MedGen

Cranioectodermal dysplasia (CED) is a ciliopathy with skeletal involvement (narrow thorax, shortened proximal limbs, syndactyly, polydactyly, brachydactyly), ectodermal features (widely spaced hypoplastic teeth, hypodontia, sparse hair, skin laxity, abnormal nails), joint laxity, growth deficiency, and characteristic facial features (frontal bossing, low-set simple ears, high forehead, telecanthus, epicanthal folds, full cheeks, everted lower lip). Most affected children develop nephronophthisis that often leads to end-stage kidney disease in infancy or childhood, a major cause of morbidity and mortality. Hepatic fibrosis and retinal dystrophy are also observed. Dolichocephaly, often secondary to sagittal craniosynostosis, is a primary manifestation that distinguishes CED from most other ciliopathies. Brain malformations and developmental delay may also occur. [from GeneReviews]

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis is a progressive renal disorder characterized by excessive urinary Ca(2+) and Mg(2+) excretion. There is progressive loss of kidney function, and in about 50% of cases, the need for renal replacement therapy arises as early as the second decade of life (summary by Muller et al., 2006). Amelogenesis imperfecta may also be present in some patients (Bardet et al., 2016). A similar disorder with renal magnesium wasting, renal failure, and nephrocalcinosis (HOMG5; 248190) is caused by mutations in another tight-junction gene, CLDN19 (610036), and is distinguished by the association of severe ocular involvement. For a discussion of phenotypic and genetic heterogeneity of familial hypomagnesemia, see HOMG1 (602014). [from OMIM]

Gitelman syndrome (GTLMNS) is an autosomal recessive renal tubular salt-wasting disorder characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. It is the most common renal tubular disorder among Caucasians (prevalence of 1 in 40,000). Most patients have onset of symptoms as adults, but some present in childhood. Clinical features include transient periods of muscle weakness and tetany, abdominal pains, and chondrocalcinosis (summary by Glaudemans et al., 2012). Gitelman syndrome is sometimes referred to as a mild variant of classic Bartter syndrome (607364). For a discussion of genetic heterogeneity of Bartter syndrome, see 607364. [from OMIM]

HOMG5 is an autosomal recessive disorder characterized by severe renal magnesium wasting, progressive renal failure, nephrocalcinosis, and severe visual impairment (Konrad et al., 2006). Amelogenesis imperfecta may also be present in some patients (Yamaguti et al., 2017). For a discussion of genetic heterogeneity of renal hypomagnesemia, see 602014. [from OMIM]

Autosomal dominant renal hypomagnesium wasting (HOMG2) is characterized by hypomagnesemia due to renal magnesium loss and is associated with hypocalciuria. Patients may have convulsions and muscle cramps, but they may also be asymptomatic except for the development of chondrocalcinosis at an adult age (summary by Knoers, 2009 and de Baaij et al., 2015). For a discussion of genetic heterogeneity of renal hypomagnesemia, see 602014. [from OMIM]

Hypomagnesemia, seizures, and impaired intellectual development-2 (HOMGSMR2) is characterized by generalized seizures in infancy, severe hypomagnesemia, and renal magnesium wasting. Seizures persist despite magnesium supplementation and are associated with significantly impaired intellectual development (Schlingmann et al., 2018). For a discussion of genetic heterogeneity of hypomagnesemia, seizures, and impaired intellectual development, see HOMGSMR1 (616418). [from OMIM]

High urine magnesium in the presence of hypomagnesemia. [from HPO]