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.

Diffuse sclerosis of the mesangium, as manifestated by diffuse mesangial matrix expansion.

A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.

The nephrotic syndrome is characterized clinically by proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Kidney biopsies show nonspecific histologic changes such as minimal change, focal segmental glomerulosclerosis (FSGS), and diffuse mesangial proliferation. Approximately 20% of affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure (summary by Fuchshuber et al., 1996). Nephrotic syndrome type 1 (NPHS1) is characterized by prenatal onset of massive proteinuria followed by severe steroid-resistant nephrotic syndrome apparent at birth with rapid progression to end-stage renal failure (Kestila et al., 1998). Because of confusion in the literature regarding use of the terms 'nephrotic syndrome' and 'focal segmental glomerulosclerosis' (see NOMENCLATURE section), these disorders in OMIM are classified as NPHS or FSGS according to how they were first designated in the literature. Genetic Heterogeneity of Nephrotic Syndrome and Focal Segmental Glomerulosclerosis Nephrotic syndrome and FSGS are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also NPHS2 (600995), caused by mutation in the podocin gene (604766); NPHS3 (610725), caused by mutation in the PLCE1 gene (608414); NPHS4 (256370), caused by mutation in the WT1 gene (607102); NPHS5 (614199), caused by mutation in the LAMB2 gene (150325); NPHS6 (614196), caused by mutation in the PTPRO gene (600579); NPHS7 (615008), caused by mutation in the DGKE gene (601440); NPHS8 (615244), caused by mutation in the ARHGDIA gene (601925); NPHS9 (615573), caused by mutation in the COQ8B gene (615567); NPHS10 (615861), caused by mutation in the EMP2 gene (602334); NPHS11 (616730), caused by mutation in the NUP107 gene (607617); NPHS12 (616892), caused by mutation in the NUP93 gene (614351); NPHS13 (616893), caused by mutation in the NUP205 gene (614352); NPHS14 (617575), caused by mutation in the SGPL1 gene (603729); NPHS15 (617609), caused by mutation in the MAGI2 gene (606382); NPHS16 (617783), caused by mutation in the KANK2 gene (614610), NPHS17 (618176), caused by mutation in the NUP85 gene (170285); NPHS18 (618177), caused by mutation in the NUP133 gene (607613); NPHS19 (618178), caused by mutation in the NUP160 gene (607614); NPHS20 (301028), caused by mutation in the TBC1D8B gene (301027); NPHS21 (618594) caused by mutation in the AVIL gene (613397); NPHS22 (619155), caused by mutation in the NOS1AP gene (605551); NPHS23 (619201), caused by mutation in the KIRREL1 gene (607428); NPHS24 (619263), caused by mutation in the DAAM2 gene (606627); and NPHS26 (620049), caused by mutation in the LAMA5 gene (601033). The symbol NPHS25 has been used as an alternative designation for NPHS21. See also FSGS1 (603278), caused by mutation in the ACTN4 gene (604638); FSGS2 (603965), caused by mutation in the TRPC6 gene (603652); FSGS3 (607832), associated with variation in the CD2AP gene (604241); FSGS4 (612551), mapped to chromosome 22q12; FSGS5 (613237), caused by mutation in the INF2 gene (610982); FSGS6 (614131), caused by mutation in the MYO1E gene (601479); FSGS7 (616002), caused by mutation in the PAX2 gene (167409); FSGS8 (616032), caused by mutation in the ANLN gene (616027); and FSGS9 (616220), caused by mutation in the CRB2 gene (609720).

The gradual reduction in girth of the finger from proximal to distal.

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).

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).

A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.

Polymicrogyria is a congenital malformation of the cerebral cortex characterized by abnormal cortical layering (lamination) and an excessive number of small gyri (folds).

Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.

A degree of language development that is significantly below the norm for a child of a specified age.

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.

Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

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.

Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.

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

Forward protrusion of the glabella.

A hyperpigmented circumscribed area of change in normal skin color without elevation or depression of any size.

Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.