Meckel syndrome | |
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Other names | Meckel–Gruber syndrome, Gruber syndrome, Dysencephalia splanchnocystica |
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This condition is inherited in an autosomal recessive pattern, meaning two copies of the gene in each cell are altered. | |
Specialty | Medical genetics ![]() |
Meckel-Gruber syndrome is a rare, lethal, ciliopathic, genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations (occipital encephalocele), polydactyly (post axial), hepatic developmental defects, and pulmonary hypoplasia due to oligohydramnios.
Meckel–Gruber syndrome is named for Johann Meckel and Georg Gruber. [1] [2] [3]
Meckel–Gruber syndrome (MKS) is an autosomal recessive lethal malformation. Recently, two MKS genes, MKS1 and MKS3, have been identified. A study done recently has described the cellular, sub-cellular and functional characterization of the novel proteins, MKS1 and meckelin, encoded by these genes. [4] The malfunction of this protein production is mainly responsible for this lethal disorder.
Type | OMIM | Gene |
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MKS1 | 609883 | MKS1 |
MKS2 | 603194 | TMEM216 |
MKS3 | 607361 | TMEM67 |
MKS4 | 611134 | CEP290 |
MKS5 | 611561 | RPGRIP1L |
MKS6 | 612284 | CC2D2A |
MKS7 | 608002 | NPHP3 |
MKS8 | 613846 | TCTN2 |
MKS9 | 614144 | B9D1 |
MKS10 | 611951 | B9D2 |
Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying, phenotypically-observed disorders. Thus, Meckel–Gruber syndrome is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alström syndrome, and some forms of retinal degeneration. [5] The MKS1 gene has been identified as being associated with a ciliopathy. [6]
Dysplastic kidneys are prevalent in over 95% of all identified cases. When this occurs, microscopic cysts develop within the kidney and slowly destroy it, causing it to enlarge to 10 to 20 times its original size. The level of amniotic fluid within the womb may be significantly altered or remain normal, and a normal level of fluid should not be criteria for exclusion of diagnosis.[ citation needed ]
Occipital encephalocele is present in 60% to 80% of all cases, and post-axial polydactyly is present in 55% to 75% of the total number of identified cases. Bowing or shortening of the limbs are also common.[ citation needed ]
Finding at least two of the three phenotypic features of the classical triad, in the presence of normal karyotype, makes the diagnosis solid. Regular ultrasounds and pro-active prenatal care can usually detect symptoms early on in a pregnancy.[ citation needed ]
There is no cure to the disease. Treatment is symptomatic and to make the baby as comfortable as possible. [7]
The disease is lethal. Most infants that are not stillborn with Meckel syndrome die within hours to days of birth. [8] The longest survival time reported in medical literature is 28 months. [9]
While not precisely known, it is estimated that the general rate of incidence, according to Bergsma, [10] for Meckel syndrome is 0.02 per 10,000 births. According to another study done six years later, the incidence rate could vary from 0.07 to 0.7 per 10,000 births. [11]
This syndrome is a Finnish heritage disease. Its frequency is much higher in Finland, where the incidence is as high as 1.1 per 10,000 births. It is estimated that Meckel syndrome accounts for 5% of all neural tube defects there. [12]
The Leicestershire Perinatal Mortality Survey for the years 1976 to 1982 had found high incidences of Meckel syndrome in Gujarati Indian immigrants. [13]
A genetic disorder is a genetic problem caused by one or more abnormalities formed in the genome. Most genetic disorders are quite rare and affect one person in every several thousands or millions. The earliest known genetic condition in a hominid was in the fossil species Paranthropus robustus, with over a third of individuals displaying Amelogenesis imperfecta.
Joubert syndrome is a rare autosomal recessive genetic disorder that affects the cerebellum, an area of the brain that controls balance and coordination.
Anencephaly is the absence of a major portion of the brain, skull, and scalp that occurs during embryonic development. It is a cephalic disorder that results from a neural tube defect that occurs when the rostral (head) end of the neural tube fails to close, usually between the 23rd and 26th day following conception. Strictly speaking, the Greek term translates as "no in-head", but it is accepted that children born with this disorder usually only lack a telencephalon, the largest part of the brain consisting mainly of the cerebral hemispheres, including the neocortex, which is responsible for cognition. The remaining structure is usually covered only by a thin layer of membrane—skin, bone, meninges, etc. are all lacking. With very few exceptions, infants with this disorder do not survive longer than a few hours or possibly days after their birth.
