Pain in muscle.

The occurrence of an unusually high amount of muscle pain following exercise.

Increased concentration of albumin in the urine.

Amenorrhea due to loss of ovarian function before the age of 40. Primary ovarian insuficiency (POI) is a state of female hypergonadotropic hypogonadism. It can manifest as primary amenorrhea with onset before menarche or secondary amenorrhea.

Polycystic ovary syndrome is a condition that affects women in their child-bearing years and alters the levels of multiple hormones, resulting in problems affecting many body systems.\n\nMost women with polycystic ovary syndrome produce excess male sex hormones (androgens), a condition called hyperandrogenism. Having too much of these hormones typically leads to excessive body hair growth (hirsutism), acne, and male pattern baldness.\n\nHyperandrogenism and abnormal levels of other sex hormones prevent normal release of egg cells from the ovaries (ovulation) and regular menstrual periods, leading to difficulty conceiving a child (subfertility) or a complete inability to conceive (infertility). For those who achieve pregnancy, there is an increased risk of complications and pregnancy loss. Due to irregular and infrequent menstruation and hormone abnormalities, affected women have an increased risk of cancer of the uterine lining (endometrial cancer).\n\nIn polycystic ovary syndrome, one or both ovaries can contain multiple small, immature ovarian follicles that can appear as cysts on medical imaging. Normally, ovarian follicles contain egg cells, which are released during ovulation. In polycystic ovary syndrome, abnormal hormone levels prevent follicles from growing and maturing to release egg cells. Instead, these immature follicles accumulate in the ovaries. Affected women can have 12 or more of these follicles. The number of these follicles usually decreases with age.\n\nAbout half of all women with polycystic ovary syndrome are overweight or have obesity and are at increased risk of a fatty liver. Additionally, many women with polycystic ovary syndrome have elevated levels of insulin, which is a hormone that helps control levels of blood glucose, also called blood sugar. By age 40, about 10 percent of overweight women with polycystic ovary syndrome develop abnormally high blood glucose levels (type 2 diabetes), and up to 35 percent develop prediabetes (higher-than-normal blood glucose levels that do not reach the cutoff for diabetes). Obesity and increased insulin levels (hyperinsulinemia) further increase the production of androgens in polycystic ovary syndrome.\n\nWomen with polycystic ovary syndrome are also at increased risk for developing metabolic syndrome, which is a group of conditions that include high blood pressure (hypertension), increased belly fat, high levels of unhealthy fats and low levels of healthy fats in the blood, and high blood glucose levels. About 20 percent of affected adults experience pauses in breathing during sleep (sleep apnea). Women with polycystic ovary syndrome are more likely than women in the general popluation to have mood disorders such as depression.

A condition characterized by patchy atheromas or atherosclerotic plaques which develop in the walls of medium-sized and large arteries and can lead to arterial stenosis with reduced or blocked blood flow.

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.

Delayed or lack of conduction of atrial depolarizations through the atrioventricular node to the ventricles.

Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.

The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.

The presence of chronic increased pressure in the systemic arterial system.

Increased time between the start of the Q wave and the end of the T wave as measured by the electrocardiogram (EKG).

A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.

Reduction of the diameter of the coronary arteries as the result of an accumulation of atheromatous plaques within the walls of the coronary arteries before age of 45.

Accumulation of substantial excess body fat.

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

Increased body weight with a body mass index of 25-29.9 kg per square meter.

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Abnormally increased size of the liver.

Steatosis is a term used to denote lipid accumulation within hepatocytes.

Increase in size of a peripheral nerve. This finding can be appreciated by palpation along the axis of the nerve.

Injury to the median nerve caused by its entrapment at the wrist as it traverses through the carpal tunnel. Clinically, constrictive median neuropathy is characterized by pain, paresthesia, and weakness in the median nerve distribution of the hand.

An increased concentration of hemoglobin A1c (HbA1c), which is the product of nonenzymatic attachment of a hexose molecule to the N-terminal amino acid of the hemoglobin molecule. This reaction is dependent on blood glucose concentration, and therefore reflects the mean glucose concentration over the previous 8 to 12 weeks. The HbA1c level provides a better indication of long-term glycemic control than one-time blood or urinary glucose measurements.

