Spotlight on Hereditary Kidney Disorders

hereditary kidney disorders


Overwhelmingly, most cases of kidney disease are the result of complications of diabetes or high blood pressure. However, roughly 10% of cases are hereditary in nature – a proportion that is significantly higher in children presenting with symptoms of kidney disease.

In fact, there are more than 60 different genetic diseases that can affect kidney function. Many are very rare, but some are relatively common. And all are the focus of specialists practicing in renal genetics clinics. Comprehensive genetic testing can get at the root cause of these hereditary conditions, identifying the likely causal mutation amongst a wide spectrum of genes.

Here we explore a subset of hereditary kidney disorders in order to illustrate the breadth of genes that can contribute to kidney disease when disrupted. All of which can be analyzed simultaneously with a whole genome-based test like Variantyx Unity™.

Polycystic kidney disease
Characterized by development of fluid-filled sacs (cysts) within the kidney and other organs, polycystic kidney disease occurs as two different forms: an autosomal dominant form and an autosomal recessive form. The autosomal dominant form is relatively common, estimated to affect between 1 in 5,000 to 1 in 10,000 individuals. Onset of symptoms typically begin in adulthood, although the cysts will have formed much earlier. The autosomal recessive form is less common, estimated to affect between 1 in 20,000 and 1 in 40,000 individuals. Onset of symptoms typically begins at birth or in early infancy. Genes affected include: Autosomal dominant form: PKD1, PKD2; Autosomal recessive form: PKHK1

Tuberous sclerosis
Tuberous sclerosis is characterized by development of benign tumors throughout many organs of the body including the kidneys. This relatively common disorder is estimated to affect approximately 1 in 6,000 individuals, with onset often occuring in early childhood. Genes affected include: TSC1, TSC2

Von-Hippel Lindau syndrome
Von-Hippel Lindau syndrome is another disorder characterized by development of tumors in different organs of the body including the kidneys. The tumors may be benign or cancerous, and are often accompanied by fluid-filled sacs (cysts). This less common disorder is estimated to affect 1 in 36,000 individuals and typically first presents in early adulthood. Genes affected include: VHL

Alport syndrome
Characterized by progressive kidney disease along with hearing loss and eye abnormalities, this relatively rare disease affects approximately 1 in 50,000 individuals. Symptoms of Alport syndrome typically present in late childhood or early adolescence, oftentimes affecting males more severely than females. Genes affected include: COL4A3, COL4A4, COL4A5

Bartter syndrome
Bartter syndrome is a group of related kidney disorders that cause an imbalance of potassium, sodium, chloride and other molecules. There are three antenatal forms (types I, II and IV) that begin prior to birth and a less severe classic form (type III) that usually begins in early childhood. These disorders are extremely rare, believed to affect approximately 1 individual in 1,000,000 world wide. Genes affected include: Type I: SLC12A1; Type II: KCNJ1; Type III: CLCNKB; Type IV: BSND, CLCNKA, CLCNKB

Gitelman syndrome
Similar to Bartter syndrome, Gitelman syndrome is a kidney disorder that causes imbalance of molecules – in this case ions such as potassium, magnesium and calcium. The imbalance is often accompanied by painful muscle spasms and paresthesias, a tingling or prickly sensation felt on the skin. It is much less rare, affecting roughly 1 in 40,000 individuals, often first presenting symptoms in late childhood or early adolescence. Genes affected include: SLC12A3, CLCNKB

Fabry disease
Fabry disease is caused by build up of globotriaosylceramide, a type of fat, within the body’s cells, which usually leads to progressive damage to the kidneys and other organs. Most cases present in childhood, but milder forms can present later in adulthood. Fabry disease is estimated to affect from 1 in 40,000 to 1 in 60,000 males, with females less frequently, and often less severely, affected. Genes affected include: GLA

Medullary cystic kidney disease type I
This disease of rare, but unknown prevalence in characterized by fibrosis (scarring) of the kidney which impairs its function. Symptoms typically first present in adulthood. Genes affected include: MUC1

Hereditary xanthinuria
Hereditary xanthinuria is characterized by the accumulation of xanthine in multiple tissues, including the kidney where it forms crystals that can build up to form kidney stones. There are two forms, types I and II, that are distinguished by the gene affected. The combined prevalence is approximately 1 in 69,000 individuals. Genes affected include: Type I: XDH; Type II: MOCOS

Characterized by the accumulation of cystine, there are three forms of cystinosis: nephropathic, intermediate and non-nephropathic (ocular). Only the first two result in damage to the kidneys. In the case of nephropathic cystinosis, onset begins in infancy. The accumulating cystine causes renal Fanconi syndrome which affects the kidney’s ability to reabsorb certain molecules in the bloodstream and leads to nutritional imbalances and deficiencies. Intermediate cystinosis produces the same issues, but onset occurs at a later age. Cystinosis is very rare, affecting only 1 in 100,000 to 1 in 200,00 individuals, except for individuals from Brittany, France where the prevalence is approximately 1 in 26,000. Genes affected include: CTNS

Characterized by inflammation and fibrosis (scarring) of the kidney which impairs its function, nephronophthisis is the most common genetic cause of end stage renal disease in children and young adults. There are three distinct forms: juvenile, infantile and late-onset which are distinguished by the age of onset. Juvenile nephronophthisis is the most common form. Prevalence is estimated at 1 in 100,000 individuals. Genes affected include: Juvenile form: NPHP1; Infantile form: NPHP2; Late-onset form: NPHP3; others

For some disorders, treatment options are available to help delay or even completely avoid progression to end stage renal failure, making a precise diagnosis particularly valuable.



1. NIH Genetic and Rare Diseases Information Center
2. NIH Genetics Home Reference
3. HGMD Professional, version 2018.4, Qiagen

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