Fryns syndrome

Description

Fryns syndrome is a condition that affects the development of many parts of the body.

Most people with Fryns syndrome have a defect in the muscle that separates the abdomen from the chest cavity (the diaphragm). The most common defect is a congenital diaphragmatic hernia, which is a hole in the diaphragm that develops before birth. This hole allows the stomach and intestines to move into the chest and crowd the heart and lungs. As a result, the lungs often do not develop properly (pulmonary hypoplasia), which can cause life-threatening breathing difficulties in affected infants.

People with Fryns syndrome typically have abnormalities of the fingers and toes and distinctive facial features. The tips of the fingers and toes tend to be underdeveloped, so they can look short and stubby and have small nails or no nails at all. Affected individuals may have widely spaced eyes (hypertelorism), a broad and flat nasal bridge, a thick nasal tip, a long space between the nose and upper lip (a long philtrum), a large mouth (macrostomia), and a small lower jaw (micrognathia). Many also have low-set and abnormally shaped ears.

Additional features of Fryns syndrome include small eyes (microphthalmia), clouding of the clear outer covering of the eye (the cornea), and an opening in the roof of the mouth (cleft palate) with or without a split in the lip (cleft lip). Fryns syndrome can also affect the development of the brain, heart, digestive system, kidneys, and genitalia.

Because there are significant health problems associated with congenital diaphragmatic hernias, most children with Fryns syndrome do not survive past infancy. Affected individuals who do survive into childhood often have severe developmental delays and intellectual disabilities.

The features of this condition often overlap with those of other disorders. As a result, Fryns syndrome can be difficult to diagnose.

Frequency

The exact prevalence of Fryns syndrome is unknown; fewer than 100 individuals with this condition have been reported in the medical literature. Studies suggest that up to 10 percent of all cases of congenital diaphragmatic hernia may be due to Fryns syndrome.

Causes

Variants (also called mutations) in the PIGN gene have been found to cause some cases of Fryns syndrome. The PIGN gene provides instructions for making an enzyme called GPI ethanolamine phosphate transferase 1. This enzyme takes part in a series of steps that produce a molecule called a glycophosphatidylinositol (GPI) anchor. The GPI anchor transports many different proteins to the cell membrane, ensuring that these proteins are available when needed.

The PIGN gene variants that cause Fryns syndrome are known as "loss-of-function variants" because they reduce the amount of functional GPI ethanolamine phosphate transferase 1 enzyme that is available to modify the GPI anchor. As a result, the GPI anchor cannot deliver proteins to their proper places on the cell membrane. This disrupts critical developmental pathways, which leads to the signs and symptoms seen in people with Fryns syndrome.

Researchers are trying to determine other possible genetic causes for Fryns syndrome. Chromosomal changes, such as missing (deleted) chromosomal material, that can cause features similar to those seen in people with Fryns syndrome are of particular interest to investigators.

Inheritance

Fryns syndrome appears to be inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Autosomal recessive inheritance. Credit: U.S. National Library of Medicine.

Other Names for This Condition

• Diaphragmatic hernia, abnormal face, and distal limb anomalies
• Diaphragmatic hernia-facial dysmorphism-distal limb anomalies syndrome

Where this page came from

This page was imported from MedlinePlus Genetics, National Library of Medicine. Courtesy of MedlinePlus from the National Library of Medicine; its genetics summaries and the illustrations credited to the library are in the public domain. Pictures credited to others are not copied.

Nobody has written it yet — it is the source material at a new address, which is why search engines are asked to skip it and why no one earns from it. It is up for grabs: take it on, and it is yours to rewrite and to earn from.