Norman-Roberts syndrome
Encyclopedia
Lissencephaly 2, more commonly called Norman-Roberts syndrome, is a rare form of lissencephaly
caused by a mutation in the reelin
gene. A small number of cases have been described. The syndrome was first reported by M. Norman and M. Roberts et al. in 1976.
Lack of reelin prevents normal layering of the cerebral cortex
and disrupts cognitive development. Patients have cerebellar hypoplasia
and suffer from congenital lymphedema
and hypotonia
. The disorder is also associated with myopia
, nystagmus and generalized seizures.
Norman-Roberts syndrome is one of two known disorders caused by a disruption of the reelin
-signaling pathway. The other is VLDLR-associated cerebellar hypoplasia
, which is caused by a mutation in the gene coding for one of the reelin receptors, VLDLR
.
Disruption of the RELN gene in human patients is analogous to the malfunctioning RELN gene in the reeler
mouse.
Lissencephaly
Lissencephaly, which literally means smooth brain, is a rare brain formation disorder caused by defective neuronal migration during the 12th to 24th weeks of gestation, resulting in a lack of development of brain folds and grooves . It is a form of cephalic disorder...
caused by a mutation in the reelin
Reelin
Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...
gene. A small number of cases have been described. The syndrome was first reported by M. Norman and M. Roberts et al. in 1976.
Lack of reelin prevents normal layering of the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
and disrupts cognitive development. Patients have cerebellar hypoplasia
Cerebellar hypoplasia
Cerebellar hypoplasia is a developmental disorder characterized by the incomplete or underdevelopment of the cerebellum. It may be genetic or occur sporadically. Cerebellar hypoplasia may be caused by thyroid abnormalities, environmental influences such as drugs and chemicals or viral infections or...
and suffer from congenital lymphedema
Congenital lymphedema
Congenital lymphedema is a blockage of fluid in the developing fetal lymphatic system. It is diagnosed by a nuchal scan. Presence of this condition is also associated with congenital heart defect....
and hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
. The disorder is also associated with myopia
Myopia
Myopia , "shortsightedness" ) is a refractive defect of the eye in which collimated light produces image focus in front of the retina under conditions of accommodation. In simpler terms, myopia is a condition of the eye where the light that comes in does not directly focus on the retina but in...
, nystagmus and generalized seizures.
Norman-Roberts syndrome is one of two known disorders caused by a disruption of the reelin
Reelin
Reelin is a large secreted extracellular matrix protein that helps regulate processes of neuronal migration and positioning in the developing brain by controlling cell–cell interactions. Besides this important role in early development, reelin continues to work in the adult brain. It modulates the...
-signaling pathway. The other is VLDLR-associated cerebellar hypoplasia
VLDLR-associated cerebellar hypoplasia
VLDLR-associated cerebellar hypoplasia is a rare autosomal recessive condition caused by a disruption of the VLDLR gene...
, which is caused by a mutation in the gene coding for one of the reelin receptors, VLDLR
VLDL receptor
The very-low-density-lipoprotein receptor is a lipoprotein receptor that shows considerable similarity to the low-density-lipoprotein receptor...
.
Disruption of the RELN gene in human patients is analogous to the malfunctioning RELN gene in the reeler
Reeler
A reeler is a mouse mutant, so named because of its characteristic "reeling" gait. This is caused by profound hypoplasia of the mouse's cerebellum, in which the normal cerebellar folia are missing. The mutation is autosomal and recessive....
mouse.