MECKEL-GRUBER SYNDROME
DEFINITION:
An autosomal recessive disorder of unknown etiology characterized
by an occipital encephalocele, cystic dysplastic kidneys, and
polydactyly.
EPIDEMIOLOGY:
- incidence: over 200 cases reported
- age of onset:
- prenatally by ultrasound or at birth
- risk factors:
- familial - autosomal recessive
- chrom.#: 17q21-q24
- gene: ?
- M = F
- prevalent in Finland (1:9000 births), and among the Tatars
and the Gujarati Indians
PATHOGENESIS:
- also called Meckel Syndrome, Gruber Syndrome, Dysencephalia
Splanchnocytica
- originally described by J.R. Meckel in 1822 and later by G.B.
Gruber in 1934 who called the condition Dysencephalia
Splanchnocytica
2. Pathogenesis
CLINICAL FEATURES:
- occipital encephalocele
- anencephaly, microcephaly, or hydrocephaly +/- Arnold-Chiari
Malformation
- cerebral and cerebellar hypoplasia
- absent olfactory lobes and tract, corpus callosum, and
septum pallucidum
2. Facial Manifestations
- broad, round face
- low, sloping forehead
- eyes:
- hypo- or hypertelorism, upslanting palpebral fissures,
microphthalmia, coloboma of the iris, cataracts
- broad, flattened nose
- broad cheeks
- low set ears
- hypoplastic or absent philtrum and/or nasal septum
- mouth:
- wide, full lips, cleft palate +/- cleft lip, natal teeth,
buccal frenula, small lobulated or cleft tongue
- micrognathia
- short, webbed neck
- Potter-like facies with severe oligohydramnios
3. Renal Manifestations
- bilateral cystic dysplasia with grossly enlarged kidneys
- absent, hypoplastic, or duplicated ureters
- absent or hypoplastic bladder
- urethra absent or not connected to the bladder
4. Limb Malformations
- postaxial polydactyly usually bilateral involving both hands
and feet
- partial or total syndactyly of the fingers and toes
- clinodactyly
- ulnar deviation of the hands
- clubfeet
- short, bowed limbs
5. Genital Manifestations
- ambiguous genitalia
- absent ovaries or testes (cryptorchidism)
6. Cardiac Manifestations
- septal defects (ASD, VSD)
- Patent Ductus Arteriosus
- Coarctation of the Aorta
- Pulmonary Stenosis
7. Gastrointestinal Manifestations
- hepatomegaly with microscopic cysts and fibrosis
- absent gall bladder
- dilated bile ducts
2. Spleen
- absent, accessory, or splenomegaly
3. Adrenals
4. Others
- omphalocele
- intestinal malrotation
- imperforate anus
8. Respiratory Manifestations
INVESTIGATIONS:
- occipital encephalocele or cystic dysplastic kidneys
detected by ultrasound as early as midtrimester
- elevated maternal and amniotic fluid alpha fetoprotein (with
encephalocele or anencephaly)
MANAGEMENT:
- most cases are stillborn or die within a few days to weeks
of delivery
- oldest known survivor died at 4 months of age
- genetic counselling
ADDITIONAL REFERENCES:
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