MedGen

Oculomotor-abducens synkinesis (OCABSN) is an autosomal recessive disorder characterized by a specific anomaly of extraocular muscle movements involving the oculomotor nerve (cranial nerve III) and the abducens nerve (cranial nerve VI). The superior branch of CN3 innervates the levator palpebrae superioris muscle, which raises the eyelid, and CN6 innervates the lateral rectus muscle, which controls lateral eye movement. Affected individuals show ptosis as well as elevation of the eyelid on ipsilateral abduction. The features indicate abnormal innervation of these muscles and suggest synkinesis of the oculomotor and abducens nerves. The disorder can be classified as a congenital cranial dysinnervation disorder (CCDD), and also shows features of congenital fibrosis of the extraocular muscles (CFEOM; see 135700) (summary by Khan et al., 2004 and Whitman et al., 2019). See also oculomotor-levator synkinesis (OCLEVS; 151610), a similar disorder. [from OMIM]

WHIM syndrome-2 (WHIMS2) is an autosomal recessive immunologic disorder characterized by chronic neutropenia and myelokathexis, which is impaired neutrophil mobilization from the bone marrow. Affected individuals have recurrent infections, usually bacterial (summary by Auer et al., 2014). In a review of WHIMS, Heusinkveld et al. (2019) noted that there is significant phenotypic variation among patients, such that some individuals may have an 'incomplete' form of the disorder in which 1 or more of the classic tetrad features are not present. In general, the WHIMS phenotype comprises a spectrum of manifestations with variable expressivity. For a discussion of genetic heterogeneity of WHIMS, see 193670. [from OMIM]

WHIM syndrome-1 (WHIMS1) is an autosomal dominant immunologic disorder characterized by neutropenia, hypogammaglobulinemia, and warts due to human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis. The susceptibility to HPV is disproportionate compared with other immunodeficiency conditions (summary by Hernandez et al., 2003). Heusinkveld et al. (2019) provided a detailed review of the clinical features, proposed pathogenesis, and possible therapeutic treatments of WHIM syndrome. There is significant phenotypic variation among patients, such that some individuals may have an 'incomplete' form of the disorder in which one or more of the classic tetrad features are not present. In general, the WHIMS phenotype comprises a spectrum of manifestations with variable expressivity. The pathogenesis of WHIMS1 is postulated to result from impaired CXCL12 (600835)-induced internalization of CXCR4, resulting in prolonged receptor presence at the cell surface that likely contributes to amplification of signaling with a gain-of-function effect. Genetic Heterogeneity of WHIM Syndrome See also WHIMS2 (619407), caused by mutation in the CXCR2 gene (146928) on chromosome 2q35. [from OMIM]

Polycystic lung disease (PCLUD) is an autosomal recessive disorder characterized by childhood-onset exertional dyspnea and cough due to progressive airflow obstruction in the lungs. Pulmonary imaging shows diffuse lung disease with pleural and subpleural cysts and peripheral consolidations, and lung biopsy shows bronchiolitis and lymphocytosis of the terminal bronchioles, often with features of pulmonary alveolar proteinosis (PAP). Most affected individuals have recurrent respiratory infections; some have an adverse response to BCG vaccination. Additional features may include digital clubbing, allergies, and atopic dermatitis (et al., 2024). [from OMIM]

Age-related macular degeneration is an eye disease that is a leading cause of vision loss in older people in developed countries. Subtle abnormalities indicating changes in vision may occur in a person's forties or fifties. Distorted vision and vision loss usually become noticeable in a person's sixties or seventies and tend to worsen over time.

Age-related macular degeneration mainly affects central vision, which is needed for detailed tasks such as reading, driving, and recognizing faces. The vision loss in this condition results from a gradual deterioration of light-sensing cells in the tissue at the back of the eye that detects light and color (the retina). Specifically, age-related macular degeneration affects a small area near the center of the retina, called the macula, which is responsible for central vision. Side (peripheral) vision and night vision are generally not affected, but slow adjustment of vision to darkness (dark adaptation) and reduced dim light (scotopic) vision often occur in the early stages of the disease.

Researchers have described two major types of age-related macular degeneration, known as the dry form and the wet form. The dry form is much more common, accounting for 85 to 90 percent of all cases of age-related macular degeneration. It is characterized by a buildup of yellowish deposits called drusen beneath the retina and vision loss that worsens slowly over time. The most advanced stage of dry age-related macular degeneration is known as geographic atrophy, in which areas of the macula waste away (atrophy), resulting in severe vision loss. Dry age-related macular degeneration typically affects vision in both eyes, although vision loss often occurs in one eye before the other.

