Significant increases in aquaporin-4 expression that occur over the course of animal aging, together with a reduced cerebrospinal fluid outflow rate and ventricular compliance, contribute to produce more severe hydrocephalus related to hypoxic events in aged mice, with a notable impairment in cognitive function.
In a state of aquaporin-4 dysfunction such as in neuromyelitis optica, altered cerebrospinal fluid resorption could lead to acute hydrocephalus by a nonobstructive mechanism.
Described disorders caused by mutations in the ARX gene include: hydrocephaly with abnormal genitalia (HYD-AG), lissencephaly with abnormal genitalia (XLAG), agenesis of corpus callosum with abnormal genitalia (ACC-AG), Partington syndrome (PRTS), X-linked infantile spasms (ISSX), myoclonic epilepsy with spasticity and mental retardation (XMESID), and nonspecific mental retardation (NS-XLMR).
Therefore, we propose here to refer to this clinical syndrome with the acronym CRASH, for Corpus callosum hypoplasia, Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus.
In the neonatal population, it is typically associated with an excess of antidiuretic hormone and rarely has been found to be associated with hydrocephalus, short of being caused by the subsequent treatment of hydrocephalus.
The nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* was identical to a B3GALNT2 mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus.
We provide strong genetic and biochemical evidence that hydrocephaly and white spotting in B3glct mutants resulted from loss of ADAMTS20, eye abnormalities from partial reduction of ADAMTS9, and cleft palate from loss of ADAMTS20 and partially reduced ADAMTS9 function.