Segmental accumulation of scar tissue in individual (but not all) glomeruli.

Nephrotic syndrome is a collection of findings resulting from glomerular dysfunction with an increase in glomerular capillary wall permeability associated with pronounced proteinuria. Nephrotic syndrome refers to the constellation of clinical findings that result from severe renal loss of protein, with Proteinuria and hypoalbuminemia, edema, and hyperlipidemia.

Increased levels of protein in the urine.

An abnormal increase in the size of the kidney.

The presence of renal tubules with thick redundant basement membranes, or a reduction of greater than 50% in tubular diameter compared to surrounding non-atrophic tubules.

Broadening of the soft tissues (non-edematous swelling of soft tissues) of the digital tips in all dimensions associated with an increased longitudinal and lateral curvature of the nails.

A smaller than normal acetabulum that has insufficient femoral head coverage leading to abnormal hip joint contact pressures, instability and pain.

Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.

In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.

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.

Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.

Abnormally increased size of the liver.

A form of hepatic steatosis characterized by the presence of large, lipid-laden vesicles in the affected hepatocytes.

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

Incapability to ambulate.

Reduction of neurologic reflexes such as the knee-jerk reaction.

A type of Developmental delay characterized by a delay in acquiring motor skills.

Complete lack of development of speech and language abilities.

Delayed myelination in the central nervous system.

Partial or complete wasting (loss) of brain tissue that was once present.

A reduction in erythrocytes volume or hemoglobin concentration.

A reduction in the number of circulating thrombocytes.

A reduced number of hematopoietic cells present in the bone marrow relative to marrow fat.

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap. Affected individuals are best described as having either a phenotype consistent with either severe (Hurler syndrome) or attenuated MPS I, a distinction that influences therapeutic options. Severe MPS I. Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal, as is progressive arthropathy involving most joints. By age three years, linear growth decreases. Intellectual disability is progressive and profound but may not be readily apparent in the first year of life. Progressive cardiorespiratory involvement, hearing loss, and corneal clouding are common. Without treatment, death (typically from cardiorespiratory failure) usually occurs within the first ten years of life. Attenuated MPS I. Clinical onset is usually between ages three and ten years. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decade, to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities and psychiatric manifestations can be present later in life. Hearing loss, cardiac valvular disease, respiratory involvement, and corneal clouding are common.

A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.

The presence of calcium deposition within the cerebrum.

A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.

Abnormal widening of the metaphyseal regions of long bones.

A deformity of the sella turcica whereby the sella extends further anterior than normal such that the anterior clinoid process appears to overhang it, giving the appearance of the letter J on imaging of the skull.

Widening of the ilium ala, that is of the wing of the ilium, combined with external rotation, leading to a flared appearance of the iliac wing.

A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.

Head circumference below 2 standard deviations below the mean for age and gender.

Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.

An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.

An increased susceptibility to bronchopulmonary infections as manifested by a history of recurrent bronchopulmonary infections.

An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.

An abnormal decreased number of leukocytes in the blood.

The presence of inflammation affecting the kidney.

Systemic inflammatory response to infection.

Abnormal increased size of the spleen.

An abnormally low number of neutrophils in the peripheral blood.

An abnormally increased level of immunoglobulin M in blood.

Reduction in the concentration of albumin in the blood.

Increased length and width of the tongue.

Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.

Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.

Diminished length of the neck.

Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).

Increased width of the skin of vermilion border region of upper lip.

Forward prominence of the entire forehead, due to protrusion of the frontal bone.

Distance between the hairline (trichion) and the glabella (the most prominent point on the frontal bone above the root of the nose), in the midline, more than two SD below the mean. Alternatively, an apparently decreased distance between the hairline and the glabella.

Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.

Increased breadth of the nasal bridge (and with it, the nasal root).

Hair on the neck extends more inferiorly than usual.

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

Laminar thickening of skin.

Hair shafts are rough in texture.

Meeting of the medial eyebrows in the midline.

Mid upper eyelash length >10 mm or increased length of the eyelashes (subjective).

Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.