A third type of lissencephaly that does not fufil diagnostic criteria of type I ("classical") and type II ("cobblestone") lissencephaly was described in 1996 as a new entity identified as MIM.601160. Autosomal recessive inheritance.

This lethal familial syndrome comprises micrencephaly/lissencephaly and a spectrum of abnormalities lined to a severe fetal akinesia deformation sequence. Neuropathological findings suggest severe neurodegeneration leading to a marked neuronal dropout of the entire central nervous system and atrophy.

Similar neuropathological findings have been described in the Neu-Laxova syndrome (NLS), an apparently different lethal malformation syndrome.

Neuropathological similarities between MIM.601160 and NLS raise the question of clinicopathological variability and genetic heterogeneity of type III lissencephaly.

Synopsis

 primary central nervous system degeneration
 fetal akinesia sequence (FAS)

• severe arthrogryposis

 cerebral malformations
 corpus callosum agenesis
 vermis agenesis

 pulmonary hypoplasia
 polyhydramnios

 cerebrospinal anomalies

• smooth brain (lissencephaly)
• hypoplastic brain stem
• cystic cerebellum
• large ventricles
• bilateral multicystic periventricular lesions extending to the basal ganglia
• severe neuronal loss
• agyric brain
• hypoplastic brain stem
• hypoplastic cerebellum
• severe neuronal loss of the cortical plate, matrix zone, basal ganglia, brainstem nuclei and spinal cord
• axonal swelling
• microcalcification

 skeletal anomalies

• epiphyseal stippling of cervical vertebrae, feet and sacrum
• shortened metacarpal bones with hypoplastic distal phalanges
• epiphyseal calcifications
• metacarpophalangeal bone dysplasia

Copyright Wiley-Liss. Inc.

See also

 lissencephalies

References

 Attia-Sobol, J.; Encha-Razavi, F.; Hermier, M.; Vitrey, D.; Verloes, A.; Plauchu, H. : Lissencephaly type III, stippled epiphyses and loose, thick skin: a new recessively inherited syndrome. Am. J. Med. Genet. 99: 14-20, 2001. PubMed ID : #11170088#

 Encha Razavi, F.; Larroche, J. C.; Roume, J.; Gonzales, M.; Kondo, H. C.; Mulliez, N. : Lethal familial fetal akinesia sequence (FAS) with distinct neuropathological pattern: type III lissencephaly syndrome. Am. J. Med. Genet. 62: 16-22, 1996. PubMed ID : #8779318#