Meckel-Gruber syndrome is a rare, lethal

ciliopathic A ciliopathy is any genetic disorder that affects the cellular cilia or the cilia anchoring structures, the basal bodies, or ciliary function. Primary cilia are important in guiding the process of development, so abnormal ciliary function while ...

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

, characterized by renal cystic dysplasia,

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

malformations (occipital encephalocele),

polydactyly Polydactyly or polydactylism (), also known as hyperdactyly, is an anomaly in humans and animals resulting in supernumerary fingers and/or toes. Polydactyly is the opposite of oligodactyly (fewer fingers or toes). Signs and symptoms In humans ...

(postaxial),

hepatic The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

developmental defects, and

pulmonary hypoplasia Pulmonary hypoplasia is incomplete development of the lungs, resulting in an abnormally low number or size of bronchopulmonary segments or alveoli. A congenital malformation, it most often occurs secondary to other fetal abnormalities that inter ...

due to

oligohydramnios Oligohydramnios is a medical condition in pregnancy characterized by a deficiency of amniotic fluid, the fluid that surrounds the fetus in the abdomen, in the amniotic sac. It is typically diagnosed by ultrasound when the amniotic fluid index (A ...

. Meckel–Gruber syndrome is named for

Johann Meckel Johann Friedrich Meckel (17 October 1781 – 31 October 1833), often referred to as Johann Friedrich Meckel, the Younger, was a German anatomist born in Halle, Saxony-Anhalt, Halle. He worked as a professor of anatomy, pathology and zoology at the ...

and Georg Gruber.

Pathophysiology

Meckel–Gruber syndrome (MKS) is an autosomal recessive lethal malformation. Recently, two MKS

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

MKS1 Meckel syndrome, type 1 also known as MKS1 is a protein that in humans is encoded by the ''MKS1'' gene. Function The MKS1 protein along with meckelin are part of the flagellar apparatus basal body proteome and are required for cilium formati ...

and MKS3, have been identified. A study done recently has described the

cellular Cellular may refer to: *Cellular automaton, a model in discrete mathematics * Cell biology, the evaluation of cells work and more * ''Cellular'' (film), a 2004 movie *Cellular frequencies, assigned to networks operating in cellular RF bands *Cell ...

sub-cellular The cell is the basic structural and functional unit of life forms. Every cell consists of a cytoplasm enclosed within a membrane, and contains many biomolecules such as proteins, DNA and RNA, as well as many small molecules of nutrients and ...

and functional characterization of the novel

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

and meckelin, encoded by these genes. The malfunction of this protein production is mainly responsible for this lethal disorder.

Relation to other rare genetic disorders

Recent findings in genetic research have suggested that a large number of

s, both

genetic syndromes A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired ...

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 In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

-observed disorders. Thus, Meckel–Gruber syndrome is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia,

Bardet–Biedl syndrome Bardet–Biedl syndrome (BBS) is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized by rod/cone dystrophy, polydactyly, central obesity, hypogonadism, and kidney dysfunction in som ...

polycystic kidney Polycystic kidney disease (PKD or PCKD, also known as polycystic kidney syndrome) is a genetic disorder in which the renal tubules become structurally abnormal, resulting in the development and growth of multiple cysts within the kidney. These cy ...

and liver disease,

nephronophthisis 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 o ...

Alström syndrome 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 dystr ...

, and some forms of retinal degeneration. The MKS1 gene has been identified as being associated with a ciliopathy.

Diagnosis

Dysplastic kidneys are

prevalent In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...

in over 95% of all identified cases. When this occurs,

microscopic The microscopic scale () is the scale of objects and events smaller than those that can easily be seen by the naked eye, requiring a lens (optics), lens or microscope to see them clearly. In physics, the microscopic scale is sometimes regarded a ...

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 The amniotic fluid is the protective liquid contained by the amniotic sac of a gravid amniote. This fluid serves as a cushion for the growing fetus, but also serves to facilitate the exchange of nutrients, water, and biochemical products betwee ...

within the womb may be significantly altered or remain normal, and a normal level of fluid should not be criteria for exclusion of diagnosis.

Occipital The occipital bone () is a cranial dermal bone and the main bone of the occiput (back and lower part of the skull). It is trapezoidal in shape and curved on itself like a shallow dish. The occipital bone overlies the occipital lobes of the cereb ...

encephalocele Encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. These defects are caused by failure of the neural tube to close completely during fetal develop ...

is present in 60% to 80% of all cases, and post-axial

is present in 55% to 75% of the total number of identified cases.

Bowing Bowing (also called stooping) is the act of lowering the torso and head as a social gesture in direction to another person or symbol. It is most prominent in Asian cultures but it is also typical of nobility and aristocracy in many European coun ...

or shortening of the limbs are also common. Finding at least two of the three phenotypic features of the classical triad, in the presence of normal

karyotype A karyotype is the general appearance of the complete set of metaphase chromosomes in the cells of a species or in an individual organism, mainly including their sizes, numbers, and shapes. Karyotyping is the process by which a karyotype is disce ...

, makes the diagnosis solid. Regular

ultrasound Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...

s and pro-active prenatal care can usually detect

symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

s early on in a

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

Management

There is no cure to the disease. Treatment is symptomatic and to make the baby as comfortable as possible.

Prognosis

The disease is lethal. Most infants that are not stillborn with Meckel syndrome die within hours to days of birth. The longest survival time reported in medical literature is 28 months.

Incidence

While not precisely known, it is estimated that the general rate of incidence, according to Bergsma, 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. This syndrome is a

Finnish heritage disease 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 ( Karelia and Ingria). There are 36 rare diseases regar ...

. Its frequency is much higher in

Finland Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of B ...

, 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. The

Leicestershire Leicestershire ( ; postal abbreviation Leics.) is a ceremonial and non-metropolitan county in the East Midlands, England. The county borders Nottinghamshire to the north, Lincolnshire to the north-east, Rutland to the east, Northamptonshire t ...

Perinatal Mortality Survey for the years 1976 to 1982 had found high incidences of Meckel syndrome in

Gujarati Gujarati may refer to: * something of, from, or related to Gujarat, a state of India * Gujarati people, the major ethnic group of Gujarat * Gujarati language, the Indo-Aryan language spoken by them * Gujarati languages, the Western Indo-Aryan sub- ...

Indian immigrants.

References

External links

{{DEFAULTSORT:Meckel-Gruber syndrome Autosomal recessive disorders Ciliopathy Congenital disorders of nervous system Congenital disorders of digestive system Congenital disorders of urinary system Rare syndromes