri-du-chat Syndrome deletion 5p15.3
• Prader-Willi Syndrome deletion 15q11.2
• Angelman Syndrome deletion 15q11.2
• 1p36 Deletion Syndrome deletion 1p36
• Wolf-Hirschhorn Syndrome deletion 4p16.3
• Jacobsen Syndrome deletion 11q23
• Langer-Giedion Syndrome deletion 8q24.11-q24.13
• Smith-Magenis Syndrome deletion 17p11.2

What are Microdeletions?

Microdeletion syndromes are genetic disorders that occur when a small piece of genetic material is missing from a person’s DNA. This genetic abnormality, known as a microdeletion, can impact one or more genes, leading to various physical and developmental issues.

For example, Prader-Willi syndrome affects cognitive development, causing intellectual disability, behavioural problems, feeding issues, and weak muscle tone. Another example is DiGeorge syndrome, which impacts the immune system, potentially causing heart defects, cleft palate, and developmental delays. Similarly, Cri du Chat syndrome affects physical and cognitive development, resulting in distinctive facial features and intellectual disability.

These microdeletion syndromes can be diagnosed through genetic testing, identified prenatally or in early childhood. Treatment options depend on the specific symptoms and may include speech and occupational therapy, medications, and surgeries to manage associated medical conditions. Early diagnosis and intervention are crucial for managing these conditions effectively.

PrenatalSAFE Complete Plus screens for the following:

• CFTR Cystic Fibrosis
• CX26 (GJB2) Deafness Autosomal Recessive Type 1A
• CX30 (GJB6) Deafness Autosomal Recessive Type 1B
• HBB Beta Thalassemia
• HBB Sickle Cell Anemia

What are inherited Genetic Diseases?

Inherited genetic diseases are conditions caused by abnormalities in an individual’s DNA, passed down from parents to their offspring. These genetic abnormalities can include mutations in a single gene, multiple genes, or changes in chromosome structure or number. Here are key points to understand about inherited genetic diseases:

• Single-Gene Disorders
• Multifactorial Disorders.
• Chromosomal Disorders.
• Mitochondrial Disorders.

Inherited genetic diseases can have a wide range of effects, from mild to severe, and can impact various aspects of an individual’s health and development. Early diagnosis and genetic counselling are crucial for managing these conditions and providing the best possible care and support for affected individuals and their families.

PrenatalSAFE Complete Plus screens for the following:

• Alagille Syndrome JAG1
• CHARGE Syndrome CHD7
• Cornelia de Lange Syndrome, type 5 HDAC8
• Cornelia de Lange Syndrome, type 1 NIPBL
• Rett Syndrome MECP2
• Sotos Syndrome, type 1 NSD1
• Bohring-Opitz Syndrome ASXL1
• Schinzel-Giedion Syndrome SETBP1
• Holoprosencephaly SIX3

• Noonan Syndrome, type 1 (LEOPARD Syndrome 1 PTPN11)
• Noonan Syndrome, type 3 KRAS
• Noonan Syndrome, type 4 SOS1
• Noonan Syndrome, type 5 (LEOPARD Syndrome 2 RAF1)
• Noonan Syndrome, type 6 NRAS
• Noonan Syndrome, type 8 RIT1
• Noonan Syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) CBL
• Noonan syndrome-like disorder with loose anagen hair SHOC2
• Cardiofaciocutaneous Syndrome, type 1 BRAF
• Cardiofaciocutaneous Syndrome 3 MAP2K1
• Cardiofaciocutaneous Syndrome 4 MAP2K2

• Achondrogenesis, type II COL2A1
• Achondroplasia FGFR3
• CATSHL Syndrome
• Crouzon syndrome with acanthosis nigricans
• Ehlers-Danlos Syndrome cardiac valvular form
• Ehlers-Danlos syndrome, classic
• Ehlers-Danlos syndrome, type VIIA
• Ehlers-Danlos, type VIIB Syndrome
• Hypochondroplasia
• Muenke syndrome
• Osteogenesis imperfecta, type I
• Osteogenesis imperfecta, type II
• Osteogenesis imperfecta, type III
• Osteogenesis imperfecta, type IV
• Thanatophoric dysplasia, type I
• Thanatophoric dysplasia, type II

• Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis FGFR2
• Apert Syndrome
• Crouzon Syndrome
• Jackson-Weiss Syndrome
• Pfeiffer Syndrome, type 1
• Pfeiffer Syndrome, type 2
• Pfeiffer Syndrome, type 3

What are De Novo Genetic Diseases?

