Meckel syndrome is a rare inherited disorder characterized by abnormalities affecting several organ systems of the body (multisystem). Three classic symptoms are normally associated with Meckel syndrome: protrusion of a portion of the brain and its surrounding membranes (meninges) through a defect in the back or front of the skull (occipital encephalocele), multiple cysts on the kidneys (polycystic kidneys), and extra fingers and/or toes (polydactyly). Affected children may also have abnormalities affecting the head and face (craniofacial area), liver, lungs, and genitourinary tract. Meckel syndrome is inherited as an autosomal recessive trait.
The specific symptoms associated with Meckel syndrome vary greatly from one individual to another. Affected children will not have all of the symptoms detailed below. Central nervous system, pulmonary or kidney abnormalities may result in life-threatening complications during infancy or childhood.
The most common central nervous system abnormality associated with Meckel syndrome is occipital encephalocele, a condition in which an infant is born with a gap in the skull (i.e., a part of one or more of the plates that form the skull does not seal). The membranes that cover the brain (meninges) and brain tissue often protrude through this gap. Occipital encephalocele may result in swelling or infection of the meninges and accumulation of excessive cerebrospinal fluid (CSF) in the skull, which causes pressure on the tissues of the brain (hydrocephaly). Additional central nervous system abnormalities that may occur in infants with Meckel syndrome include incomplete development of parts of the brain (anencephaly), Arnold-Chiari malformation, Dandy-Walker malformation, and a condition known as microcephaly, which indicates that the head circumference is smaller than would be expected for age and sex. (For more information on these conditions, see the Related Disorders section below.)
Affected infants may have distinctive facial features including an abnormally small jaw (micrognathia); larged, low-set and malformed ears; cleft palate; cleft lip; sloping forehead; and short neck. Affected children may have eye (ocular) abnormalities including widely spaced eyes (hypertelorism), abnormally small eyes (microphthalmia), and underdevelopment of the nerves of the eyes (optic nerve hypoplasia). In some cases, the eyeball may fail to close or a cleft may form resulting in a keyhole-shaped pupil (iris coloboma).
Multiple cysts on the kidneys (polycystic kidneys) is the most common symptom associated with Meckel syndrome. The condition is characterized by normal kidney tissue that is replaced by fluid-filled sacs or cysts of varying sizes that become larger (10-20 times greater than normal) as the disease progresses. Findings associated with polycystic kidneys include abnormally high blood pressure (hypertension) and the progressive loss of kidney function, leading to end-stage renal failure. Improper kidney function may also result in a reduction in the amount of amniotic fluid surrounding the developing fetus (oligohydramnios).
Affected individuals may also have extra fingers and toes, most often extra fingers on the “pinky” side of the hands (postaxial polydactyly). Additional skeletal malformations include bowing of the long bones of the arms and legs, permanent fixation of the fifth fingers in a bent position (clinodactyly), webbing of the fingers and toes (syndactyly), and a form of club foot where the heel of the foot may be turned inward toward the body while the rest of the foot is bent downward and inward (talipes equinovarus).
In some cases, abnormalities of the genitourinary tract may be present including failure of the one or both testes to descend into the scrotum (cryptorchidism), underdeveloped (hypoplastic) bladder, and incomplete development of genitalia.
Some affected infants may have abnormalities affecting other organs of the body including the liver, lungs or heart. The liver may be abnormally enlarged (hepatomegaly) with multiple cysts and excessive fibrous tissue (fibrosis). Widening (dilatation) and fibrosis of the passages that carry bile from the liver to the small intestines (bile ducts) may also occur. The lungs may be underdeveloped (hypoplastic) and the structure that covers the entrance of the larynx when swallowing may be clefted (cleft epiglottis). The spleen may be abnormally enlarged (splenomegaly) or missing (asplenia).
Heart abnormalities may include atrial and ventricular septal defects (ASDs and VSDs) and patent ductus arteriosus. 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). The size, location, and nature of a septal defect and any associated abnormalities determine the severity of symptoms. Patent ductus arteriosus is a condition in which the passage (ductus) between the blood vessel that leads to the lungs (pulmonary artery) and the major artery of the body (aorta) fails to close after birth.
Meckel syndrome is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal 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 for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.
Cases of Meckel syndrome may result due to mutations of a different disease gene or genes (genetic heterogeneity). Consequently, the specific characteristics associated with Meckel syndrome will vary from case to case. Meckel syndrome may be associated with genes located on three different chromosomes (17, 11, and 8). Cases associated with chromosome 17 may be referred to as Meckel syndrome type 1. Cases associated with chromosome 11 may be referred to as Meckel syndrome type 2. Cases associated with chromosome 8 may be referred to as Meckel syndrome type 3.
Investigators have determined that some cases of Meckel syndrome are caused by disruption or changes (mutations) of a gene located on the long arm (q) of chromosome 17 (17q22-q23). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 17q22-q23” refers to bands 22-23 on the long arm of chromosome 17. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Investigators have determined that some cases of Meckel syndrome are caused by disruption or changes (mutations) of a gene located on the long arm (q) of chromosome 11 (11q13).
Investigators have determined that some cases of Meckel syndrome are caused by disruption or changes (mutations) of a gene located on the long arm (q) of chromosome 8 (8q24).
Meckel syndrome affects males and females in equal numbers. More than 200 cases have been reported in the medical literature. The incidence of Meckel syndrome is estimated in various areas around the world to be 1 in 13,250 to 1 in 140,000 live births. The disorder is more common in the Finnish population, with an incidence of 1 in 9000.
A diagnosis of Meckel syndrome is made based upon a thorough clinical evaluation, detailed patient history, and a variety of specialized tests. Prenatal diagnosis is available through ultrasonography, which can detect certain abnormalities (e.g., encephalocele, microcephaly, oligohydramnios). Magnetic resonance imaging (MRI) may be used in conjunction with ultrasonography. Chromosomal analysis may be performed to rule out trisomy 13.
The treatment of Meckel syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, who diagnose and treat heart abnormalities (cardiologists), skeletal abnormalities (orthopedists), hearing problems (audiologists), urinary tract abnormalities (urologists), kidney malformations (nephrologists), and other healthcare professionals may need to systematically and comprehensively plan an affected child's treatment.
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.
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Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.
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