Table 1.

Genetic etiologies of pediatric nephrocalcinosis

Disease	Gene	Gene product	Inheritance pattern	Phenotype
Bartter syndrome type 1	SLC12A1	Bumetadine-sodium-potassium-chloride cotransporter	Autosomal recessive	Polyhydramnios, prematurity, failure to thrive, constipation, dehydration, osteopenia, intellectual disability, muscle weakness, cramping, fatigue, hypercalciuria, nephrocalcinosis
Bartter syndrome type 2	KCNJ1	Renal outer-medullary potassium channel	Autosomal recessive	Polyhydramnios, prematurity, failure to thrive, constipation, dehydration, osteopenia, intellectual disability, muscle weakness, cramping, fatigue, hypercalciuria, nephrocalcinosis
Bartter syndrome type 3	CLCNKB	Voltage-gated chloride channel	Autosomal recessive	Typically less severe than types 1/2, wide variation in phenotype hypokalemia, metabolic alkalosis, hypercalciuria, nephrocalcinosis
Bartter syndrome type 4	BSND	Beta subunit for chloride channels CLCNKA and CLCNKB	Autosomal recessive	Usually antenatal presentation, failure to thrive, hypotonia, hyporeflexia, intellectual disability, motor delay, polyhydramnios, prematurity, sensorineural hearing loss, nephrocalcinosis
Bartter syndrome type 5	CASR	Calcium-sensing receptor	Autosomal dominant	Mild, usually asymptomatic hypocalcemia, nephrocalcinosis
Dent disease type 1	CLCN5	Chloride voltage-gated channel 5	X-linked recessive	Fanconi syndrome, rickets, nephrocalcinosis, nephrolithiasis
Dent disease type 2/Lowe syndrome	OCRL	Inositol polyphosphate-5-phosphatase	X-linked recessive	Oculocerebrorenal syndrome including congenital cataracts, intellectual disability, nephrolithiasis, Fanconi syndrome
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC)	CLDN16 CLDN19	Claudin 16 Claudin 19	Autosomal recessive	Hypomagnesemia, hypocalcemia, nephrocalcinosis, urolithiasis
Williams-Beuren syndrome	Continuous deletion syndrome, hemizygous deletion of 1.5–1.8 Mb on chromosome 7q11.23 Includes ELN, LIMK1, RFC2	Elastin lim domain kinase 1 replication factor C, subunit 2	Mostly sporadic Autosomal dominant	Multisystemic disorder, intellectual disability, distinctive facial features (including broad forehead, periorbital fullness, strabismus, stellate iris, flat nasal bridge, malar flattening, long smooth philtrum, pointed chin), short stature, hypertension, supravalvular aortic stenosis, arterial stenosis, friendly social personality, endocrine abnormalities (hypercalcemia, diabetes mellitus, hypothyroidism), nephrolithiasis, constipation, rectal prolapse, spasticity, hypotonia, joint laxity, contractures
Idiopathic infantile hypercalcemia	CYP24A1	25-hydroxymitamin D 24-hydrolase	Autosomal recessive	Increased sensitivity to vitamin D leading to hypercalcemia and nephrocalcinosis