Tropism
The term viral tropism refers to the cell types a virus infects. HIV can infect a variety of immune cells such as CD4+ T cells, macrophages, and microglial cells. HIV-1 entry to macrophages and CD4+ T cells is mediated through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells membrane and also with chemokine co-receptors.Macrophage-tropic (M-tropic) strains of HIV-1, or non-syncytia-inducing strains (NSI; now called R5 viruses) use the β-chemokine receptor, CCR5, for entry and are thus able to replicate in both macrophages and CD4+ T cells. This CCR5 co-receptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype. Indeed, macrophages play a key role in several critical aspects of HIV infection. They appear to be the first cells infected by HIV and perhaps the source of HIV production when CD4+ cells become depleted in the patient. Macrophages and microglial cells are the cells infected by HIV in the central nervous system. In the tonsils and adenoids of HIV-infected patients, macrophages fuse into multinucleated giant cells that produce huge amounts of virus. T-tropic strains of HIV-1, or syncytia-inducing strains (SI; now called X4 viruses) replicate in primary CD4+ T cells as well as in macrophages and use the α-chemokine receptor, CXCR4, for entry.Dual-tropic HIV-1 strains are thought to be transitional strains of HIV-1 and thus are able to use both CCR5 and CXCR4 as co-receptors for viral entry. The α-chemokine SDF-1, a ligand for CXCR4, suppresses replication of T-tropic HIV-1 isolates.
In microlissencephaly cases, the primary sulci would be unusually wide and flat while secondary sulci would be missing.At birth, lissencephaly with a head circumference of less than minus three standard deviations (< –3 SD) is considered microlissencephaly.Although genetic diagnosis in patients with MLIS is challenging, exome sequencing has been suggested to be a powerful diagnostic tool. Dobyns-Barkovich classification
In 1999, Dobyns and Barkovich suggested a classification of patients with severe microcephaly combined with gyral abnormalities including: microcephaly with simplified gyral pattern (MSGP), microlissencephaly and polymicrogyria. The classification divided those patients into ten groups in which MSGP represented the first four groups, microlissencephaly referred to the groups from 5-8 and polymicrogyria in the last two groups.In Dobyns-Barkovich classification, Dobyns-Barkovich type 6 is equivalent to Norman-Roberts syndrome (MLIS1) while Dobyns-Barkovich type 8 corresponds to Barth microlissencephaly syndrome (MLIS2). Differential diagnosis
Microlissencephaly is considered a more severe form than microcephaly with simplified gyral pattern. Microlissencephaly is characterized by a smooth cortical surface (absent sulci and gyri) with a thickened cortex (> 3 mm) and is usually associated with other congenital anomalies. Microcephaly with a simplified gyral pattern has too few sulci and normal cortical thickness (3 mm) and is usually an isolated anomaly. Prognosis
Many patients will die within the first year of life. Epidemiology
Microlissencephaly is listed in Orphanet database as a rare disease. There is not much information available about the epidemiology of microlissencepahly in literature.