Exencephaly, is a type of cephalic disorder wherein the brain is located outside of the skull. This condition is usually found in embryos as an early stage of anencephaly. As an exencephalic pregnancy progresses, the neural tissue gradually degenerates.
Primary ciliary dyskinesia (PCD), is a rare, ciliopathic, autosomal recessive genetic disorder that causes defects in the action of cilia lining the respiratory tract, fallopian tube, and flagellum of sperm cells. The phrase "immotile ciliary syndrome" is no longer favored as the cilia do have movement, but are merely inefficient or unsynchronized.
Ellis–van Creveld syndrome is a rare genetic disorder of the skeletal dysplasia type.
Bardet–Biedl syndrome (BBS) is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, hypogonadism, and kidney failure in some cases. Historically, slower mental processing has also been considered a principal symptom but is now not regarded as such.
Agenesis of the corpus callosum (ACC) is a rare birth defect in which there is a complete or partial absence of the corpus callosum. It occurs when the corpus callosum, the band of white matter connecting the two hemispheres in the brain, fails to develop normally, typically during pregnancy. The fibers that would otherwise form the corpus callosum become longitudinally oriented along the ipsilateral ventricular wall and form structures called Probst bundles.
Dandy–Walker syndrome (DWS) is a rare group of congenital human brain malformations. There are three subtypes which affect multiple organs to varying degrees, but the fundamental abnormalities involve the cerebellum which controls muscle coordination. The adjacent third and fourth ventricles are often affected, which can alter the flow of cerebrospinal fluid, increase intracranial pressure and lead to multiple other brain function problems.
Alström syndrome (AS), also called Alström–Hallgren syndrome, is a very rare autosomal recessive genetic disorder characterised by childhood obesity and multiple organ dysfunction. Symptoms include early-onset type 2 diabetes, cone-rod dystrophy resulting in blindness, sensorineural hearing loss and dilated cardiomyopathy. Endocrine disorders typically also occur, such as hypergonadotrophic hypogonadism and hypothyroidism, as well as acanthosis nigricans resulting from hyperinsulinemia. Developmental delay is seen in almost half of people with Alström syndrome.
Nephronophthisis is a genetic disorder of the kidneys which affects children. It is classified as a medullary cystic kidney disease. The disorder is inherited in an autosomal recessive fashion and, although rare, is the most common genetic cause of childhood kidney failure. It is a form of ciliopathy. Its incidence has been estimated to be 0.9 cases per million people in the United States, and 1 in 50,000 births in Canada.
Senior–Løken syndrome is a congenital eye disorder, first characterized in 1961. It is a rare, ciliopathic, autosomal recessive disorder characterized by juvenile nephronophthis and progressive eye disease.
A ciliopathy is a genetic disorder of the cellular cilia or the cilia anchoring structures, the basal bodies, or of ciliary function.
Marden–Walker syndrome (MWS) is a rare autosomal recessive congenital disorder. It is characterized by blepharophimosis, microcephaly, micrognathia, multiple joint contractures, arachnodactyly, camptodactyly, kyphoscoliosis, and delayed motor development and is often associated with cystic dysplastic kidneys, dextrocardia, Dandy-Walker malformation, and agenesis of corpus callosum".
Orofaciodigital syndrome 1 (OFD1), also called Papillon-League and Psaume syndrome, is an X-linked congenital disorder characterized by malformations of the face, oral cavity, and digits with polycystic kidney disease and variable involvement of the central nervous system.
Hydrolethalus syndrome (HLS) is a rare genetic disorder that causes improper fetal development, resulting in birth defects and, most commonly, stillbirth.
Meckel syndrome, type 1 also known as MKS1 is a protein that in humans is encoded by the MKS1 gene.
A Finnish heritage disease is a genetic disease or disorder that is significantly more common in people whose ancestors were ethnic Finns, natives of Finland and Sweden (Meänmaa) and Russia. 36 rare diseases are regarded as Finnish heritage diseases. The diseases are not restricted to Finns; they are genetic diseases with far wider distribution in the world, but due to founder effects and genetic isolation they are more common in Finns.
McKusick–Kaufman syndrome is a genetic condition associated with MKKS.
Ciliogenesis is defined as the building of the cell's antenna or extracellular fluid mediation mechanism. It includes the assembly and disassembly of the cilia during the cell cycle. Cilia are important organelles of cells and are involved in numerous activities such as cell signaling, processing developmental signals, and directing the flow of fluids such as mucus over and around cells. Due to the importance of these cell processes, defects in ciliogenesis can lead to numerous human diseases related to non-functioning cilia. Ciliogenesis may also play a role in the development of left/right handedness in humans.
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