Degenerative changes of the fat tissue.

Developmental hypoplasia of the mandible.

A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.

The term dystrophy means abnormal growth. However, muscular dystrophy is used to describe primary myopathies with a genetic basis and a progressive course characterized by progressive skeletal muscle weakness and wasting, defects in muscle proteins, and histological features of muscle fiber degeneration (necrosis) and regeneration. If possible, it is preferred to use other HPO terms to describe the precise phenotypic abnormalities.

Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).

The presence of an abnormal lateral curvature of the spine.

Reduced strength of muscles.

A contracture of the Achilles tendon.

An involuntary and painless delay in the relaxation of skeletal muscle following contraction or electrical stimulation.

Loss (reduction of previously present) of subcutaneous adipose tissue in the region of the trunk.

An abnormal increase in the amount of intramuscular fat tissue.

An abnormal increase in the amount of intraabdominal fat tissue.

Loss (disappearance) of previously present subcutaneous fat tissue in arm or leg.

A reduced amount of fat tissue in the lowest layer of the integument. This feature can be appreciated by a reduced skinfold thickness.

Abnormal increase in muscle size and mass not due to training.

A loss of adipose tissue.

Generalized degenerative changes of the fat tissue.

A acute form of pancreatitis.

The presence of inflammation in the pancreas.

Abnormal increased size of the spleen.

Type 2 diabetes mellitus is distinct from maturity-onset diabetes of the young (see 606391) in that it is polygenic, characterized by gene-gene and gene-environment interactions with onset in adulthood, usually at age 40 to 60 but occasionally in adolescence if a person is obese. The pedigrees are rarely multigenerational. The penetrance is variable, possibly 10 to 40% (Fajans et al., 2001). Persons with type 2 diabetes usually have an obese body habitus and manifestations of the so-called metabolic syndrome (see 605552), which is characterized by diabetes, insulin resistance, hypertension, and hypertriglyceridemia. Genetic Heterogeneity of Susceptibility to Type 2 Diabetes Susceptibility to T2D1 (601283) is conferred by variation in the calpain-10 gene (CAPN10; 605286) on chromosome 2q37. The T2D2 locus (601407) on chromosome 12q was found in a Finnish population. The T2D3 locus (603694) maps to chromosome 20. The T2D4 locus (608036) maps to chromosome 5q34-q35. Susceptibility to T2D5 (616087) is conferred by variation in the TBC1D4 gene (612465) on chromosome 13q22. A mutation has been observed in hepatocyte nuclear factor-4-alpha (HNF4A; 600281.0004) in a French family with NIDDM of late onset. Mutations in the NEUROD1 gene (601724) on chromosome 2q32 were found to cause type 2 diabetes mellitus in 2 families. Mutation in the GLUT2 glucose transporter was associated with NIDDM in 1 patient (138160.0001). Mutation in the MAPK8IP1 gene, which encodes the islet-brain-1 protein, was found in a family with type 2 diabetes in individuals in 4 successive generations (604641.0001). Polymorphism in the KCNJ11 gene (600937.0014) confers susceptibility. In French white families, Vionnet et al. (2000) found evidence for a susceptibility locus for type 2 diabetes on 3q27-qter. They confirmed the diabetes susceptibility locus on 1q21-q24 reported by Elbein et al. (1999) in whites and by Hanson et al. (1998) in Pima Indians. A mutation in the GPD2 gene (138430.0001) on chromosome 2q24.1, encoding mitochondrial glycerophosphate dehydrogenase, was found in a patient with type 2 diabetes mellitus and in his glucose-intolerant half sister. Mutations in the PAX4 gene (167413) have been identified in patients with type 2 diabetes. Triggs-Raine et al. (2002) stated that in the Oji-Cree, a gly319-to-ser change in HNF1-alpha (142410.0008) behaves as a susceptibility allele for type 2 diabetes. Mutation in the HNF1B gene (189907.0007) was found in 2 Japanese patients with typical late-onset type 2 diabetes. Mutations in the IRS1 gene (147545) have been found in patients with type 2 diabetes. A missense mutation in the AKT2 gene (164731.0001) caused autosomal dominant type 2 diabetes in 1 family. A (single-nucleotide polymorphism) SNP in the 3-prime untranslated region of the resistin gene (605565.0001) was associated with susceptibility to diabetes and to insulin resistance-related hypertension in Chinese subjects. Susceptibility to insulin resistance has been associated with polymorphism in the TCF1 (142410.0011), PPP1R3A (600917.0001), PTPN1 (176885.0001), ENPP1 (173335.0006), IRS1 (147545.0002), and EPHX2 (132811.0001) genes. The K121Q polymorphism of ENPP1 (173335.0006) is associated with susceptibility to type 2 diabetes; a haplotype defined by 3 SNPs of this gene, including K121Q, is associated with obesity, glucose intolerance, and type 2 diabetes. A SNP in the promoter region of the hepatic lipase gene (151670.0004) predicts conversion from impaired glucose tolerance to type 2 diabetes. Variants of transcription factor 7-like-2 (TCF7L2; 602228.0001), located on 10q, have also been found to confer risk of type 2 diabetes. A common sequence variant, rs10811661, on chromosome 9p21 near the CDKN2A (600160) and CDKN2B (600431) genes has been associated with risk of type 2 diabetes. Variation in the PPARG gene (601487) has been associated with risk of type 2 diabetes. A promoter polymorphism in the IL6 gene (147620) is associated with susceptibility to NIDDM. Variation in the KCNJ15 gene (602106) has been associated with T2D in lean Asians. Variation in the SLC30A8 gene (611145) has been associated with susceptibility to T2D. Variation in the HMGA1 gene (600701.0001) is associated with an increased risk of type 2 diabetes. Mutation in the MTNR1B gene (600804) is associated with susceptibility to type 2 diabetes. Protection Against Type 2 Diabetes Mellitus Protein-truncating variants in the SLC30A8 (611145) have been associated with a reduced risk for T2D.

