57 Meckel Syndrome
Meckel-Gruber syndrome, dysencephalia splanchnocystica
Microcephaly, posterior encephalocele, microphthal- mia, congenital heart defects, cleft palate, postaxial polydactyly, polycystic kidneys
Frequency: 1 in 9,000 live births in Finland, 1 in 15,000–50,000 elsewhere.
Genetics
Autosomal recessive (OMIM 249000); one locus maps to 17q22q23, a second locus to 11q13, a third locus at 8q24.
Clinical Features
• Oligohydramnios (60%), fetal distress, perinatal death
• Sloping forehead, microcephaly, posterior ence- phalocele
• Potter-like facies
• Hypertelorism, upward slanting palpebral fis- sures, microphthalmia, anophthalmia, cataracts, coloboma
• Wide mouth, neonatal teeth, small, lobulated, cleft tongue, cleft lip and palate
• Micrognathia
• Short neck
• Postaxial hand and foot polydactyly, syndactyly, clubfeet
• Cryptorchidism, hypoplastic phallus, hypospadias
• Polycystic kidneys, urogenital malformations
• Heart defects
• Pulmonary hypoplasia
• Hepatic fibrosis, macroscopic liver cysts, spleen anomalies, pancreatic fibrosis
• CNS anomalies (anencephaly (60%), absent olfac- tory bulbs (80%), hydrocephalus, Dandy-Walker malformation, cerebral and cerebellar aplasia/hy- poplasia, polymicrogyria, heterotopias, holopros- encephaly, agenesis of corpus callosum, etc.)
Differential Diagnosis
• Neural tube defects
• Hydrolethalus
• Trisomy 13
Radiographic Features Skull
• Occipital defect with encephalocele
• Microcephaly with small, sloping forehead
• Micrognathia Limbs
• Postaxial polydactyly of hands (55-80%) and feet, syndactyly, clinodactyly
• Short limbs, angulated tibias
• Clubfoot Chest
• Small thorax with hypoplastic lungs
• Clavicles with lateral hooks
Bibliography
Blankenberg TA, Ruebner BH, Ellis WG, Bernstein J, Dimmick JE. Pathology of renal and hepatic anomalies in Meckel syndrome. Am J Med Genet Suppl 1987; 3: 395–410 Canepa G, Maroteaux P, Pietrogrande V. Sindromi dismorfiche
e malattie costituzionali dello scheletro. Piccin, Padova, 1996
Fraser FC, Lytwyn A. Spectrum of anomalies in the Meckel syndrome or: “Maybe there is a malformation syndrome with at least one constant anomaly.” Am J Med Genet 1981;
9: 67–73
Kjaer KW, Fischer Hansen B, Keeling JW, Kjaer I. Skeletal mal- formations in fetuses with Meckel syndrome. Am J Med Genet 1999; 84: 469–75
Opitz JM, Howe JJ. The Meckel syndrome (dysencephalia splanchnocystica, the Gruber syndrome). Birth Defects Orig Art Ser 1969; 5: 167–79
Paavola P, Salonen R, Weissenbach J, Peltonen L. The locus for Meckel syndrome with multiple congenital anomalies maps to chromosome 17q21-q24. Nat Genet 1995; 11: 213–5 Rapola J, Salonen R. Visceral anomalies in the Meckel syn-
drome. Teratology 1985; 31: 193–201
Roume J, Genin E, Cormier-Daire V, Ma HW, Mehaye B, Attie T, Razavi-Encha F, Fallet-Bianco C, Buenerd A, Clerget-Dar- poux F, Munnich A, Le Merrer M. A gene for Meckel syn- drome maps to chromosome 11q13. Am J Hum Genet 1998;
63: 1095–101
Shanks J, Kerr B, Russell SA, Kingston H, Moore L. Skeletal ab- normalities in Meckel syndrome. Pediatr Pathol Lab Med 1997; 17: 625–30
Salonen R. The Meckel syndrome: clinicopathological findings in 67 patients. Am J Med Genet 1984; 18: 671–89
Salonen R, Paavola P. Meckel syndrome. J Med Genet 1998; 35:
497–501
Wright C, Healicon R, English C, Burn J. Meckel syndrome:
what are the minimum diagnostic criteria? J Med Genet 1994; 31: 482–5
Meckel Syndrome 748
Meckel Syndrome 749
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Fig. 57.1. Patient 1, newborn. Note microcephaly with sloping forehead, posterior encephalocele, Potter-like facies, abnormal ears, and postaxial polydactyly
Fig. 57.2. Patient 2, newborn. There is microcephaly with characteris- tic sloping forehead, a large occip- ital encephalocele, and flat face, with malar and mandibular hy- poplasia. (Reprinted, with permis- sion, from Canepa et al. 1996)
Fig. 57.3. Patient 2, newborn. Postaxial polydactyly. (Reprint- ed, with permission, from Canepa et al. 1996)