De Novo diseases are genetic disorders caused by spontaneous mutations not inherited from either parent. These genetic changes occur spontaneously during conception, either in the egg or sperm or shortly after fertilisation.

De Novo diseases can affect any part of the body, leading to a wide range of symptoms depending on the specific genetic abnormality. Because these conditions are not inherited, they can appear in families with no history of the condition. This spontaneous occurrence makes early detection crucial for effective management and care.

 No, it’s not. Instead, it represents a clever approach that combines cutting-edge ultrasound technology and expertise with the most advanced NIPT available. This unique approach ensures the broadest coverage of conditions screened during pregnancy.

No, the SMART Ttest® is not a diagnostic test. It is a screening test that provides valuable information about the probability or likelihood of certain genetic conditions in the developing fetus. If the PrenatalSafe Complete Plus indicates a positive finding or an increased risk of a genetic condition, further diagnostic tests may be recommended to confirm the diagnosis.

Diagnostic tests, such as chorionic villus sampling (CVS) or amniocentesis, are invasive procedures that directly examine the fetal genetic material and provide a definitive diagnosis of genetic conditions. These tests carry a small risk of miscarriage and are typically offered when there is a significant concern or when screening tests like the SMART TEST suggest a potential issue.

In summary, the SMART Test® Genoma is a non-invasive screening tool that helps assess the risk of certain genetic conditions during pregnancy. It is an important step in identifying pregnancies at higher risk, but a confirmed diagnosis is typically obtained through diagnostic tests if necessary.

The PrenatalSafe Complete Plus NIPT can not be used in pregnancies with:

• triplets
• a history of or active malignancy
• a pregnancy with fetal demise 
• a history of bone marrow or organ transplants
• mosaicism for the parents
• maternal aneuploidy (chromosomal abnormality)
• in women under the age of 18

Please note that singleton IVF pregnancies are eligible for SMART TEST NIPT.

The turnaround time for the PrenatalSafe Complete Plus test, from the moment of sample collection to receiving results, typically spans 15-20 working days. Please note that this timeframe includes the time required for both sample collection and transfer to the Eurofins Genoma laboratory in Rome, Italy, where the analysis is conducted.

Following your initial scan appointment, you will receive a comprehensive scan report from Dr. Fred Ushakov. It is available in hard copy and PDF format and securely delivered via our cloud system, Tricefy.

We will provide you with two sets of PrenatalSafe Complete Plus NIPT results: one for chromosomal conditions (the first set) and another for single-gene disorders (the second set). Once we receive these NIPT test results from the laboratory, our clinician carefully reviews and approves them. Subsequently, one of our friendly clinical staff members will contact you by phone to explain and interpret the results. We will also send you a digital copy of the test results through Tricefy.

Our medical team will promptly contact you if your PrenatalSafe Complete Plus result indicates a high likelihood of a rare genetic disease. Our clinician will provide a detailed explanation of the recommended next steps.

We will facilitate a referral to our Genetic Counselor for comprehensive counselling and potential further referral for diagnostic tests such as chorionic villus sampling (CVS) or amniocentesis.

We understand the importance of support during this process. To assist you, our clinic will cover the cost of the initial private genetic counselling session. However, please be aware that our clinic does not cover follow-up genetic consultations or the expenses associated with invasive diagnostic procedures and genetic tests.

Simultaneously, we will arrange an expert fetal scan conducted by Dr. Fred Ushakov as swiftly as possible. This specialized scan aims to provide a targeted examination of the fetus, focusing on identifying any structural findings that may be associated with the specific genetic condition under consideration.

