Fryns syndrome is a multiple congenital anomaly syndrome usually resulting in neonatal death.
Description
Fryns syndrome is a genetic condition involving abnormalities in many organ systems that usually results in neonatal death. The condition was first reported in 1979 by J. P. Fryns.
Typical anomalies include a characteristic facial appearance, including a broad nasal bridge (part of the nose between the eyes), small jaw, abnormal ears, cleft palate, abnormal fingers, underdevelopment of the lungs, and abnormalities of the urogenital system (kidneys and genitals). Diaphragmatic hernia (opening in the diaphragm muscle that can allow contents of the lower abdomen like the liver or intestine or stomach to move up into the chest cavity through the hole) can also be seen in some cases. Some researchers believe that there may be a distinct subset of patients without diaphragmatic hernia who are more mildly affected.
Genetic profile
Fryns syndrome is inherited in an autosomal recessive manner. This means that two defective gene copies must be inherited, one from each parent, for the disease to manifest itself. Persons with only one gene mutation are carriers for the disorder. A person who is a carrier for Fryns syndrome does not have any symptoms and does not know he/she is a carrier unless he/she has had a child with Fryns syndrome. Carrier testing is not available since the gene location is not known at this time. The likelihood that each member of a couple would be a carrier for a mutation in the same gene is higher in people who are related (called consanguineous). When both parents are carriers for Fryns syndrome, there is a one in four chance (25%) in each pregnancy for a child to have the disease. There is a two in three chance that a healthy sibling of an affected child is a carrier.
There have been several different chromosome abnormalities reported with a Fryns syndrome–like appearance. Investigation for a candidate gene causing Fryns syndrome has not yet identified the causative gene.
Demographics
The number of affected individuals is reported as seven in 100,000. There does not appear to be any ethnic difference in prevalence. There are more than 50 documented cases of Fryns syndrome in the literature.
Signs and symptoms
The most frequent anomalies have been described as diaphragmatic defects, underdeveloped lungs, cleft lip and palate (usually on both sides, called bilateral), heart defects, cysts in the kidneys, urinary tract abnormalities, and limb underdevelopment.
Most patients also have underdeveloped external genitals, abnormal internal reproductive structures, abnormalities in the digestive tract, and abnormalities in the structure of the brain. Fewer patients have eye abnormalities.
Other reported anomalies include fetal hydops (fluid surrounding the fetus prenatally, usually fatal), prematurity, scoliosis (curvature of the spine), extra vertebrae or ribs, abnormal bone formation, and small chest cavity.
Diagnosis
Prenatal diagnosis has been possible in several fetuses by use of ultrasound to identify in one fetus fetal hydrops, diaphragmatic hernia, and dilation of the cerebral ventricles and in another with cystic hygroma and diaphragmatic hernia. These anomalies themselves can be isolated or as a part of another genetic syndrome; it is the specific combination of anomalies that would lead one to suspect Fryns syndrome. Definitive diagnosis is not possible until after birth or autopsy.
Treatment and management
Since Fryns syndrome is a genetic disease, caused by mutations in specific genes, there is no cure at this time. Some of the anomalies may be amenable to surgery, such as diaphragmatic hernia or cleft palate, but the entire prognosis for the baby must be considered.
Special education for mentally retarded individuals is indicated if the child survives.
Prognosis
Unfortunately, the prognosis for babies with Fryns syndrome is poor, with usual neonatal death occurring due to the lung hyperplasia and respiratory distress or other anomalies. Approximately 14% of infants survive the neonatal period. Survivors typically do not have complex heart malformations and less frequently have diaphragmatic hernias, milder lung hypoplasia, and neurologic impairment (usually severe to profound mental retardation with serious brain malformations).
PERIODICALS
Ramsing, M., et al. "Variability in the Phenotypic Expression of Fryns Syndrome: A Report of Two Sibships." American Journal of Medical Genetics 95 (2000): 415.
