MedGen

A reduction of bone mineral density, that is, of the amount of matter per cubic centimeter of bones. [from HPO]

A rare stiff person syndrome spectrum disorder characterized by limb and truncal rigidity, stimulus-sensitive spasms, myoclonus, hyperekplexia, autonomic disturbance, and brainstem involvement or other neurological defects. The condition is progressive and potentially life-threatening, especially due to respiratory failure. It may be associated with the presence of glycine receptor or glutamic acid decarboxylase antibodies, as well as thymomas or lymphomas. [from ORDO]

A slower than normal heart rate (in adults, slower than 60 beats per minute). [from HPO]

Uveal melanoma is a highly malignant tumor that arises from the choroid or the ciliary body of the eye. It is the most common primary ocular malignancy in adults, although it has a low incidence (6 cases per 1,000,000 per year). A tendency for hematogenic spread to the liver accounts for up to 50% of patient deaths (summary by Lopez et al., 2007). [from OMIM]

Familial paroxysmal nonkinesigenic dyskinesia (PNKD) is characterized by unilateral or bilateral involuntary movements. Attacks are typically precipitated by coffee, tea, or alcohol; they can also be triggered by excitement, stress, or fatigue, or can be spontaneous. Attacks involve dystonic posturing with choreic and ballistic movements, may be accompanied by a preceding aura, occur while the individual is awake, and are not associated with seizures. Attacks last minutes to hours and rarely occur more than once per day. Attack frequency, duration, severity, and combinations of symptoms vary within and among families. Age of onset is typically in childhood or early teens but can be as late as age 50 years. [from GeneReviews]

Cataract is an opacification of the lens or lens capsule in the eye and is the most common cause of childhood blindness in the world, with an incidence of 1 to 3 per 10,000 live births. If untreated in infancy or childhood, it frequently causes visual impairment and can result in irreversible amblyopia. Nuclear cataract refers to opacification within the embryonal and/or fetal nuclei of the lens (summary by Berry et al., 2013). [from OMIM]

Aplastic anemia is a serious disorder of the bone marrow that affects between 2 and 5 persons per million per year. About 75% of these cases are classified as idiopathic (Young, 2000). In about 15% of cases a drug or infection can be identified that precipitates the aplasia, although why only some individuals are susceptible is unclear. In about 5 to 10% of patients, the aplastic anemia is constitutional--i.e., is familial or presents with one or more associated somatic abnormalities (summary by Vulliamy et al., 2002). [from OMIM]

An atrial arrhythmia characterized by disorganized atrial activity without discrete P waves on the surface EKG, but instead by an undulating baseline or more sharply circumscribed atrial deflections of varying amplitude an frequency ranging from 350 to 600 per minute. [from HPO]

Waldenstrom macroglobulinemia (WM) is a malignant B-cell neoplasm characterized by lymphoplasmacytic infiltration of the bone marrow and hypersecretion of monoclonal immunoglobulin M (IgM) protein (review by Vijay and Gertz, 2007). The importance of genetic factors is suggested by the observation of familial clustering of WM (McMaster, 2003). Whereas WM is rare, an asymptomatic elevation of monoclonal IgM protein, termed 'IgM monoclonal gammopathy of undetermined significance' (IgM MGUS) is more common. Patients with IgM MGUS can progress to develop WM, at the rate of 1.5% to 2% per year (Kyle et al., 2003). Genetic Heterogeneity of Waldenstrom Macroglobulinemia A locus for susceptibility to Waldenstrom macroglobulinemia (WM2; 610430) has been mapped to chromosome 4q. [from OMIM]

Increased density of hairs, i.e., and elevated number of hairs per unit area. [from HPO]

