Introduction

Fryns syndrome is a rare genetic disorder that affects several organs of the body, causing a range of health problems. It is important to understand the diseases that might be similar to Fryns syndrome so that doctors can arrive at an appropriate diagnosis. Because many genetic illnesses have overlapping symptoms, clinicians use a differential diagnosis to rule out other ailments with characteristics similar to Fryns syndrome.

What Is Fryns Syndrome?

Fryns syndrome is a genetic condition that primarily affects the development of several parts of the body. People with Fryns syndrome often have abnormalities in their chest, lungs, diaphragm (the muscle that helps with breathing), and face.¹ Other common symptoms include:

• Diaphragmatic hernia: A hole in the diaphragm that allows organs like the stomach or intestines to move into the chest area
• Facial abnormalities: A wide face, flat nose, and wide-set eyes
• Lung problems: Underdeveloped lungs, which can make breathing difficult
• Growth problems: Both before and after birth, growth may be slower than normal
• Heart defects: Some people have heart conditions from birth

Since Fryns syndrome can affect various organs and cause multiple symptoms, it’s sometimes confused with other genetic disorders

What is the differential diagnosis of Fryn Syndrome?

Since it is a genetic disorder that causes symptoms across several organs to diagnose accurately could be a challenge. Some of the conditions include:²

Cornelia de Lange Syndrome (CdLS) syndrome causes facial abnormalities like a small head, long eyelashes, and thin lips; growth delay along with developmental delays; and intellectual disability. While both Fryns syndrome and CdLS have similar signs, there are key differences. Cornelia de Lange syndrome often has upper limb abnormalities, such as missing fingers or small hands, which are not typically seen in Fryns syndrome. CdLS also has more distinctive facial features, like arched eyebrows that meet in the middle.

DiGeorge Syndrome or 22q11.2 Deletion Syndrome has symptoms that are similar to Fryns syndrome like Heart defects, Facial abnormalities, and Intellectual disabilities. The biggest difference between Fryns syndrome and DiGeorge syndrome is the absence of a diaphragmatic hernia. DiGeorge syndrome also commonly leads to immune system problems, something not very typical of Fryns syndrome.

Pallister-Killian Syndrome or PKS shows similar symptoms to Fryns syndrome including facial abnormalities (wide-set eyes and flat nose), developmental delay, heart defects, and diaphragmatic hernia. Both conditions can have diaphragmatic hernia, but Pallister-Killian syndrome often has a “mosaic” pattern, meaning some cells have a different number of chromosomes. This can result in varying severity of symptoms. PKS also tends to feature streaks of darker or lighter skin, which is not a symptom of Fryns syndrome.

Meckel-Gruber Syndrome has symptoms similar to Fryns syndrome including diaphragmatic hernia, facial abnormalities, and cysts in the kidneys. Meckel-Gruber syndrome develops kidney cysts and issues with the brain, such as an abnormal cerebellum, which are not typical in Fryns syndrome. It also often leads to extra fingers or toes, a feature Fryns syndrome does not have.

Trisomy 18 or Edwards Syndrome has same symptoms similar to Fryns syndrome like growth delays, heart defects, developmental delays, and facial abnormalities. Patients with Trisomy 18 have clenched fists with overlapping fingers, a common trait not seen in Fryns syndrome. While both syndromes can include a diaphragmatic hernia, the survival rate and overall prognosis for babies with Trisomy 18 tend to be different, with more severe limitations on survival and developmental potential.

CHARGE Syndrome’s symptoms similar to Fryns syndrome are Heart defects, facial abnormalities, developmental delays, and growth delays. CHARGE syndrome stands out due to the presence of coloboma (a defect in the eye), which is not present in Fryns syndrome. CHARGE syndrome also typically involves ear abnormalities and hearing loss, neither of which are features of Fryns syndrome.

Bohring-Opitz Syndrome’s symptoms similar to Fryns syndrome are growth delays, heart defects, and facial abnormalities (like a prominent forehead and wide-set eyes). One key feature of Bohring-Opitz syndrome is the positioning of the arms and hands—babies often hold their arms in a flexed position. This condition also includes a characteristic posture that is not observed in Fryns syndrome. Intellectual disabilities are more severe in Bohring-Opitz syndrome.

Smith-Lemli-Opitz Syndrome has symptoms similar to Fryns syndrome like growth delays, facial abnormalities, developmental delays, and heart defects. Smith-Lemli-Opitz syndrome often involves issues with cholesterol metabolism, which is not a characteristic of Fryns syndrome. This condition also presents with genital abnormalities and extra toes, which are not seen in Fryns syndrome.

Congenital Diaphragmatic Hernia (CDH) without other syndrome has symptoms similar to Fryns syndrome like diaphragmatic hernia and lung underdevelopment. While a diaphragmatic hernia is a key feature of Fryns syndrome, many cases of congenital diaphragmatic hernia (CDH) occur without other associated syndromes. When CDH is not part of a syndrome like Fryns, there are usually fewer other developmental problems. Fryns syndrome, on the other hand, includes a wider array of issues beyond the diaphragm and lungs. 

Zellweger Syndrome’s symptoms similar to Fryns syndrome are developmental delays, facial abnormalities, and growth delays. Zellweger syndrome is part of a group of disorders called peroxisomal biogenesis disorders, which affect how the body breaks down certain fats and other substances. It often includes liver problems and high levels of certain chemicals in the blood, which are not features of Fryns syndrome.

How Is Fryns Syndrome Diagnosed?

To accurately diagnose Fryns syndrome depends on a combination of Physical Examination to Identify key physical characteristics like facial features and chest abnormalities. Imaging Tests like X-rays and ultrasounds to check for diaphragmatic hernia and organ development. Genetic Testing to look for specific genetic mutations, although no single gene has been conclusively linked to Fryns syndrome. Since there is no specific genetic test for Fryns syndrome yet, doctors focus on ruling out other conditions based on the combination of symptoms and tests.

Summary

Fryns syndrome is a complex genetic disorder with overlapping symptoms found in other conditions. Through a detailed process of differential diagnosis, doctors can rule out conditions that share similar features, such as Cornelia de Lange syndrome, DiGeorge syndrome, and Pallister-Killian syndrome, among others.

Understanding the differences between these conditions helps ensure that patients with Fryns syndrome get the correct diagnosis, leading to better management and care. With ongoing research and advances in genetic testing, doctors are improving their ability to diagnose Fryns syndrome and distinguish it from similar conditions.