Meckel-Gruber Syndrome (MKS)

At a glance

It is characterized by postaxial polydactyly and central nervous system malformation (encephalocele, severe hydrocephalus), large polycystic kidneys, and liver failure (fibrosis). Other clinical features include microcephaly, abnormality of the larynx and tongue, severe mandibular micrognathism, obesity, and cleft lip/palate. Associated abnormalities include oligohydramnios, oral clefting, and genital anomalies. Pulmonary hypoplasia is the leading cause of death.

Synonyms

Meckel Syndrome; Gruber Syndrome; Dysencephalia Splanchnocystica; MKS.

History

This medical condition was first described in 1822 by Johann F. Meckel (1781-1833), a German anatomist, and subsequently clinically expanded by Georg Gruber (1884-1977) in 1934. Gruber published reports on individuals with Meckel Syndrome and named the disorder Dysencephalia Splanchnocystica.

Nature

Genetic disorder characterized mainly by occipital encephalocele (90%), polydactyly, and polycystic kidneys (75%), but with a wide phenotypic variation.

Incidence

Worldwide incidence of Meckel-Gruber Syndrome varies between 1:13,250 and 140,000 live births in general population. There is a predilection for the Finnish population, in whom the birth incidence is 1:9,000. It is estimated that Meckel Syndrome accounts for 5% of all neural tube defects in Finland. The incidence is reported in the Belgian Ancestry to be 1:3,000 people. In the Gujarati Indians, the prevalence was estimated at 1:1,300. It often occurs in the context of consanguineous unions. More than 200 cases have been described in the literature.

Genetic inheritance

Autosomal recessive; a gene has been identified on chromosome 17q21-q24.

Pathophysiology

It has been suggested that a failure of mesodermal induction causes MKS. The induction cascades of early morphogenesis involve numerous growth factors, homeobox genes, and paired domain genes.

Diagnosis

Some authors consider that the minimal diagnostic criteria for the syndrome consist of cystic dysplasia of the kidney, fibrotic changes of the liver, and occipital encephalocele. Thus histologic studies are needed to confirm the diagnosis. Clinical features are highly variable among patients.

Clinical aspects

The main features are central nervous system malformations consisting usually of occipital encephalocele (with holoprosencephaly, agenesis of corpus callosum and/or hydrocephalus); seizures; postaxial polydactyly always involving the hand and occasionally the feet and polycystic kidneys; other urologic anomalies include either absent or hypoplastic ureters or bladder. Often the liver shows cystic changes with duct proliferation and fibrosis. Other anomalies include microcephaly, microphthalmia or anophthalmia, cleft lip and/or palate, genital anomalies, lung hypoplasia, and congenital heart disease such as atrial septal defect (ASD), ventricular septal defect (VSD), coarctation of the aorta, and patent ductus arteriosus (PDA). Patients also present a typical “Meckel appearance” with micrognathia, flat nose, hypertelorism, a sloping forehead, wide mouth with full lips, low-set ears, and short neck.

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