- Stage 5 chronic kidney disease (HP:0003774): 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. Evidence: PCS. Frequency: 5/9. (PMID:28165343)
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: PCS. (PMID:28165343)
- Strabismus (HP:0000486): A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error. Evidence: IEA. (OMIM:617575)
- Nephrotic syndrome (HP:0000100): 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. Evidence: IEA. (OMIM:617575)
- Seizure (HP:0001250): 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. Evidence: IEA. (OMIM:617575)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: PCS. Frequency: 2/8. (PMID:28165343)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 6/8. (PMID:28165343)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: IEA. (OMIM:617575)
- Hypoalbuminemia (HP:0003073): The concentration of albumin in the blood circulation is below the lower limit of normal. Evidence: IEA. (OMIM:617575)
- Podocyte foot process effacement (HP:0031266): An anomaly of podocyte morphology characterized by the loss of the interdigitating foot process pattern (generally called foot process effacement; FPE). The term FPE designates the loss of the usual interdigitating pattern of foot processes of neighboring podocytes, leading to relatively broad expanses of podocyte processes covering the glomerular basement membrane (GBM). It is widely viewed as a pathological derangement that is associated with leakage of macromolecules such as albumin through the glomerular filtration barrier. Evidence: PCS. (PMID:28165343)
- Steroid-resistant nephrotic syndrome (HP:0012588): A form of nephrotic syndrome that does not respond to treatment with steroid medication, defined as persistent proteinuria despite 60mg/m2 or 2mg/kg for 8 weeks, after insuring no infection or non-adherence to medication. Evidence: PCS. Frequency: 5/8. (PMID:28165343)
- Mesangial hypercellularity (HP:0012574): Increased numbers of mesangial cells per glomerulus, defined as more than 3 nuclei fully surrounded by matrix in one or more mesangial areas, not including perihilar region, on a standard 3-micron-thick tissue section, best evaluated on periodic acid-Schiff (PAS) stain. Evidence: PCS. Frequency: 2/4. (PMID:28165343)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. Frequency: 1/8. (PMID:28165343)
- Hypoglycemia (HP:0001943): A decreased concentration of glucose in the blood. Evidence: IEA. (OMIM:617575)
- Decreased total lymphocyte count (HP:0001888): A reduced number of lymphocytes in the blood. Evidence: PCS. Frequency: 2/8. (PMID:28165343)
- Hyperpigmentation of the skin (HP:0000953): A darkening of the skin related to an increase in melanin production and deposition. Evidence: PCS. Frequency: 8/8. (PMID:28165343)
- Diffuse mesangial sclerosis (HP:0001967): Thickening and scarring (sclerosis) of the mesangium (a structure in the glomerulus). The sclerosis affects a large portion of the mesangium across multiple glomeruli. Histologic features include an increase in the mesangial matrix, thickened glomerular basement membrane, tubular casts, and interstitial inflammation. Diffuse mesangial sclerosis presents with nephrotic syndrome at birth or within the first year of life. Glomeruli are small and condensed in appearance, with early lesions showing increased loose mesangial collagen that progress to sclerosis with dense collagen without hypercellularity. Podocytes do not show hyperplasia but may be immature and cobblestone-like. Electron microscopy shows extensive foot process effacement without deposits, but increased collagen within mesangial areas. Evidence: IEA. (OMIM:617575)
- Hypogonadism (HP:0000135): A decreased functionality of the gonad. Evidence: IEA. (OMIM:617575)
- Mental deterioration (HP:0001268): Loss of previously present mental abilities, generally in adults. Evidence: IEA. (OMIM:617575)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: IEA. (OMIM:617575)
- Micropenis (HP:0000054): Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm. Evidence: IEA. (OMIM:617575)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 1/8. (PMID:28165343)
- Hypertriglyceridemia (HP:0002155): An abnormal increase in the level of triglycerides in the blood. Evidence: IEA. (OMIM:617575)
- Developmental regression (HP:0002376): Loss of developmental skills, as manifested by loss of developmental milestones. Evidence: PCS. Frequency: 1/8. (PMID:28165343)
- Focal segmental glomerulosclerosis (HP:0000097): Segmental accumulation of scar tissue in individual (but not all) glomeruli. Evidence: PCS. Frequency: 2/4. (PMID:28165343)
- Global developmental delay (HP:0001263): 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. Evidence: PCS. Frequency: 3/8. (PMID:28165343)
- Proteinuria (HP:0000093): Increased levels of protein in the urine. Evidence: PCS. (PMID:28165343)
- Ichthyosis (HP:0008064): An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization. Evidence: PCS. Frequency: 4/5. (PMID:28165343)
- Edema (HP:0000969): An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body. Evidence: IEA. (OMIM:617575)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: PCS. Frequency: 2/8. (PMID:28165343)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: IEA. (OMIM:617575)
- Peripheral neuropathy (HP:0009830): Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course. Evidence: IEA. (OMIM:617575)
- Autosomal recessive inheritance (HP:0000007): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:28165343)
- Hypothyroidism (HP:0000821): Deficiency of thyroid hormone. Evidence: PCS. Frequency: 4/4. (PMID:28165343)
- Adrenal insufficiency (HP:0000846): Insufficient production of steroid hormones (primarily cortisol) by the adrenal glands. Evidence: PCS. (PMID:28165343)
- Cryptorchidism (HP:0000028): Testis in inguinal canal. That is, absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the scrotum. Evidence: PCS. (PMID:28165343)
These phenotypes are associated with the disease nephrotic syndrome 14 (OMIM:617575).