What is Fryns syndrome? 

Fryns syndrome is an extremely rare genetic condition that affects the body's development. Its prevalence is estimated at 1/14000 births, and in 4-10% of congenital diaphragmatic hernia (CDH) patients. How the disorder affects the body is variable amongst individuals, making the diagnosis of this condition difficult. Key characteristics include defects in the diaphragm, abnormalities in facial characteristics, and abnormal fingers and toes. Additionally, disruptions in the development of the cardiovascular system, gastrointestinal system, kidneys and reproductive organs.^1,2 

The disorder was initially discovered when observing that two stillborn siblings exhibited features presently associated with Fryns syndrome. Due to the babies being stillborn, Fryns was considered lethal. However, upon further research, it has been discovered that this is not the case. Figuring out the full history behind Fryns syndrome has proven to be difficult due to high mortality rates in infants.³

The role of a genetic counsellor

Genetic counsellors are healthcare professionals and play a vital role in the diagnostic process of rare genetic conditions, such as Fryns syndrome. They are crucial in assisting families to comprehend complex scientific information and help their understanding of the nature of genetic conditions. The roles of a genetic counsellor include collecting important information regarding patient family history and inheritance patterns to discover if they’re at risk of inheriting a genetic condition.

Then they provide insight on possible genetic tests and other procedures that could confirm or reject the presence of a genetic disorder, including the benefits and risks of each investigation. Once all the necessary tests are performed, it is the genetic counsellor’s responsibility to communicate the results. These sessions involve assisting families with any emotional reaction as a consequence of test results. In cases of a positive result, next steps involve discussing the treatment options available with the patient, as well as psychosocial counselling if suitable for their circumstances.⁴

Understanding Fryns syndrome

To be able to understand Fryns syndrome, it’s important to initially acknowledge the genetic basis of the disorder. The cause of Fryns syndrome has not yet been identified due to the lack of a specific genetic change that has been associated with all of the symptoms. However, there have been abnormalities identified, including duplications and deletions in multiple chromosomal regions. These mutations have previously been associated with CDH, and other features of Fryns syndrome.

On the other hand, it has been identified that the patterns of inheritance are autosomal recessive. This is where both copies of a gene in each cell contain mutations, yet the gene in question has not been identified. Parents with autosomal recessive conditions only carry one copy of the mutated gene, so they do not present symptoms of Fryns syndrome.³ 

It’s also important to consider the clinical manifestations of the syndrome. Fryns syndrome has a massive impact on facial characteristics, sometimes causing wide-set and small eyes, cornea clouding (the transparent layer in the eye that covers the iris and pupil). As well as an outer broad/flat nasal bridge with a thick nasal tip, wide space between the nose and upper lip, wide mouth, a hole in the roof of the mouth (cleft palate), small chin and low-set abnormal ears.

Additionally, it can cause underdeveloped fingers and toes, with small and or missing nails. Infants with Fryns syndrome are highly likely to have congenital diaphragmatic hernia (CDH), which is a structural defect in the diaphragm that develops in the womb – this “hole” can allow the stomach and intestines to move up into the chest, resulting in crowding of the heart and lungs, which disrupts the development of the lungs and is known as pulmonary hypoplasia. This may lead to breathing problems in the affected infants. Furthermore, this disorder can affect other organ systems, including structural brain and cardiac malformations, and abdominal defects, such as intestinal malrotations.³

Role of genetic counselling in Fryns syndrome

Due to the high mortality of Fryns syndrome, early detection is important. In the first trimester of pregnancy, the patient may be offered an ultrasound scan, which can identify features associated with Fryns syndrome, such as diaphragm hernias (cavities in the diaphragm). Prenatal ultrasound scans can be used to identify cleft lips and palates, cardiovascular defects, and renal malformations. Genetic counsellors will be able to discuss possible treatments for the hernia and other malformations during the pregnancy.

However, facial dysmorphisms are difficult to detect prenatally, so they remain undetected until postnatal examinations. Due to the nature of the syndrome, diagnosis isn’t definitive until postnatal tests and genetic investigation.⁵ As the fatality risk is high, the genetic counsellor is likely to discuss the option to terminate the pregnancy, should the family decide they do not wish to continue. If the family decides to continue with the pregnancy, the counsellor provides information on how the family can educate themselves on how to care for an infant with Fryns syndrome. 