The PrenatalSafe Complete Plus NIPT platform is known for its enhanced accuracy. To further enhance precision, this platform can benefit from a small sample of the father’s DNA collected through a painless cheek swab known as a mouth or buccal swab. While this step is optional, we highly recommend it.

Modern DNA analysis techniques have evolved to be faster and more precise, enabling the use of even tiny DNA samples for analysis. This advancement ensures that the testing process is efficient and delivers reliable results.

PrenatalSafe Complete Plus, which is an extended NIPT panel included in SMART Test® Genoma, provides valuable information about your baby’s health during pregnancy. However, it’s important to understand that, like any screening test, it has limitations. 

False Positives: Sometimes, the test may indicate a positive result for a specific condition when the baby doesn’t actually have that condition. This can happen due to various factors, including biological variability and limitations in the screening process. It’s essential to remember that a positive result from PrenatalSafe Complete Plus is not a definitive diagnosis.

False Negatives: On the other hand, there’s a possibility that the test may yield a negative result even if the baby does have a particular condition. This can occur if the baby’s genetic material in the mother’s bloodstream is not representative of the entire fetal genetic makeup or if the condition is caused by a rare mutation not covered by the test. A negative result doesn’t guarantee the baby is free from all conditions checked.

Inconclusive Results: In some cases, the test may not provide a clear result due to technical reasons or insufficient fetal DNA in the maternal blood sample. This is known as an inconclusive result. It means the test couldn’t definitively determine the status of certain conditions.

It’s crucial to understand that PrenatalSafe Complete Plus is a screening test designed to assess the likelihood of specific genetic conditions in your baby. If the test indicates a positive result or if you have concerns about the limitations mentioned above, further diagnostic tests such as chorionic villus sampling (CVS) or amniocentesis may be recommended to confirm or rule out specific conditions. These diagnostic tests provide more definitive information but come with a small risk of miscarriage.

You can discuss any questions or concerns with us before the test to ensure the best care for you and your baby.

Pros and Cons of  SMART Test® Genoma and SMART Test® KNOVA

SMART Test® Genoma:

Pros:

1. Extensive Chromosomal Screening: Covers all chromosomes for rare trisomies and checks for deletions and duplications over 7Mb.
2. Inherited Disease Screening: Screens for 5 inherited genetic diseases.
3. Twin Pregnancy Compatibility: Suitable for twin pregnancies and vanishing twin scenarios.
4. Donor Egg Compatibility: Suitable for pregnancies with donor eggs.

Cons:

1. Higher Cost: Priced at £1490, more expensive than the KNOVA version.
2. Longer Turnaround: Second genetic report takes up to 20-22 working days.
3. Additional Step: Requires a paternal mouth swab, adding complexity.

SMART Test® KNOVA:

Pros:

1. Affordable: Priced at £990, it’s cheaper than the Genoma version.
2. Quick Results: Receive a comprehensive report within 7-14 working days.
3. Advanced Screening: Includes 12 microdeletions and 56 de novo genetic diseases.
4. Targeted Chromosomal Screening: This screening method screens only for clinically important trisomies T15, T16, and T22, reducing false positives.
5. High NT Screening: Excellent for non-invasive screening of fetuses with high NT.

Cons:

1. No Inherited Disease Screening: Does not screen for inherited genetic diseases. Add-on UNITY carrier screening is available for £650.
2. Not for Twins: Unsuitable for twin pregnancies or vanishing twin scenarios.
3. Not for Donor Eggs: Inapplicable for donor egg pregnancies.

Summary

Both tests effectively screen for trisomy 21 (Down syndrome). The SMART Test® KNOVA is ideal for those seeking cost-effective and quick NIPT focused on de novo genetic diseases and microdeletions. It’s not suitable for twin pregnancies or donor egg pregnancies.

The SMART Test® Genoma offers detailed chromosomal analysis, suitable for twin pregnancies and donor egg scenarios, but it is more expensive and takes longer to complete.

