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Hypomagnesemia, seizures, and intellectual disability 2(HOMGSMR2)

MedGen UID:
1675904
Concept ID:
C5193023
Disease or Syndrome
Synonyms: HOMGSMR2; HYPOMAGNESEMIA, SEIZURES, AND IMPAIRED INTELLECTUAL DEVELOPMENT 2
 
Gene (location): ATP1A1 (1p13.1)
 
Monarch Initiative: MONDO:0020788
OMIM®: 618314

Definition

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]

Clinical features

From HPO
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Polyuria
MedGen UID:
19404
Concept ID:
C0032617
Sign or Symptom
An increased rate of urine production.
Renal potassium wasting
MedGen UID:
339499
Concept ID:
C1846348
Finding
High urine potassium in the presence of hypokalemia.
Renal magnesium wasting
MedGen UID:
1811452
Concept ID:
C5574944
Finding
High urine magnesium in the presence of hypomagnesemia.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
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.
Status epilepticus
MedGen UID:
11586
Concept ID:
C0038220
Disease or Syndrome
Status epilepticus is a type of prolonged seizure resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1). It is a condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Generalized-onset seizure
MedGen UID:
115963
Concept ID:
C0234533
Disease or Syndrome
A generalized-onset seizure is a type of seizure originating at some point within, and rapidly engaging, bilaterally distributed networks. The networks may include cortical and subcortical structures but not necessarily the entire cortex.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
Self-biting
MedGen UID:
603118
Concept ID:
C0424375
Finding
Habitual biting of one's own body.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
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.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Hypokalemia
MedGen UID:
5712
Concept ID:
C0020621
Finding
An abnormally decreased potassium concentration in the blood.
Hypomagnesemia
MedGen UID:
57481
Concept ID:
C0151723
Disease or Syndrome
An abnormally decreased magnesium concentration in the blood.

Recent clinical studies

Etiology

Bosman W, Franken GAC, de Las Heras J, Madariaga L, Barakat TS, Oostenbrink R, van Slegtenhorst M, Perdomo-Ramírez A, Claverie-Martín F, van Eerde AM, Vargas-Poussou R, Dubourg LD, González-Recio I, Martínez-Cruz LA, de Baaij JHF, Hoenderop JGJ
Sci Rep 2024 Mar 22;14(1):6917. doi: 10.1038/s41598-024-57061-7. PMID: 38519529Free PMC Article

Diagnosis

Bamhraz AA, Franken GAC, de Baaij JHF, Rodrigues A, Grady R, Deveau S, Chanchlani R
Nephron 2021;145(6):717-720. Epub 2021 Aug 19 doi: 10.1159/000518173. PMID: 34515155
Franken GAC, Müller D, Mignot C, Keren B, Lévy J, Tabet AC, Germanaud D, Tejada MI, Kroes HY, Nievelstein RAJ, Brimble E, Ruzhnikov M, Claverie-Martin F, Szczepańska M, Ćuk M, Latta F, Konrad M, Martínez-Cruz LA, Bindels RJM, Hoenderop JGJ, Schlingmann KP, de Baaij JHF
Hum Mutat 2021 Apr;42(4):473-486. Epub 2021 Mar 1 doi: 10.1002/humu.24182. PMID: 33600043Free PMC Article

Prognosis

Bosman W, Franken GAC, de Las Heras J, Madariaga L, Barakat TS, Oostenbrink R, van Slegtenhorst M, Perdomo-Ramírez A, Claverie-Martín F, van Eerde AM, Vargas-Poussou R, Dubourg LD, González-Recio I, Martínez-Cruz LA, de Baaij JHF, Hoenderop JGJ
Sci Rep 2024 Mar 22;14(1):6917. doi: 10.1038/s41598-024-57061-7. PMID: 38519529Free PMC Article

Clinical prediction guides

Bosman W, Franken GAC, de Las Heras J, Madariaga L, Barakat TS, Oostenbrink R, van Slegtenhorst M, Perdomo-Ramírez A, Claverie-Martín F, van Eerde AM, Vargas-Poussou R, Dubourg LD, González-Recio I, Martínez-Cruz LA, de Baaij JHF, Hoenderop JGJ
Sci Rep 2024 Mar 22;14(1):6917. doi: 10.1038/s41598-024-57061-7. PMID: 38519529Free PMC Article
Arjona FJ, de Baaij JH, Schlingmann KP, Lameris AL, van Wijk E, Flik G, Regele S, Korenke GC, Neophytou B, Rust S, Reintjes N, Konrad M, Bindels RJ, Hoenderop JG
PLoS Genet 2014 Apr;10(4):e1004267. Epub 2014 Apr 3 doi: 10.1371/journal.pgen.1004267. PMID: 24699222Free PMC Article
Scholl UI, Choi M, Liu T, Ramaekers VT, Häusler MG, Grimmer J, Tobe SW, Farhi A, Nelson-Williams C, Lifton RP
Proc Natl Acad Sci U S A 2009 Apr 7;106(14):5842-7. Epub 2009 Mar 16 doi: 10.1073/pnas.0901749106. PMID: 19289823Free PMC Article

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