Pulmonary venoocclusive disease primarily affects the postcapillary venous pulmonary vessels and may involve significant pulmonary capillary dilation and/or proliferation. PVOD is an uncommon cause of pulmonary artery hypertension (PPH; see 178600), a severe condition characterized by elevated pulmonary artery pressure leading to right heart failure and death. PVOD accounts for 5 to 10% of 'idiopathic' PPH and has an estimated incidence of 0.1 to 0.2 cases per million. The pathologic hallmark of PVOD is the extensive and diffuse occlusion of pulmonary veins by fibrous tissue, with intimal thickening present in venules and small veins in lobular septa and, rarely, larger veins. Definitive diagnosis of PVOD requires histologic analysis of a lung sample, although surgical lung biopsy is often too invasive for these frail patients. Patients with PVOD respond poorly to available therapy, therefore it is crucial to distinguish PVOD from other forms of PPH. Radiologic characteristics suggestive of PVOD on high-resolution CT of the chest include nodular ground-glass opacities, septal lines, and lymph node enlargement. In addition, because PVOD mainly affects postcapillary vasculature, it causes chronic elevation of pulmonary capillary pressure and thus promotes occult alveolar hemorrhage, which may be a characteristic feature of PVOD (summary by Montani et al., 2008). Genetic Heterogeneity of Pulmonary Venoocclusive Disease See also PVOD2 (234810), caused by mutation in the EIF2AK4 gene (609280) on chromosome 15q15. [from OMIM]

Capillary hemangiomas are benign, highly proliferative lesions involving aberrant localized growth of capillary endothelium. They are the most common tumor of infancy, occurring in up to 10% of all births (Mulliken and Young, 1988). Hemangiomas tend to appear shortly after birth and show rapid neonatal growth for up to 12 months characterized by endothelial hypercellularity and increased numbers of mast cells. This phase is followed by slow involution at a rate of about 10% per year and replacement by fibrofatty stroma. Hemangiomas are classified as distinct from vascular malformations (see, e.g., CMC1, 163000; 108010; and CCM, 116860), in that the latter are present from birth, tend to grow with the individual, do not regress, and show normal rates of endothelial cell turnover (Spring and Bentz, 2005; Legiehn and Heran, 2006). Legiehn and Heran (2006) noted that the term 'hemangioma' in adults is considered inaccurate and should be discarded. Most hemangiomas occur sporadically, but some families with autosomal dominant inheritance have been reported (Walter et al., 1999). [from OMIM]

A well differentiated, low grade neuroendocrine neoplasm (carcinoid tumor) that arises from the small or large intestine. The mitotic count is less than 2 per 10 HPF and/or the Ki67 index is equal to or less than 2 percent. [from NCI]

A reduction in the count of nephrons per kidney. [from HPO]

Number of leukocytes per volume of blood beyond normal limits. [from HPO]

A severe form of age-related epileptic encephalopathies characterized by the onset of tonic spasms within the first 3 months of life that can be generalized or lateralized, independent of the sleep cycle, and that can occur hundreds of times per day, leading to psychomotor impairment and death. [from ORDO]

Decreased number of hairs per unit area of skin of the scalp. [from HPO]

Brivaracetam (brand name Briviact) is an antiseizure drug used in the treatment of partial-onset (focal) epilepsy in adults. It is thought to act by binding to a synaptic vesicle glycoprotein, SV2A, and reducing the release of neurotransmitters. Brivaracetam is primarily metabolized by hydrolysis, via amidase enzymes, to an inactive metabolite. To a lesser extent, it is also metabolized by a minor metabolic pathway via CYP2C19-dependent hydroxylation. Individuals who have no CYP2C19 enzyme activity, "CYP2C19 poor metabolizers", will have a greater exposure to standard doses of brivaracetam. Because they are less able to metabolize the drug to its inactive form for excretion, they may have an increased risk of adverse effects. The most common adverse effects of brivaracetam therapy include sedation, fatigue, dizziness, and nausea. The recommended starting dosage for brivaracetam monotherapy or adjunctive therapy is 50 mg twice daily (100 mg per day). Based on how the individual responds, the dose of brivaracetam may be decreased to 25 mg twice daily (50 mg per day) or increased up to 100 mg twice daily (200 mg per day). The FDA-approved drug label for brivaracetam states that patients who are CYPC19 poor metabolizers, or are taking medicines that inhibit CYP2C19, may require a dose reduction. Approximately 2% of Caucasians, 4% of African Americans, and 14% of Chinese are CYP2C19 poor metabolizers. [from Medical Genetics Summaries]

Arteriovenous malformations of the brain are tortuous, morphologically abnormal vascular channels between arteries and veins that lack an intervening capillary network, allowing high-pressure arterial blood from feeding arteries to shunt directly into the venous outflow system. These vascular malformations occur in approximately 15 per 100,000 persons and are a leading cause of hemorrhagic stroke in young adults and children (summary by Nikolaev et al., 2018). [from OMIM]