London Pregnancy Clinic offers both options to meet diverse needs and ensure the most advanced prenatal screening in the UK.

Note: Test costs reflect lab labour and technology, not diagnostic value. Newer tests may be cheaper due to marketing strategies and testing volume.

When considering genetic screening options during pregnancy, it’s essential to understand the differences between tests like SMART Test® and Panorama, especially when it comes to screening for microdeletions.

SMART Test®:

SMART Test® Genoma uses PrenatalSafe Complete Plus NIPT: an extensive genetic screening panel that covers approximately 100 rare genetic diseases, including a comprehensive set of microdeletions. Microdeletions are specific genetic conditions where a small portion of a chromosome is missing.

SMART Test® provides comprehensive coverage, including all microdeletions checked by Panorama and many more. This means it not only screens for 22q deletion (DiGeorge syndrome) but also checks for other microdeletions and genetic variations that may be associated with rare diseases.

By choosing SMART Test®, you’re opting for a broader and more comprehensive genetic screening, which can provide insights into a wide range of genetic conditions and syndromes. It offers a more extensive look into your baby’s genetic health.

Panorama Microdeletions Screening:

Panorama is a prenatal screening test that includes screening for a specific set of microdeletions, including 22q deletion (DiGeorge syndrome), as part of its package. It screens for five specific microdeletions.

While Panorama provides valuable information about these selected microdeletions, it has a more focused scope compared to SMART Test®. It does not offer the same breadth of coverage for rare genetic diseases beyond the included microdeletions.

In summary, SMART Test® options offer a much more extended genetic screening, encompassing a comprehensive range of microdeletions and rare genetic diseases, including those checked by Panorama. By choosing SMART Test®, you opt for a broader and more inclusive screening that can provide a more extensive view of your baby’s genetic health.

SMART Test® Genoma utilises PrenatalSafe Complete Plus an extensive genetic screening panel that checks for approximately 100 chromosomal and genetic conditions. It provides comprehensive coverage across a wide range of genetic disorders and syndromes.

In contrast, UNITY Complete screens for a more limited set of conditions, covering approximately 12 different conditions, including 5 Inherited Genetic Diseases. While UNITY Complete provides valuable genetic insights, it is not as extensive in its coverage as SMART Test® Genoma.

However, UNITY Complete includes screening for two additional genetic syndromes: spinal muscular atrophy (SMA) and alpha-thalassemia.
UNITY Complete can also determine the fetal Rh blood group for Rh-negative mothers, providing valuable information about the baby’s Rh blood type.

PrenatalSafe complete plus (included in SMART Test®) screens for mutations associated with Noonan Syndrome:

Noonan syndrome is a genetic disorder characterized by various physical and developmental features. It can affect multiple systems of the body and is primarily caused by mutations in genes related to the Ras-MAPK pathway, with PTPN11 being one of the most commonly affected genes. Notably, Noonan syndrome often arises as a de novo mutation, even in healthy parents, and it is associated with a range of clinical features.

Incidence: The incidence of Noonan syndrome is estimated to be approximately 1 in 1,000 to 1 in 2,500 live births, making it one of the more common genetic syndromes. While it can occur in both males and females of all ethnic backgrounds, it may go undiagnosed or underdiagnosed due to the variability of its features and the fact that some individuals have mild or atypical symptoms.

Prenatal Screening: During prenatal screening, Noonan syndrome is often associated with increased nuchal translucency (NT), which is a measurement of the thickness of the fluid-filled space at the back of the baby’s neck. An increased NT measurement may raise suspicion of Noonan syndrome and prompt further genetic testing and evaluation.

Physical Features: Individuals with Noonan syndrome often exhibit characteristic facial features, such as widely spaced eyes, a short neck, low-set ears, and a webbed neck. These features can vary in their expression and may become less noticeable with age.

Heart Abnormalities: Many people with Noonan syndrome have congenital heart defects, which can range from mild to severe. These heart issues may require medical intervention or surgery.

