MedGen

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures (resulting from radiologically demonstrable polycystic osseous lesions), frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. The clinical course of PLOSL can be divided into four stages: 1. The latent stage is characterized by normal early development. 2. The osseous stage (3rd decade of life) is characterized by pain and tenderness, mostly in ankles and feet, usually following strain or injury. Fractures are typically diagnosed several years later, most commonly in the bones of the extremities. 3. In the early neurologic stage (4th decade of life), a change of personality begins to develop insidiously. Affected individuals show a frontal lobe syndrome (loss of judgment, euphoria, loss of social inhibitions, disturbance of concentration, and lack of insight, libido, and motor persistence) leading to serious social problems. 4. The late neurologic stage is characterized by progressive dementia and loss of mobility. Death usually occurs before age 50 years. [from GeneReviews]

Degenerative changes of the fat tissue. [from HPO]

A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior. [from HPO]

Schizophrenia is highly heritable, as shown by family, twin, and adoption studies. For example, for identical twins, if one twin develops schizophrenia, the other twin has about a 50% chance of also developing the disease. The risk of the general population developing the schizophrenia is about 0.3-0.7% worldwide. The search for “schizophrenia genes” has been elusive. Initial linkage studies looked at parts of the genome associated with schizophrenia, and many candidate genes were identified, including APOE, COMT, DAO, DRD1, DRD2, DRD4, DTNBP1, GABRB2, GRIN2B, HP, IL1B, MTHFR, PLXNA2, SLC6A4, TP53, and TPH1. However, some of these have later been questioned. Microdeletions and microduplications have been found to be three times more common in individuals with schizophrenia, compared to controls. Because these deletions and duplications are in genes that are overexpressed in pathways related to brain development, it is possible that the inheritance of multiple rare variants may contribute to the development of schizophrenia. Several genetic disorders feature schizophrenia as a clinical feature. The 22q11.2 Deletion Syndrome comprises many different syndromes, of which one of the most serious is DiGeorge syndrome. Children born with DiGeorge syndrome typically have heart defects, cleft palate, learning difficulties, and immune deficiency. Schizophrenia is a late manifestation, affecting around 30% of individuals. Microdeletions and duplications in chromosome 1, 2, 3, 7, 15 and 16 have also been associated with schizophrenia. In 2014, a genome-wide association study looked at the genomes of over 35,000 patients and 110,00 controls. The study identified 108 SNPs that were associated with schizophrenia, 83 of which had not been previously reported. As expected, many of these loci occurred in genes that are expressed in the brain. For example, the SNPs included a gene that encodes the dopamine D2 receptor, DRD2 (the target of antipsychotic drugs), and many genes involved in glutamine neurotransmitter pathways and synaptic plasticity (e.g., GRM3, GRIN2A, SRR, GRIA1). More surprisingly, however, associations were also enriched among genes expressed in tissues with important immune functions. In 2016, a study based on nearly 65,000 people investigated the association between schizophrenia and variation in the Major Histocompatibility Complex (MHC) locus—a region on chromosome 6 that is important for immune function. The study focused on the C4 gene (complement component 4) that exists as two distinct genes: C4A and C4B, which encode particularly structurally diverse alleles. The study found that the alleles which promoted greater expression of C4A in the brain were associated with a greater risk of schizophrenia. By using mice models, the study showed that C4 is involved in the elimination of synapses during brain maturation. In humans, “synaptic pruning” is most active during late adolescence, which coincides with the typical onset of symptoms of schizophrenia. It is therefore possible that the inheritance of specific C4A alleles could lead to “run away” synaptic pruning, increasing the risk of schizophrenia. Further research may even determine C4 as a potential therapeutic target. [from Medical Genetics Summaries]

Mild spondyloepiphyseal dysplasia due to COL2A1 mutation with early-onset osteoarthritis is a type 2 collagen-related bone disorder characterized by precocious, generalized osteoarthritis (with onset as early as childhood) and mild, dysplastic spinal changes (flattening of vertebrae, irregular endplates and wedge-shaped deformities) resulting in a mildly short trunk. [from ORDO]

Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will. [from HPO]

Autosomal recessive form of disease. [from MONDO]

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures (resulting from radiologically demonstrable polycystic osseous lesions), frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. The clinical course of PLOSL can be divided into four stages: 1. The latent stage is characterized by normal early development. 2. The osseous stage (3rd decade of life) is characterized by pain and tenderness, mostly in ankles and feet, usually following strain or injury. Fractures are typically diagnosed several years later, most commonly in the bones of the extremities. 3. In the early neurologic stage (4th decade of life), a change of personality begins to develop insidiously. Affected individuals show a frontal lobe syndrome (loss of judgment, euphoria, loss of social inhibitions, disturbance of concentration, and lack of insight, libido, and motor persistence) leading to serious social problems. 4. The late neurologic stage is characterized by progressive dementia and loss of mobility. Death usually occurs before age 50 years. [from GeneReviews]

A term referring to disorders characterized by abnormalities in the development of bones and cartilage. [from NCI]

An inflammation of brain parenchyma due to infection with a virus. Viral encephalitis can occur as a rare complication of common infections (eg, herpes virus infections) or can occur as a characteristic presentation of rare viruses (eg, rabies virus infection). Encephalitis may be the only neurologic manifestation of infection, or may occur in association with meningitis, myelitis, radiculitis, or neuritis. Viral encephalitis is associated with neurological dysfunction. [from HPO]

A highly contagious viral infection caused by the measles virus. Symptoms appear 8-12 days after exposure and include a rash, cough, fever and muscle pains that can last 4-7 days. Measles vaccines are available to provide prophylaxis, usually combined with mumps and rubella vaccines (MMR). [from NCI]

An inflammatory process affecting the brain parenchyma. Causes include viral infections and less frequently bacterial infections, toxins, and immune-mediated processes. [from NCI]

Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by persistent central nervous system infection with the measles virus (summary by Torisu et al., 2004). [from OMIM]

An inherited metabolic disorder caused by an enzyme deficiency, resulting in an inability to oxidize fatty acids for energy production. [from NCI]

Infections with viruses of the genus morbillivirus, family paramyxoviridae. Infections mainly cause acute disease in their hosts, although in some cases infection is persistent and leads to degenerative conditions. [from MONDO]

Infections with viruses of the order mononegavirales. The concept includes filoviridae infections; paramyxoviridae infections; and rhabdoviridae infections. [from MONDO]

Any disorder of development of the bone. [from NCI]

Viral infections of the brain, spinal cord, meninges, or perimeningeal spaces. [from MeSH]

A disorder of the brain caused by an infectious agent that presents with fever, headache, and an altered level of consciousness. There may also be focal or multifocal neurologic deficits, and focal or generalized seizure activity. [from HPO]