This syndrome was originally described by Johann Friedrich Meckel, a German anatomist, in 1822 and the description was refined by Georg Benno Gruber, a German physician, in 1934, more than a century later. Hence the condition is sometimes called Meckel-Gruber syndrome today. It is a severe malformation syndrome, in most cases incompatible with life beyond the neonatal period in most cases.
Brain malformations (primarily an opening in the skull containing brain tissue, called an encephalocele), kidney cysts, and extra fingers and toes are considered to be the three most important diagnostic signs of this syndrome. The skull defect is present in 90% of infants, extra digits are noted in about 80%, and enlarged kidneys with cysts are nearly always present. Many infants also have hydrocephalus with extra fluid on the brain. The lungs are often underdeveloped and serious breathing problems are usually present at birth. Polydactyly (extra digits) may be seen on both hands and feet and are sometimes associated with fusion (webbing) of some of the fingers and toes. Malformations of the liver are also seen in most patients. Cleft palate and sometimes cleft lip is a common feature and associated with other facial anomalies such as a sloping forehead, low-set ears and a broad, flat nose. The eyes often appear close together. The genitalia are underdeveloped and sometimes appear ambiguous. Often the long bones of the arms and legs are shortened and bowed.
Not all infants have all of these features since Meckel syndrome consists of a group of disorders with a wide range of manifestations.
Ultrasound early in the second trimester of pregnancy can detect many of these malformations.
Meckel syndrome with all of its forms may result from mutations in at least 9 genes. These gene changes generally must be present in both copies of a specific gene which results in an autosomal recessive pattern of inheritance. Parents are generally free of disease but if each carries only one copy of the mutation they can expect that each of their children have a 25% chance of having a form of Meckel syndrome.
Because of the wide range of malformations in this multisystem disorder, the diagnosis is generally made by a team of specialists including pediatricians, neurologists, orthopedists, and ophthalmologists. No single diagnostic test is conclusive. The prognosis is poor for survival beyond infancy since there is no effective treatment for the lack of normal lung, kidney, and liver function, among other problems.