Developmental Delays: Children with Noonan syndrome may experience developmental delays, including speech and motor skill delays. However, with appropriate therapies and support, many can achieve their developmental milestones.

Growth Issues: Growth may be affected, resulting in shorter stature than average. Growth hormone therapy may be considered to help increase height.

Other Health Concerns: Noonan syndrome can also impact various systems of the body, leading to potential issues with bleeding and clotting, skeletal abnormalities, vision and hearing problems, and an increased risk of certain cancers.

Treatment: Management of Noonan syndrome typically involves a multidisciplinary approach. Medical care may address heart issues, developmental delays, and other health concerns. Early intervention and therapies can help children with Noonan syndrome reach their full potential.

Prognosis: The outlook for individuals with Noonan syndrome varies depending on the severity of the condition and the presence of associated health issues. Many individuals with Noonan syndrome lead fulfilling lives with appropriate medical care and support.

Genetic Counselling: Families affected by Noonan syndrome may benefit from genetic counselling to understand the genetic basis of the condition, the risk of future pregnancies being affected, and the possibility of de novo mutations occurring.

Overall, Noonan syndrome is a relatively common genetic disorder with a wide range of clinical manifestations. Increased nuchal translucency during prenatal screening can be a strong indicator of the condition, leading to further evaluation and diagnosis. With early detection, appropriate medical care, and ongoing support, individuals with Noonan syndrome can lead healthy and fulfilling lives.

PrenatalSafe complete plus (included in SMART Test®) screens for mutations associated with achondroplasia:

Achondroplasia is a rare genetic disorder that primarily affects bone growth and development. It is characterized by short stature, disproportionate limbs, and various skeletal abnormalities. Achondroplasia is caused by a specific mutation in the FGFR3 gene and follows an autosomal dominant inheritance pattern. Notably, it often arises as a de novo mutation, meaning it occurs spontaneously in individuals with no family history of the condition.

Here are key points about achondroplasia:

Genetic Basis: Achondroplasia is primarily caused by a mutation in the FGFR3 gene, specifically the G380R mutation. This mutation leads to abnormal cartilage and bone development.

Incidence: Achondroplasia is a rare genetic disorder, with an estimated incidence of about 1 in 15,000 to 40,000 live births. It is one of the most common forms of short-limbed dwarfism.

Physical Features: Individuals with achondroplasia typically have short stature, with disproportionately short arms and legs compared to their trunk. They may also exhibit characteristic facial features, such as a prominent forehead, a flattened nasal bridge, and a small chin.

Skeletal Abnormalities: Achondroplasia can result in various skeletal abnormalities, including bowed legs, a curved spine (kyphosis and lordosis), and joint problems. These issues can lead to mobility challenges.

Health Concerns: People with achondroplasia may experience health complications, such as spinal stenosis (narrowing of the spinal canal), respiratory difficulties, and ear infections. Regular medical monitoring and management of these issues are essential.

Developmental Milestones: Children with achondroplasia often achieve developmental milestones on a typical schedule. Early intervention and physical therapy can be helpful in addressing mobility and orthopaedic concerns.

De Novo Mutations: Many individuals with achondroplasia have no family history of the condition. Instead, the condition often arises as a de novo mutation in the FGFR3 gene. In such cases, healthy parents can have a child with achondroplasia due to this spontaneous genetic change.

Prognosis: With proper medical care and support, individuals with achondroplasia can lead healthy and fulfilling lives. Early interventions, orthopaedic surgeries if necessary, and ongoing medical monitoring are important aspects of managing the condition.

Genetic Counselling: Families affected by achondroplasia may benefit from genetic counselling to understand the genetic basis of the condition, its de novo nature, and the potential risks associated with future pregnancies.

Achondroplasia is a complex genetic disorder with unique physical characteristics, but individuals with the condition can thrive with appropriate care and support. Early diagnosis, medical interventions when needed, and access to specialized medical care contribute to positive outcomes for those living with achondroplasia.