National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Fryns Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
Related Disorders List
Information on the following diseases can be found in the Related Disorders section of this report:
- Trisomy 18 Syndrome
- Pallister Killian Mosaic Syndrome
- Cornelia de Lange Syndrome
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.
Symptoms of the following disorders can be similar to those of Fryns syndrome. Comparisons may be useful for a differential diagnosis:
Trisomy 18 syndrome is a rare chromosomal disorder in which all or a critical region of chromosome 18 appears three times (trisomy) rather than twice in cells of the body. In some cases, the chromosomal abnormality may be present in only a percentage of cells, whereas other cells contain the normal chromosomal pair (mosaicism). Depending on the specific location of the duplicated (trisomic) portion of chromosome 18--as well as the percentage of cells containing the abnormality--symptoms and findings may be extremely variable from case to case. However, in many affected infants, such abnormalities may include growth deficiency, feeding and breathing difficulties, developmental delays, mental retardation, and, in affected males, undescended testes (cryptorchidism). Individuals with Trisomy 18 syndrome may also have distinctive malformations of the head and facial (craniofacial) area, such as a prominent back portion of the head; low-set, malformed ears; an abnormally small jaw (micrognathia); a small mouth with an unusually narrow roof (palate); and an upturned nose. Affected infants may also have narrow eyelid folds (palpebral fissures), widely spaced eyes (ocular hypertelorism), and drooping of the upper eyelids (ptosis). Malformations of the hands and feet are also often present, including overlapped, flexed fingers; webbing of the second and third toes; and a deformity in which the heels are turned inward and the soles are flexed (clubfeet [talipes equinovarus]). Infants with Trisomy 18 syndrome may also have structural heart (cardiac) defects at birth (congenital) including an abnormal opening in the partition dividing the lower chambers of the heart (ventricular septal defect) or persistence of the fetal opening between the two major arteries (aorta, pulmonary artery) emerging from the heart (patent ductus arteriosus). (For more information on this disorder, choose "Trisomy 18 Syndrome" as your search term in the Rare Disease Database.)
Pallister-Killian mosaic syndrome is a rare inherited disorder characterized by characteristic facial features, mental retardation, and seizures. Characteristic facial features give infants with this disorder a coarse facial appearance. Such features include a broad, flat nasal bridge; prominent forehead; and widely spaced eyes (hypertelorism). In addition, infants with Pallister-Killian syndrome may have diaphragmatic hernia, Dandy-Walker malformation, congenital heart defects, and skin abnormalities. Pallister-Killian mosaic syndrome is caused by tetrasomy for chromosome 12p. Infants with Pallister-Killian mosaic syndrome have four copies of the short arm of chromosome 12 instead of the normal two. (For more information on this disorder, choose "Pallister-Killian" as your search term in the Rare Disease Database.)
Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that is apparent at birth (congenital). Associated symptoms and findings typically include delays in physical development before and after birth (prenatal and postnatal growth retardation); characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance; malformations of the hands and arms (upper limbs); and mild to severe mental retardation. Many infants and children with the disorder have an unusually small, short head (microbrachycephaly); an abnormally long vertical groove between the upper lip and nose (philtrum); a depressed nasal bridge; upturned nostrils (anteverted nares); and a protruding upper jaw (maxillary prognathism). Additional, characteristic facial abnormalities may include thin, downturned lips; low-set ears; arched, well-defined eyebrows that grow together across the base of the nose (synophrys); an unusually low hairline on the forehead and the back of the neck; and abnormally curly, long eyelashes. Affected individuals may also have distinctive malformations of the limbs, such as unusually small hands and feet, inward deviation (clinodactyly) of the fifth fingers, or webbing (syndactyly) of certain toes. The range and severity of associated symptoms and findings may be extremely variable from case to case. (For more information on this disorder, choose "Cornelia de Lange Syndrome" as your search term in the Rare Disease Database.)
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.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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For information about clinical trials sponsored by private sources, contact:
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FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:229850; Last Update:9/18/00.
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