Meckel syndrome is a very severe condition characterized by numerous kidney cysts, protrusion of a portion of the brain through a skull opening (occipital encephalocele), and extra fingers or toes (polydactyl).


Meckel syndrome is inherited as an autosomal genetic condition which is recessive. Recessive genetic abnormalities arise when each parent inherits the same anomalous gene for the same phenotype. When an individual receives one normal gene for the disease and one altered gene, the person will be a carrier for the disease, but will not display any symptoms. The chance of both carrier parents transmitting the altered gene and thus having an affected child with each pregnancy is 25 per cent. The chance with each pregnancy of having a child who is a carrier like the parents is 50 per cent. The probability of both parents receiving normal genes for a child is 25%.

Meckel syndrome can be caused by mutations in thirteen genes: B9D1, B9D2, CC2D2A, CEP290, MKS1, RPGRIP1L, TCTN2, TCTN3, TMEM67, TMEM107, TMEM216, TMEM231 and TMEM237. Mutations in these 13 genes account for 75% of all cases; the remaining 25% have unknown genetic causes. Most of these genes are also responsible for a neurological disorder called Joubert syndrome, leading to the concept that Meckel syndrome is the extreme lethal form of Joubert syndrome.

The proteins formed by these genes, called primary cilia are known to influence cell structures. Cilia are microscopic projections that stick out on the cell’s surface and help relay information across signalling routes. Cilia is essential for cell structure and function, particularly in the kidney, liver and the brain cells. Mutations can cause problems in cell function due to chemical signalling problems between cells. Deficient cilia, particularly in the kidneys and brain may be responsible for developmental abnormalities.


The most common central nervous system abnormality associated with Meckel’s syndrome is occipital encephalocele, a disorder in which an infant is born with a gap in the skull (i.e., not sealing part of one or more of the plates that form the skull). Through this distance, the membranes that cover the brain (meninges) and brain tissue frequently protrude. Accumulation of excessive cerebrospinal fluid (CSF) in the skull can result in occipital encephalocele, which causes pressure on the brain tissues (hydrocephalus).

Additional central nervous system defects that can occur in infants with Meckel syndrome include the absence of a large portion of the brain, neck, and scalp (anencephaly), Dandy-Walker malformation, and a disorder known as microcephaly, in which the head size is smaller than expected for age and sex.

Individuals affected can also have extra fingers and toes, most commonly additional digits on the “pinky” side of the hands (postaxial polydactyl). Additional skeletal malformations include bowing of the long bones of the arms and legs, the curvature of the fifth fingers (clinodactyly), webbing of the fingers and toes (syndactyly), and club foot (talipes equinovarus), where the foot is rotated internally.

In some individuals, genitourinary tract defects may occur, including failure of one or both of
the testes to descend into the scrotum (cryptorchidism), underdeveloped (hypoplastic) bladder, and incomplete genital growth.

Some infants affected may have anomalies that affect other body organs like the liver, lungs or heart. With multiple cysts and excessive fibrous tissue (fibrosis), the liver can get abnormally swollen (hepatomegaly). There may also be widening (dilatation) and fibrosis of the passages which carry bile from the liver to the small intestines (bile ducts). The lungs may be underdeveloped (hypoplastic) and maybe cleft (cleft epiglottis) to the structure that protects larynx entry while swallowing. Abnormally the spleen can be swollen (splenomegaly) or absent (asplenia).

Anomalies in the heart can include septal atrial and ventricular defects (ASDs and VSDs) and patent ductus arteriosus. ASDs are distinguished by an irregular opening in the fibrous partition (septum) separating the heart from the two upper chambers (atria). VSDs are distinguished by an irregular septum opening, which separates two lower chambers (ventricles) of the heart. The extent of the symptoms is determined by the scale, position, and the existence of a septal defect and any related abnormalities. Patent ductus arteriosus is a condition in which the passage (duct) between the blood vessel leading into the lungs (pulmonary artery) and the body’s main artery (aorta) does not close after birth.


Diagnosis of the occipital encephalocele and dysplastic kidneys can be made on fetal ultrasonography. For diagnosis of MKS, two of the three major malformations or two other anomalies together with one classical function are necessary. An autopsy can be appropriate, too. The condition is observed mostly before the week of the 14thgestation. The diagnosis can be confirmed by molecular genetic testing to direct genetic counselling.


Differential diagnoses include trisomy 13, Bardet-Biedl syndrome, Hydrolethalus, and Smith-Lemli-Opitz Syndrome.


Prenatal diagnosis by ultrasonography is possible starting from 12 weeks of pregnancy. Encephalocele, cystic kidneys and polydactyly may be detected.


No treatment is currently available for Meckel syndrome which has a constantly fatal outcome.

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