Introduction

Overview of Fryns syndrome (FS) 

Fryns syndrome (FS) is a rare condition present from birth which is caused by changes in the baby’s genes that are inherited from both parents during the pregnancy.^1,2 The disorder can lead to multiple birth defects and usually causes death very soon after the baby is born.¹ Although, there have been a few cases of babies surviving into childhood.³

The range and severity of symptoms in FS can affect the baby’s survival and are believed to be influenced by the genetic changes inherited by the baby.^1,3 However, some of the symptoms that can appear in FS include:^1,3,5

• Defects in the diaphragm including hernia in the diaphragm (congenital diaphragmatic hernia)
• Incomplete development of the baby’s lungs (Pulmonary hypoplasia)
• Unusual changes to the baby’s facial features
• Disproportionately short fingers and toes⁴
• Clouding of the lens in the eye
• Disorders that affect the brain, nerves and/or spinal cord
• Problems with the digestive system

Given that congenital (which means present from birth) diaphragmatic hernia (CDH) is one of the most common symptoms of FS and can reduce the chances of survival in a baby with FS, this article will provide more information on CDH and the management of the condition.²

Congenital diaphragmatic hernia (CDH) 

The diaphragm is a thin muscle which moves up and down to help you breathe and separates the organs in the chest from the belly. There are 4 key structures which make up the diaphragm and each needs to develop properly during pregnancy for the diaphragm to form correctly and carry out its function.⁷

However, there are rare instances where there are issues in the development of these structures, leading to a gap or a weak area of varying sizes in the diaphragm instead.^6,7 This can cause the organs in the belly such as the stomach, liver and intestines to move through the gap or weak area into the chest area.⁶ When this rare instance occurs, it is known as CDH and can be seen in the baby while it is still in the womb using ultrasound imaging.^2,6,7

The specific genes associated with the development of CDH in FS are unknown.² However, 50% of individuals with FS who have harmful changes to a gene called PIGN, have been found to develop CDH.²

An illustration of the internal arrangement of a baby’s organs with and without CDH is seen in Figure 1. The location of the diaphragmatic hernia can vary but it is commonly located on the left side towards the back of the baby’s body in FS.^2,8

Figure 1: A depiction of the internal differences between a newborn baby with the correct development and a newborn baby with diaphragmatic hernia created with BioRender.com.

The newborn baby on the left has an intact diaphragm and all of the organs are arranged in the correct place. The newborn baby on the right has a gap in the diaphragm which has allowed the baby’s organs to move through and reside in the wrong places. 

As the organs from the belly can move into the chest area in CDH, they interfere with the development of the organs in the body. For example, these changes can prevent the lungs from growing properly which can significantly reduce the baby’s survival.^8,9 This is the basis for some of the symptoms of CDH highlighted below that a baby can present with.^7,8

Signs and symptoms of CDH

• Respiratory distress ranging from mild to severe
• Incomplete or smaller development of the baby’s lungs (pulmonary hypoplasia)
• The blood vessels in the lungs do not develop properly which leads to high blood pressure within the lungs (pulmonary hypertension)
• Blue/grey skin or lips (Cyanosis)
• Differences in the breathing and heart sounds
• The front of the baby’s belly is sunken in (scaphoid abdomen)
• Feeding problems 

CDH can be diagnosed by:^{2,6, 8}

• Ultrasound scans: usually from the second trimester of the pregnancy (13-27 weeks pregnant) or later if the CDH is small
• Foetal MRI scans
• Chest and belly radiographs

Frequency of CDH in FS

CDH is very common in FS with over 90% of babies presenting with it as a  symptom of FS.²There is limited recent data on the frequency of CDH in FS in live births but a previous study has showed that 23 out of 1,833 persons were observed to have FS with CDH over a 6 year period.² Considering that CDH is present in around 1 to 4 babies per 10,000 live births in the general population highlights how common CDH in FS is.^6,8 It must be noted that despite how common CDH presents in babies with FS, having CDH does not automatically mean the baby has FS.² Additional testing is required to confirm FS diagnosis. It is also unclear whether one gender is at higher risk of developingCDH than the other.⁸

Management and treatment strategies of CDH in Fryns Syndrome

There are a few options to manage the baby’s CDH symptoms which will be discussed below. The location and extent of the CDH symptoms affecting the baby has an impact on the baby’s survival.⁸ Additionally, some of the management or treatment strategies may not always be possible due to the additional symptoms of FS which can complicate care.

Prenatal management 

There are some prenatal (while the baby is still in the womb) options, though some are still being assessed for effectiveness in clinical trials:^2,8

• Surgery to repair the CDH followed by careful monitoring
• Fetoscopic tracheal balloon occlusion (FETO)
• FETO is a procedure that can be performed on the baby and can be used to help with the development of the lungs so they can be an adequate size by birth.⁸ While the baby is in the womb, the lungs produce fluid which is useful for the lungs to grow but can also flow out of the baby’s mouth. In CDH where the lungs are underdeveloped or smaller than usual, surgery can be performed where an inflatable balloon is temporarily inserted into the baby’s windpipe.⁸ This action causes the lung fluid to remain inside the baby, allowing it to build up and stretch the lungs and encourage them to grow.⁸ However, this procedure can increase the risk of premature birth which may have a negative impact on the baby’s survival⁸

Postnatal management 

The management strategies after the birth of the baby are as follows:^2,7,8

Airway and digestive management

Nasogastric tubes can be inserted through the nose to the stomach to reduce the pressure inside the stomach and intestine. A breathing tube can be inserted to prevent air from going into the bowels which are positioned in the wrong place. Although, the changes to the babies facial structure and features in FS may complicate the use of these tubes.¹⁰

Extracorporeal membrane oxygenation (ECMO)A machine that can be used on the baby if necessary which acts as a life support system by temporarily acting as lungs for the baby.

• Inhaled nitric oxide

A medicine which can have an impact on the high blood pressure in the lungs.

• Surgery to repair CDH 

Surgery can also be performed on the baby after they have been delivered to repair CDH but it is performed after the high blood pressure in the lungs, if present, has been controlled. This depends on the size of the gap if it can be repaired. The surgery is minimally invasive meaning it will involve small cuts and has a quick recovery time. The surgery involves covering the gap with a patch or flap designed with various materials such as synthetic or the baby’s belly muscle.

FAQs

If the management or treatment of CDH is successful, does that mean that the baby will survive with Fryns syndrome?

While managing CDH may slightly improve the baby’s chances of survival, Fryns syndrome involves multiple other serious conditions which can still put the baby at high risk. Addressing CDH alone does not resolve the other challenges faced by the baby for survival. 

Summary

FS is a rare and life-threatening condition in babies as a result of inheriting genetic changes from both parents. CDH is one of the most common symptoms of FS although the genetic changes which cause CDH in FS are not clear. The management of CDH can have a positive impact on the baby’s survival. There are a few management options that can be considered both before and after the baby is born. However, it should be noted that some may be still under testing in clinical trials for effectiveness or may not be suitable for babies with FS due to the complications of the syndrome.