Fryns syndrome is an extremely rare inherited disorder characterized by multiple abnormalities that are present at birth (congenital). Characteristic symptoms and physical findings include protrusion of part of the stomach and/or small intestines into the chest cavity (diaphragmatic hernia), abnormalities of the head and face area (craniofacial region), and underdevelopment of the ends of the fingers and toes (distal digit hypoplasia). Additional symptoms include underdevelopment (hypoplasia) of the lungs, incomplete closure of the roof of the mouth (cleft palate), cardiac defects, and varying degrees of mental retardation. Fryns syndrome is inherited as an autosomal recessive trait.
Fryns syndrome is associated with numerous abnormalities of varying severity such as protrusion of part of the stomach and/or small intestines into the chest cavity (diaphragmatic hernia), unusual facial features, and abnormalities of the fingers and toes. The number and severity of symptoms and physical findings will vary greatly from case to case.
Some symptoms such as diaphragmatic hernia, underdevelopment of the lungs, and cardiac defects may result in life-threatening complications during the newborn (neonatal) period.
Approximately 89 percent of all infants with Fryns syndrome have diaphragmatic hernia of varying degrees of severity. Lung hypoplasia and deformity of the lobes of the lungs also occurs in most cases. In some cases, affected infants may also have an abnormally small upper chest (thorax) and abnormal accumulation of milky fluid (chyle) in the thorax (chylothorax). Cases of Fryns syndrome in which affected infants do not have diaphragmatic hernia are considered less severe.
Infants with Fryns syndrome also have characteristic facial features that give the face a coarse appearance. These features include an abnormally small jaw (micrognathia) that may be displaced father back than normal (retrognathia); a broad, flat nasal bridge; an abnormally wide mouth (macrostomia); and incomplete closure of the roof of the mouth (cleft palate). In addition, affected infants may also have cloudy lenses of the eyes (corneal clouding); malformation (dysplasia) of the outer ears (pinnae) with underdeveloped lobes; an abnormal groove in the upper lip (cleft lip); a large, upturned nose; and a short, broad neck.
Another characteristic symptom of Fryns syndrome is underdevelopment of the tips of the fingers and toes (distal digit or acral hypoplasia). Affected infants may have underdeveloped or absent nails, abnormally short bones in the tips of the fingers and toes (terminal phalanges), and permanently flexed fingers (camptodactyly).
Affected infants may also have various abnormalities affecting the central nervous system. In approximately 50 percent of cases, Dandy-Walker malformation may be present. Dandy-Walker malformation is a rare malformation of the brain characterized by an abnormally enlarged space at the back of the brain (cystic 4th ventricle) that interferes with the normal flow of cerebrospinal fluid through the openings between the ventricle and other parts of the brain. In many cases, an abnormal cystic growth consisting of dilated lymph vessels beneath the skin in the neck area (cystic hygroma) may be present. Affected infants may also exhibit absence of the thick band of nerve fibers that connects the left and right hemispheres of the brain (agenesis of the corpus callosum), accumulation of excessive cerebrospinal fluid in the skull (hydrocephalus), and absence of a structure of the brain (rhinecephalon) associated with the sense of smell (arrhinencephaly). For more information on these disorders, choose “Hydrocephalus” “Dandy Walker” and “Agenesis of Corpus Callosum” as your search terms in the Rare Disease Database.)
Approximately 55 percent of infants with Fryns syndrome exhibit congenital heart (cardiac) defects including atrial and ventricular septal defects (VSDs and ASDs). These septal defects are the most common structural heart defects. ASDs are characterized by an abnormal opening in the fibrous partition (septum) that separates the two upper chambers (atria) of the heart. VSDs are characterized by an abnormal opening in the septum that divides the heart’s two lower chambers (ventricles).
Skeletal abnormalities may be present in some infants with Fryns syndrome including abnormal side-to-side curvature of the spine (scoliosis), extra ribs, and (osteochondrodysplasia).
Some infants with Fryns syndrome may have abnormalities of the genitourinary system. Females may exhibit malformation of the uterus with unusual “horn-shaped” branches (bicornuate uterus) and underdeveloped ovaries. Males may experience failure of one or both testes to descend into the scrotum (cryptorchidism) and placement of the urinary opening on the underside of the penis (hypospadias). Kidney (renal) abnormalities may also be present including cysts in the kidneys and malformation (dysplasia) of the kidneys.
Digestive abnormalities secondary to diaphragmatic hernia may also occur in some infants with Fryns syndrome including twisting (malrotation) of the intestines, protrusion of part of the intestines through an abnormal opening near the umbilical cord (omphalocele), esophageal atresia, and/or imperforate anus. Esophageal atresia is a condition in which the tube that carries food from the mouth to the stomach (esophagus) ends in a pouch instead of connecting to the stomach. Imperforate anus is a rare condition in which a thin covering (membrane) blocks the anal opening or the passage that connects the anus and the lowest part of the large intestine (rectum) fails to develop.
Fryns syndrome is inherited as an autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
In recessive disorders, the condition does not occur unless an individual inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
Parents of several individuals with the disorder have been closely related (consanguineous). If both parents carry the same disease gene, then there is a higher-than-normal risk that there children may inherit the two genes necessary for the development of the disorder.
Fryns syndrome affects males and females in equal numbers. More than 50 cases have been reported in the medical literature. One estimate suggests that the prevalence of Fryns syndrome is .7 of every 10,000 births.
Fryns syndrome was first identified in 1979 by Dr. J.P. Fryns.
In some cases, Fryns syndrome may be suspected before birth (prenatally) based upon results of fetal ultrasonography, a specialized imaging technique in which sound waves are used to create an image of the developing fetus. A diagnosis of Fryns syndrome may be considered due to the presence of an abnormal cystic growth consisting of dilated lymph vessels in the neck area (cystic hygroma), diaphragmatic hernia, and excessive amniotic fluid surrounding the fetus within the amniotic sac (polyhydramnios).
A diagnosis of Fryns syndrome may be confirmed after birth (postnatally) based upon a thorough clinical evaluation, identification of characteristic physical features, and advanced imaging techniques.
The treatment of Fryns syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Surgical correction of internal malformations such as diaphragmatic hernia may be performed.
Infants with a diagnosis of Fryns syndrome may receive thorough examination to determine whether neurological or cardiac abnormalities often associated with Fryns syndrome are present.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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