An increased concentration of cholesterol in the blood.

An increased concentration of glucose in the blood.

Increased resistance towards insulin, that is, diminished effectiveness of insulin in reducing blood glucose levels.

An decreased concentration of high-density lipoprotein cholesterol in the blood.

The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.

An abnormally high concentration in the circulation of alanine aminotransferase (ALT).

Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).

An elevated concentration of low-density lipoprotein cholesterol in the blood.

An abnormally high level of uric acid in the blood.

An abnormal increase in the level of triglycerides in the blood.

A type of diabetes mellitus related not to lack of insulin but rather to lack of response to insulin on the part of the target tissues of insulin such as muscle, fat, and liver cells. This type of diabetes is typically associated with increases both in blood glucose concentrations as well as in fasting and postprandial serum insulin levels.

An abnormal concentration of creatinine in the blood.

An abnormal elevation of the C-reactive protein level in the blood circulation.

A higher than normal levels of the fatty acids which can occur in plasma as a result of lipolysis in adipose tissue or when plasma triacyglycerols are taken into tissues.

An elevated level of circulating N-terminal part of the prohormone of B-type natriuretic peptide (BNP).

A deviation from the normal concentration of lipoprotein lipase in the blood circulation.

The facial appearance is more circular than usual as viewed from the front.

An increased amount of subcutaneous fat tissue around the neck.

An increased amount of subcutaneous fat tissue in the face.

A dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck.

A noncongenital process of hair loss, which may progress to partial or complete baldness.

A chronic autoimmune phenomenon characterized by fibrosis (or hardening) and vascular alterations of the skin.

Abnormally increased hair growth referring to a male pattern of body hair (androgenic hair).

The presence of multiple xanthomas (xanthomata) in the skin. Xanthomas are yellowish, firm, lipid-laden nodules in the skin.

Patchy and irregular skin pigmentation.

A condition in which superficial veins (i.e., veins just under the skin) are more conspicuous or noticeable than normal.

A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance.

An increased concentration of insulin in the blood.

An eye that is protruding anterior to the plane of the face to a greater extent than is typical.