LIS1 knockout homozygous null mice die during embryogenesis and heterozygous mice survive with delayed neuronal migration confirmed by in vitro and in vivo cell migration assays. Most lissencephaly cases are associated with deletions of mutations of the LIS1 gene and the results are usually more severe in the posterior brain regions.One study showed that of an isolated group of patients with lissencephaly, 40% resulted from an LIS1 deletion and another 25% resulted from an intragenic mutation of the gene. Patients with missense mutations tend to have less severe symptoms, pachygyria, and rare cases of subcortical band heterotopia. Truncated (shortened) mutations of LIS1 tend to cause severe lissencephaly. Doublecortin
Doublecortin (DCX or XLIS) mutations are responsible for X-linked disorders. While LIS1 mutations tend to cause severe malformations in the posterior brain, DCX mutations focus much of their destruction on anterior malformations and are linked to lissencephaly in males and subcortical band heterotopias in females. Women with DCX mutations tend to have an anteriorly-predominant subcortical band heterotopia and pachygyria. DCX was the first known gene causing X-linked lissencephaly and subcortical band heterotopia. It is found on chromosome Xq22.3-q23 and has nine exons that code for 360 proteins. DCX is expressed exclusively in the fetal brain.Spastic cerebral palsy is by far the most common type, occurring in 70% to 80% of all cases. Moreover, spastic CP accompanies one of the other types in 30% of all cases.
In 2011, an international consensus group adopted a definition of cachexia as "a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that can be partially but not entirely reversed by conventional nutritional support. "Cachexia differs from weight loss due to malnutrition from malabsorption, anorexia nervosa, or anorexia due to major depressive disorder. Weight loss from inadequate caloric intake generally causes fat loss before muscle loss, whereas cachexia causes predominantly muscle wasting. Cachexia is also distinct from sarcopenia, or age-related muscle loss, although they often co-exist. Treatment
The management of cachexia depends on the underlying cause, the general prognosis, and the needs of the person affected. The most effective approach to cachexia is treating the underlying disease process. An example is the reduction in cachexia from AIDS by highly active antiretroviral therapy. However this is often not possible or maybe inadequate to reverse the cachexia syndrome in other diseases. Approaches to mitigate muscle loss include exercise, nutritional therapies, and medications. Exercise
Therapy that includes regular physical exercise can be recommended for the treatment of cachexia due to the positive effects of exercise on skeletal muscle but current evidence remains uncertain as to its effectiveness, acceptability and safety for cancer patients. Individuals with cachexia generally report low levels of physical activity and few engage in an exercise routine, owing to low motivation to exercise and a belief that exercising may worsen their symptoms or cause harm.