In 10 to 15 percent of affected individuals, the dry form progresses to the wet form of age-related macular degeneration. The wet form is characterized by the growth of abnormal, fragile blood vessels underneath the macula. These vessels leak blood and fluid, which damages the macula and makes central vision appear blurry and distorted. The wet form of age-related macular degeneration is associated with severe vision loss that can worsen rapidly. [from MedlinePlus Genetics]

Maraviroc is a chemokine receptor antagonist that is used in combination with other antiretroviral agents to treat human immunodeficiency virus type 1 (HIV-1) infection. Maraviroc exerts its therapeutic activity by blocking entry of the HIV-1 virus into immune cells—specifically the CD4-expressing T-helper cells, which play a major role in protecting the body from infection—precursor cells, and dendritic cells. HIV-1 infection is classified in two major forms according to the co-receptor it employs to gain entry in to the cell, namely the chemokine receptor 5 (CCR5) or the CXC chemokine receptor 4 (CXCR4). These co-receptors are expressed on different types of cells, and HIV tropism refers to the types of cells and tissues in which the virus infects and replicates. A tropism assay is conducted to determine which co-receptor the HIV-1 virus uses, i.e., whether the virus is CCR5-tropic, CXCR4-tropic, dual tropic (i.e., HIV-1 virus that is able to use both receptors), or mixed tropic (i.e., a mixture of HIV-1 viruses, some of which use CCR5 and others that use CXCR4). Maraviroc is only indicated for treatment of adults with CCR5 tropic HIV-1 and is not recommended when the CXCR4-tropic virus has been detected. The FDA-approved drug label for maraviroc states that “prior to initiation of maraviroc, test all patients for CCR5 tropism using a highly sensitive tropism assay”. [from Medical Genetics Summaries]

Uncontrolled type 1 diabetes can lead to a life-threatening complication called diabetic ketoacidosis. Without insulin, cells cannot take in glucose. A lack of glucose in cells prompts the liver to try to compensate by releasing more glucose into the blood, and blood glucose can become extremely high. The cells, unable to use the glucose in the blood for energy, respond by using fats instead. Breaking down fats to obtain energy produces waste products called ketones, which can build up to toxic levels in people with type 1 diabetes, resulting in diabetic ketoacidosis. Affected individuals may begin breathing rapidly; develop a fruity odor in the breath; and experience nausea, vomiting, facial flushing, stomach pain, and dryness of the mouth (xerostomia). In severe cases, diabetic ketoacidosis can lead to coma and death.

Over many years, the chronic high blood glucose associated with diabetes may cause damage to blood vessels and nerves, leading to complications affecting many organs and tissues. The retina, which is the light-sensitive tissue at the back of the eye, can be damaged (diabetic retinopathy), leading to vision loss and eventual blindness. Kidney damage (diabetic nephropathy) may also occur and can lead to kidney failure and end-stage renal disease (ESRD). Pain, tingling, and loss of normal sensation (diabetic neuropathy) often occur, especially in the feet. Impaired circulation and absence of the normal sensations that prompt reaction to injury can result in permanent damage to the feet; in severe cases, the damage can lead to amputation. People with type 1 diabetes are also at increased risk of heart attacks, strokes, and problems with urinary and sexual function.

Type 1 diabetes can occur at any age, from early childhood to late adulthood. The first signs and symptoms of the disorder are caused by high blood glucose and may include frequent urination (polyuria), excessive thirst (polydipsia), fatigue, blurred vision, tingling or loss of feeling in the hands and feet, and weight loss. These symptoms may recur during the course of the disorder if blood glucose is not well controlled by insulin replacement therapy. Improper control can also cause blood glucose levels to become too low (hypoglycemia). This may occur when the body's needs change, such as during exercise or if eating is delayed. Hypoglycemia can cause headache, dizziness, hunger, shaking, sweating, weakness, and agitation.

Type 1 diabetes is a disorder characterized by abnormally high levels of blood glucose, also called blood sugar. In this form of diabetes, specialized cells in the pancreas called beta cells stop producing insulin. Insulin controls how much glucose (a type of sugar) is passed from the blood into cells for conversion to energy. Lack of insulin results in the inability to use glucose for energy or to control the amount of glucose in the blood. [from MedlinePlus Genetics]

Any coronary artery disease in which the cause of the disease is a mutation in the CX3CR1 gene. [from MONDO]

WNV is an enveloped, neurotropic, single-stranded sense RNA flavivirus that is naturally maintained in a zoonotic cycle between avian hosts and mosquito vectors. The virus was first isolated from a Ugandan woman in 1937 and subsequently emerged in Europe and, in 1999, in New York, with eventual spread throughout North America. WNV causes a spectrum of disease ranging from acute fever to lethal encephalitis. Susceptibility to WNV is increased in the elderly and in immunocompromised individuals (summary by Diamond and Klein (2006) and Glass et al. (2005)). [from OMIM]

The pathogenesis of HIV infection and the progression from infection to AIDS vary significantly between exposed individuals. Infection occurs after the virus, which has macrophage (M)- and T lymphocyte (T)-tropic strains and more than 12 subtypes, survives an array of nonspecific, nongenetic environmental and host factors. [from OMIM]

HCV, which is principally transmitted by blood, infects about 3% of the world's population. HCV infection causes acute hepatitis, which is self-resolving in 20 to 50% of cases but does not confer permanent immunity. In 50 to 80% of cases, HCV infection becomes chronic and results in chronic hepatitis, cirrhosis, and hepatocellular carcinoma. As a result, HCV infection is a leading killer worldwide and the most common cause of liver failure in the U.S. HCV is opportunistic in individuals infected with human immunodeficiency virus (HIV; see 609423), approximately 25% of whom are coinfected with HCV. HCV infection is also associated with cryoglobulinemia (see 123550), a B-lymphocyte proliferative disorder (Pawlotsky, 2004; Chisari (2005); Pileri et al., 1998). [from OMIM]