Postnatal examinations can include both clinical and molecular diagnosis. The clinical diagnosis includes six criteria such as: identifying diaphragmatic defects, characteristic facial appearance, distal digital hypoplasia, pulmonary hypoplasia, a minimum of one associated anomaly, and family history consistent with autosomal recessive inheritance. The molecular diagnosis includes two types of genetic testing, gene-targeted testing (e.g. single-gene testing) and comprehensive genomic testing (e.g. genome sequencing). Depending on the phenotype, the type of test used will differ.

If the individual displays phenotypes (physical characteristics) as those listed in the clinical diagnosis, gene-targeted testing can be used. Whereas, if they display phenotypes that are general amongst many other genetic disorders, diagnosis will likely require comprehensive genomic testing. Once the diagnosis is confirmed, treatments are then decided. For CDH, infants require immediate intubation to prevent inflation, and then it can be surgically repaired. Other treatments include anti-seizure medications, surgery for gastro-intestinal (GI) malformations, and in some cases, referrals to other medical specialists. Developmental services may be recommended, for example help with feeding, motor adaptive control, and cognitive and speech/language therapy.³

Reproductive counselling is offered by genetic counsellors to families who are at risk of recurrent genetic disorders in future pregnancies. There will often be sessions where the genetic counsellor will discuss options for families who are considering having more children, including the choice of preimplantation genetic diagnosis (PGD). This process implies genetically testing the embryos obtained through in vitro fertilisation (IVF) before the implantation. PGD is a technique able to identify the genetic abnormalities carried by the embryo. Only embryos that do not display any abnormalities are implanted in the womb.⁶

Ethical, legal and social considerations

Every patient will deal with a negative prognosis differently. Multiple ethical factors will play a part in the decision of whether or not to terminate a pregnancy, including religious and personal beliefs. These factors can influence whether or not the decision is supported by the partner, potentially causing strains on relations if the opinions differ. Should the patient decide to carry on with the abortion, social groups may be recommended by the genetic counsellor for people dealing with the psychological effects of terminating a pregnancy. It’s important to highlight that balancing hope and realistic outcomes is a vital aspect of making an informed decision.⁹ 

Legal aspects are an important consideration in this process, as patients have multiple rights that must be observed. Patients are entitled to medical autonomy, which means that they have the right to choose what happens to their bodies – this includes whether or not they wish to undergo certain medical procedures, and have control over what happens to any blood or tissue that is collected from their body. They have the right to know all the facts and details of such procedures, including all risks and benefits of the treatments, as well as any alternatives available. Confidentiality and privacy are vital, meaning any sensitive or private information shared with healthcare professionals is protected, including details of genetic tests. Finally, every patient is entitled to accessing the same level of healthcare, regardless of factors such as gender and race.⁷

Genetic counsellors' final role in the process of diagnosing genetic disorders is providing support, as a diagnosis can have both, positive or negative emotional impact. A diagnosis can help patients understand the disorder and lead them to appropriate support groups. It can also allow other family members to become aware of the presence of the disorder, and make decisions about their own healthcare. In the future, they may decide to get tested to discover their own risk of conceiving a child with Fryns syndrome. It may also have negative emotions and cause patients to constantly fear losing their child due to the high mortality of the disorder. This may cause strains on relationships especially when discussing prenatal testing and termination of pregnancy. With a diagnosis, people are also able to look into charities and research, to learn what is happening in the field. This could potentially help people with any anxiety for the future of the disorder.⁸

Summary

To conclude, genetic counselling is a massive aspect when diagnosing rare genetic disorders, such as Fryns syndrome. This disorder has a high mortality rate because the symptoms impact vital physiological processes within the human body. Due to the complexity of the situation, genetic counsellors play an important role in reducing the stress and confusion of the family, and making an extremely difficult process much simpler. Scientific research is imperative to finding a way to decrease mortality rates in infants and improve disease management and treatment. Charities and support groups are very important for the affected families.