|55 Kenosia Avenue
Danbury, CT 06810
Toll Free: 1.800.999.6673
The National Organization for Rare Disorders (NORD) web site, its databases, and the contents thereof are copyrighted by NORD. No part of the NORD web site, databases, or the contents may be copied in any way, including but not limited to the following: electronically downloading, storing in a retrieval system, or redistributing for any commercial purposes without the express written permission of NORD. Permission is hereby granted to print one hard copy of the information on an individual disease for your personal use, provided that such content is in no way modified, and the credit for the source (NORD) and NORD’s copyright notice are included on the printed copy. Any other electronic reproduction or other printed versions is strictly prohibited.
The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.
Copyright 1989, 1996, 2003
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.
Symptoms of the following disorders can be similar to those of Meckel syndrome. Comparisons may be useful for a differential diagnosis:
Smith-Lemli-Opitz (SLO) syndrome (RSH syndrome) is a rare hereditary neurological disorder characterized multiple abnormalities that are present at birth (congenital). Symptoms may include characteristic facial features, mental retardation, extra fingers or toes (polydactyly), loss of vision, incomplete development of the male genitalia, short nose with displaced nostrils and a smaller than normal size opening of the stomach (pyloric stenosis). In some cases, heart abnormalities may be present. The specific symptoms associated with each case vary greatly. Smith-Lemli-Optiz syndrome is inherited as an autosomal recessive trait. (For more information on this disorder, choose "Smith-Lemli-Opitz" as your search term in the Rare Disease Database.)
Trisomy 13 Syndrome is a rare chromosomal disorder in which all or a portion of chromosome 13 appears three times (trisomy) rather than twice in cells of the body. In some affected individuals, only a percentage of cells may contain the extra 13th chromosome (mosaicism), whereas other cells contain the normal chromosomal pair. In individuals with Trisomy 13 syndrome, the range and severity of associated symptoms and findings may depend on the specific location of the duplicated (trisomic) portion of chromosome 1, as well as the percentage of cells containing the abnormality. However, in many affected infants and children, such abnormalities may include developmental delays, profound mental retardation, unusually small eyes (microphthalmia), an abnormal groove in the upper lip (cleft lip), incomplete closure of the roof of the mouth (cleft palate), undescended testes (cryptorchidism) in affected males, and extra (supernumerary) fingers and toes (polydactyly). Additional malformations of the head and facial (craniofacial) area may also be present, such as a relatively small head (microcephaly) with a sloping forehead; a broad, flat nose; widely set eyes (ocular hypertelorism); vertical skin folds covering the eyes; inner corners (epicanthal folds); scalp defects; and malformed, low-set ears. Affected infants may also have incomplete development of certain regions of the brain (e.g., the forebrain); kidney (renal) malformations; and structural heart (cardiac) defects at birth (congenital). Life-threatening complications may develop during infancy or early childhood. (For more information on this disorder, choose "Trisomy 13" as your search term in the Rare Disease Database.)
Short rib-polydactyly syndromes are a group of rare skeletal disorders characterized by growth deficiency resulting in short stature, abnormally short ribs, and extra fingers and toes (polydactyly). There is significant overlap in the symptoms associated with the various short rib-polydactyly syndromes. Additional findings may include polycystic kidneys, underdevelopment (hypoplasia) of the lungs, genitourinary abnormalities, central nervous system abnormalities, developmental delays, and cleft lip and cleft palate. The short rib-polydactyly syndromes include Saldino-Noonan, Majewski, Verma-Naumoff and Beemer-Langer syndromes. These disorders are inherited as an autosomal recessive trait.
The following disorders may be associated with Meckel syndrome as secondary characteristics. They are not necessary for a differential diagnosis:
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. Excessive amounts of fluid accumulate around the brain and cause abnormally high pressure within the skull, swelling of the head (congenital hydrocephalus), and neurological impairment. Motor delays and learning problems may also occur. (For more information on this disorder, choose "Dandy-Walker malformation" as your search term in the Rare Disease Database.)
