What are the other Names for this Condition? (Also known as/Synonyms)

• Diaphragmatic Hernia, Abnormal Face, and Distal Limb Anomalies
• Moerman Van Den Berghe Fryns Syndrome

What is Fryns Syndrome? (Definition/Background Information)

• Fryns Syndrome is a highly infrequent genetic developmental disorder that affects multiple organs of the body. It is congenital in nature and infants (and fetuses) affected by this syndrome, typically have a high mortality rate
• Fryns Syndrome is autosomal recessive, implying that the defective gene has to be inherited from both parents to cause the condition. The gene causing the disorder has not yet been identified
• Characteristic features of this abnormality include: Underdeveloped diaphragm leading to severe hernia, abnormal facial appearance, malformed lungs and limbs
• Symptomatic treatment and support of Fryns Syndrome is provided on a case-by-case basis. The prognosis for Fryns Syndrome is generally dismal

Who gets Fryns Syndrome? (Age and Sex Distribution)

• The incidence of Fryns Syndrome is extremely rare (less than 100 cases have been reported worldwide)
• It is believed to affect both male and female sex population uniformly
• There is insufficient information on any specific racial or ethnic preference

What are the Risk Factors for Fryns Syndrome? (Predisposing Factors)

The risk factors of Fryns Syndrome are:

• Fryns Syndrome runs in the families and hence, children born in families having a previous medical history of the condition, are at risk
• Individuals suffering from congenital diaphragmatic hernia (CDH), in which malformation of the diaphragm membrane separating the abdomen from the pulmonary region occurs, have a high risk. About 1 in 10-75 children with CDH, are noted to have Fryns Syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Fryns Syndrome? (Etiology)

• Researchers believe that Fryns Syndrome is caused by the inheritance of an autosomal recessive gene
• Medical research is yet to identify the specific gene, causing the disorder

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Fryns Syndrome?

Signs and symptoms of Fryns Syndrome are numerous since the condition affects multiple regions of the body. Due to this, the syndrome is also known as, ‘Diaphragmatic Hernia, Abnormal Face, and Distal Limb Anomalies’. The main features include the following:

• Defects of the diaphragm: There may be an absent or underdeveloped diaphragm, causing a diaphragmatic hernia
• Abnormal facial appearance that includes:
  • Coarse features
  • Broad or flat nose
  • Malformed ears that are set lower (than the regular location)
  • Wide mouth, undersized jaw
  • Widely set eyes
  • Increased distance between the mouth and nose
• Incomplete development of fingers and nails
• Significantly underdeveloped lungs
• A few minor features that include:
  • Eye disorder, such as clouded eyes
  • Malformed kidneys, brain, genitals
  • Abnormally developed gastrointestinal system, cardiovascular system

How is Fryns Syndrome Diagnosed?

Diagnostic tests for detecting Fryns Syndrome may be performed on developing fetus in pregnant women, or on a newborn child. Since the genes associated with this disorder are unknown, genetic testing and analysis is not currently possible. The main diagnostic tests include:

• Physical examination of the newborn child: 3 or 4 of the key features (out of a set of 6) must be present, for the disorder to be classified as Fryns Syndrome. These include:
  • Diaphragmatic hernia
  • Abnormal facial appearance
  • Distal digital hypoplasia (malformed digits)
  • Significantly underdeveloped lungs (pulmonary hypoplasia)
  • Presence of a member, such as a parent (with family history indicating the condition), or a sibling having the condition
  • Malformation of any one of the following: Brain, cardiovascular system, GI system, genitals, eyes (cloudy cornea), lips and palate (orofacial cleft), kidney dysplasia, or excess amniotic fluid
• Ultrasonography, which is performed prenatally
• MRI scan of the fetus
• Evaluation of the family medical history; presence of an affected sibling or cousin, or the establishment of consanguineous parents or spouses

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Fryns Syndrome?

Considering the fact that most of the major organs and systems are severely affected, the complications of Fryns Syndrome are many. The major body systems and organs affected are:

• Heart and blood vessels
• Gastrointestinal tract
• Kidneys
• Brain and central nervous system
• Pulmonary system

Most cases of Fryns Syndrome are fatal within the initial few months, following delivery.

How is Fryns Syndrome Treated?

Treatment of Fryns Syndrome is undertaken on a case-by-case basis, after carrying out a detailed evaluation of the infant child. Symptomatic treatment and management of the presentations are followed. The treatment measures could include:

• Surveillance and close monitor of the newborn, by a team of healthcare experts is carried out. A treatment regimen addressing each infant’s condition, is then planned and undertaken
• The diaphragmatic hernia condition demands urgent attention. Bowel inflation during breathing will cause additional complications and hence, treatment to decrease air accumulation may be needed
• Prior to any surgical correction of the malformed diaphragm, the newborn is stabilized through intensive medical therapy

How can Fryns Syndrome be Prevented?

• Currently, there are no specific methods or guidelines to prevent Fryns Syndrome genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

What is the Prognosis of Fryns Syndrome? (Outcomes/Resolutions)

• Fryns Syndrome is a fatal genetic disorder with extremely poor prognosis. Most fetuses are aborted naturally with many babies being stillborn. A majority of the infants, who are born, die during the initial few months, due to severe complications
• The children who survive the initial phase (into early adolescence),  are severely affected by birth defects and developmental deformities
• The prognosis is dependent upon the severity and number of malformations present. Generally, individuals without a diaphragmatic hernia problem, do slightly better

Additional and Relevant Useful Information for Fryns Syndrome:

In a study population in a particular region in France, the incident rate of Fryns Syndrome was peculiarly observed to be around 1 in 14,000. The reason for increased incidence in this region is unknown.