Fryns syndrome

Other Names: Moerman Van den berghe Fryns syndrome; FRNS; Diaphragmatic hernia, abnormal face, and distal limb anomalies

Fryns syndrome is a condition that affects the development of many parts of the body. The features of this disorder vary widely among affected individuals and overlap with the signs and symptoms of several other disorders. These factors can make Fryns syndrome difficult to diagnose.

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. Most people with Fryns syndrome die before birth or in early infancy from pulmonary hypoplasia caused by a congenital diaphragmatic hernia. However, a few affected individuals have lived into childhood. Many of these children have had severe developmental delay and intellectual disability.

Epidemiology

The worldwide incidence of Fryns syndrome is unknown. More than 50 affected individuals have been reported in the medical literature. Studies suggest that Fryns syndrome occurs in 1.3 to 10 percent of all cases of congenital diaphragmatic hernia.

Cause

The cause of Fryns syndrome is unknown. The disorder is thought to be genetic because it tends to run in families and has features similar to those of other genetic disorders. Duplications and deletions in several chromosome regions have been associated with congenital diaphragmatic hernia and some of the other features of Fryns syndrome. However, no specific genetic change has been found to cause all of the signs and symptoms of this disorder.

Inheritance

Autosomal recessive inheritance, a 25% chance

Fryns syndrome appears to be inherited in an autosomal recessive pattern, which means both copies of a gene in each cell have mutations. However, no associated gene has been identified. 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.

Signs and symptoms

Many indiivduals with this condition have defects of the diaphragm such as a congenital diaphragmatic hernia (a hole in the diaphragm present at birth). Other major signs of Fryns syndrome include abnormalities of the fingers and toes and distinctive facial features. The tips of the fingers and toes tend to be underdeveloped, resulting in a short and stubby appearance with small or absent nails. Most affected individuals have several unusual facial features, including widely spaced eyes (hypertelorism), a broad and flat nasal bridge, a thick nasal tip, a wide space between the nose and upper lip (a long philtrum), a large mouth (macrostomia), and a small chin ([[micrognathia[[). Many also have low-set and abnormally shaped ears. Several additional features have been reported in people with Fryns syndrome. These 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, cardiovascular system, gastrointestinal system, kidneys, and genitalia.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Aplasia/Hypoplasia of the nipplesAbsent/small nipples
• Broad forehead(Increased width of the forehead)
• Congenital diaphragmatic hernia
• High palate(Elevated palate)
• Hypoplastic fingernail(Small fingernail)
• Intellectual disability(Mental deficiency)
• Long philtrum
• Low-set, posteriorly rotated ears
• Micrognathia(Little lower jaw)
• Multicystic kidney dysplasia
• Pulmonary hypoplasia(Small lung)
• Severe global developmental delay
• Short neck(Decreased length of neck)
• Tented upper lip vermilion
• Wide nasal bridge(Broad nasal bridge)

30%-79% of people have these symptoms

• Abnormal cardiac septum morphology
• Agenesis of corpus callosum
• Anteverted nares(Nasal tip, upturned)
• Cerebral cortical atrophy(Decrease in size of the outer layer of the brain due to loss of brain cells)
• Cleft palate(Cleft roof of mouth)
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Coarse facial features(Coarse facial appearance)
• Corneal opacity
• Cryptorchidism(Undescended testes)
• Hypertelorism(Wide-set eyes)
• Median cleft lip(Central cleft upper lip)
• Non-midline cleft lip
• Polyhydramnios(High levels of amniotic fluid)
• Seizure
• Short distal phalanx of finger(Short outermost finger bone)
• Tetralogy of Fallot
• Thickened nuchal skin fold(Thickened skin folds of neck)
• Wide intermamillary distance(Wide-spaced nipples)
• Wide mouth(Broad mouth)

Diagnosis Diagnosis of Fryns syndrome should be suspected in individuals with the following clinical and laboratory findings.

Clinical findings

• Diaphragmatic defects including diaphragmatic hernia in any location (most commonly a posterolateral Bochdalek hernia), diaphragmatic eventration, significant diaphragm hypoplasia, or diaphragm agenesis
• Characteristic facial appearance with a coarse face, wide-set eyes, a wide and depressed nasal bridge with a broad nasal tip, a long philtrum, low-set and anomalous ears, a tented vermilion of the upper lip, wide mouth, and a small jaw
• Short distal phalanges of the fingers and toes. The nails may also be small.
• Pulmonary hypoplasia of a significant degree. This clinical finding can accompany diaphragmatic hernia.

Characteristic associated anomalies including at least one of the following:

• Polyhydramnios
• Cloudy corneas and/or microphthalmia
• Orofacial clefting
• Brain malformations including hydrocephalus, abnormalities of the corpus callosum, and Dandy-Walker malformation
• Cardiovascular malformation
• Renal dysplasia / renal cortical cysts
• Gastrointestinal malformation
• Genital malformation

Family history consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Absence of a known family history does not preclude the diagnosis. Laboratory findings. Absence of a copy number variant associated with congenital diaphragmatic hernia, including chromosome deletions at 15q26.2 and 8p23.1 and mosaic trisomy 1q .

Treatment

For congenital diaphragmatic hernia, the neonate is immediately intubated to prevent inflation of herniated bowel, surgery, and/or supportive measures as for the general population. Standardized treatment with anti-seizure medications by an experienced neurologist. Additional anomalies may require consultations and management by ophthalmology, cardiology gastroenterology, nephrology, urology, and craniofacial specialists. Developmental services as needed including feeding, motor, adaptive, cognitive, and speech/language therapy. Assess for new onset of seizures. Monitor developmental progress and educational needs. Follow up with ophthalmology, cardiology, gastroenterology, nephrology, urology, and craniofacial specialists as needed.

NIH genetic and rare disease info

• NIH info on Fryns syndrome

Fryns syndrome is a rare disease.

Fryns syndrome Resources
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