Arnold-Chiari malformation (ACM) is a rare malformation of the brain that is present at birth (congenital). Abnormalities at the base of the brain most frequently involve the displacement of the rearmost part of the brain (cerebellum) through the opening in the back of the skull (foramen magnum). A part of the cerebellum enters into the space at which the spinal cord enters the skull. Thus, a part of the brain typically reaches the spinal canal (upper cervical area) and interferes with the flow of cerebral spinal fluid (CSF) to and from the brain. It is this constraint of the flow of CSF that causes most of the damage rather than the tissue compression. (For more information on this disorder, choose "Arnold-Chiari malformation" as your search term in the Rare Disease Database.)
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.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.
Pereira L, Donnenfeld AE. Meckel Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:221.
Jones KL, ed. Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co: 1997:184.
Behrman RE, ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:1680.
Gorlin RJ, et al., eds. Syndromes of the Head and Neck, 3rd ed. New York, NY: Oxford University Press; 1990:724-6.
Johnson CA, et al. Molecular pathology and genetics of congenital hepatorenal fibrocystic syndromes. J Med. Genet. 2003;40:311-9.
Morgan NV, et al. A novel locus for Meckel-Gruber syndrome, MKS3, maps to chromosome 8q24. Hum Genet. 2002;111:456-61.
Tanriverdi HA, et al. Meckel-Gruber syndrome: a first trimester diagnosis of a recurrent case. Eur J Ultrasound. 2002;15:69-72.
Cincinnati P, et al. Dandy-Walker anomaly in Meckel-Gruber syndrome. Clin Dysmorphol. 2000;9:35-8.
Kjaer KW, et al. Skeletal malformations in fetuses with Meckel syndrome. Am J Med Genet. 1999;84:469-75.
Paavola P, et al. High-resolution physical and genetic mapping of the critical region for Meckel syndrome and Mulibrey Nanism on chromosome 17q22-23. Genome Res. 1999;9:267-76.
Roume J, et al. A gene for Meckel syndrome maps to chromosome 11q13. Am J Med Genet. 1998;63:1095-101.
Salonen R, Paavola P. Meckel syndrome. J Med Genet. 1998;35:497-501.
Paavola P, et al. Clinical genetic heterogeneity in Meckel syndrome. Hum Genet. 1997;101:88-92.
Shanks J, et al. Skeletal abnormalities in Meckel syndrome. Pediatr Pathol Lab Med. 1997;17:625-30.
Paavola P, et al. The locus for Meckel syndrome with mulpitle congneital anomalies maps to chromosome 17q21-q24. Nat Genet. 1995;11:213-5.
Ahdab-Barmada M, Claassen D. A distinctive triad of malformations of the central nervous system in the Meckel-Gruber syndrome. J Neuropathol Exp Neurol. 1990;49:610-20.
Casamassima AC, et al. A new syndrome with features of the Smith-Lemli-Opitz and Meckel Gruber syndromes in a sibship with cerebellar defects. Am J Med Genet. 1987;26:321-36.
Heikinheimo M, et al. Studies on the elevated amniotic fluid SP 1 in Meckels's syndrome; modified glycosylation of SP1. Placenta. 1987;8:427-32.
Salonen R, et al. The Meckel syndrome: clinicopathological findings in 67 patients. Am J Med Genet. 1984;18:671-89.
Majewski F, et al. Are bowing of long tubular bones and preaxial polydactyol signs of the Meckel syndrome? Hum Genet. 1983;65:125-33.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:249000; Last Update:11/19/2002. Entry No:603194; Last Update:11/19/2002. Entry No:607361; Last Update:11/19/2002.
Carter SM. Meckel-Gruber Syndrome. eMedicine Journal. 2003;3:10pp.
Report last updated: 2008/04/12 00:00:00 GMT+0