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Renal hypomagnesemia 5 with ocular involvement(HOMG5)

MedGen UID:
1648449
Concept ID:
C4721891
Disease or Syndrome
Synonyms: FHHNC WITH SEVERE OCULAR INVOLVEMENT; HYPOMAGNESEMIA 5, RENAL, WITH OR WITHOUT OCULAR INVOLVEMENT; HYPOMAGNESEMIA, FAMILIAL, WITH HYPERCALCIURIA, NEPHROCALCINOSIS, AND SEVERE OCULAR INVOLVEMENT; Hypomagnesemia, Renal, with Ocular Involvement; MACULAR COLOBOMA, BILATERAL, WITH HYPERCALCIURIA
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
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).
 
Gene (location): CLDN19 (1p34.2)
 
Monarch Initiative: MONDO:0009548
OMIM®: 248190
Orphanet: ORPHA2196

Definition

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

Clinical features

From HPO
Hypercalciuria
MedGen UID:
43775
Concept ID:
C0020438
Finding
Abnormally high level of calcium in the urine.
Nephrocalcinosis
MedGen UID:
10222
Concept ID:
C0027709
Disease or Syndrome
Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
Nephrolithiasis
MedGen UID:
98227
Concept ID:
C0392525
Disease or Syndrome
The presence of calculi (stones) in the kidneys.
Chronic kidney disease
MedGen UID:
473458
Concept ID:
C1561643
Disease or Syndrome
Functional anomaly of the kidney persisting for at least three months.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
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.
Renal calcium wasting
MedGen UID:
392919
Concept ID:
C2673441
Finding
High urine calcium in the presence of hypocalcemia.
Hypermagnesiuria
MedGen UID:
392920
Concept ID:
C2673443
Finding
An increased concentration of magnesium the urine.
Renal magnesium wasting
MedGen UID:
1811452
Concept ID:
C5574944
Finding
High urine magnesium in the presence of hypomagnesemia.
Amelogenesis imperfecta
MedGen UID:
240
Concept ID:
C0002452
Congenital Abnormality
A developmental dysplasia of the dental enamel.
Hypomagnesemia
MedGen UID:
57481
Concept ID:
C0151723
Disease or Syndrome
An abnormally decreased magnesium concentration in the blood.
Abnormal circulating calcium concentration
MedGen UID:
868059
Concept ID:
C4022450
Finding
Any deviation from the normal concentration of calcium in the blood circulation.
Astigmatism
MedGen UID:
2473
Concept ID:
C0004106
Disease or Syndrome
Astigmatism (from the Greek 'a' meaning absence and 'stigma' meaning point) is a condition in which the parallel rays of light entering the eye through the refractive media are not focused on a single point. Both corneal and noncorneal factors contribute to refractive astigmatism. Corneal astigmatism is mainly the result of an aspheric anterior surface of the cornea, which can be measured readily by means of a keratometer; in a small fraction of cases (approximately 1 in 10) the effect is neutralized by the back surface. The curvature of the back surface of the cornea is not considered in most studies, because it is more difficult to measure; moreover, in the case of severe corneal astigmatism, there is evidence that both surfaces have the same configuration. Noncorneal factors are errors in the curvature of the 2 surfaces of the crystalline lens, irregularity in the refractive index of the lens, and an eccentric lens position. Since the cornea is the dominant component of the eye's refracting system, a highly astigmatic cornea is likely to result in a similarly astigmatic ocular refraction (summary by Clementi et al., 1998).
Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.\n\nNearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.\n\nFor normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.\n\nNearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.\n\nEye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
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.
Coloboma of macula
MedGen UID:
342305
Concept ID:
C1852767
Congenital Abnormality
A macular coloboma is an area of 2-6 disk diameters in which there is total or considerable chorioretinal maldevelopment, often with extasia of the underlying sclera which produces the white appearance visible ophthalmoscopically (summary by Phillips, 1970).
Rod-cone dystrophy
MedGen UID:
1632921
Concept ID:
C4551714
Disease or Syndrome
An inherited retinal disease subtype in which the rod photoreceptors appear to be more severely affected than the cone photoreceptors. Typical presentation is with nyctalopia (due to rod dysfunction) followed by loss of mid-peripheral field of vision, which gradually extends and leaves many patients with a small central island of vision due to the preservation of macular cones.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVRenal hypomagnesemia 5 with ocular involvement

Professional guidelines

PubMed

Claverie-Martín F, Vargas-Poussou R, Müller D, García-Nieto V
Eur J Hum Genet 2015 Jun;23(6):889-. Epub 2014 Sep 3 doi: 10.1038/ejhg.2014.176. PMID: 25182135Free PMC Article

Recent clinical studies

Diagnosis

Kang TS, Siegel LM
J AAPOS 2021 Oct;25(5):316-318. Epub 2021 Aug 20 doi: 10.1016/j.jaapos.2021.05.008. PMID: 34425238
Muñoz de Escalona Rojas JE, Quereda Castañeda A, García García O
Indian J Ophthalmol 2016 Sep;64(9):683-685. doi: 10.4103/0301-4738.194331. PMID: 27853022Free PMC Article
Claverie-Martín F, Vargas-Poussou R, Müller D, García-Nieto V
Eur J Hum Genet 2015 Jun;23(6):889-. Epub 2014 Sep 3 doi: 10.1038/ejhg.2014.176. PMID: 25182135Free PMC Article
Honavar SG, Shields CL, Demirci H, Shields JA
Arch Ophthalmol 2001 Jun;119(6):833-40. doi: 10.1001/archopht.119.6.833. PMID: 11405834
Benigno V, Canonica CS, Bettinelli A, von Vigier RO, Truttmann AC, Bianchetti MG
Nephrol Dial Transplant 2000 May;15(5):605-10. doi: 10.1093/ndt/15.5.605. PMID: 10809799

Prognosis

Almeida JR, Machado Gde A, dos Santos MM, Lopes Pde F, de Matos JP, Neves AC, Lugon JR
J Bras Nefrol 2014 Jul-Sep;36(3):401-5. doi: 10.5935/0101-2800.20140057. PMID: 25317625
Benigno V, Canonica CS, Bettinelli A, von Vigier RO, Truttmann AC, Bianchetti MG
Nephrol Dial Transplant 2000 May;15(5):605-10. doi: 10.1093/ndt/15.5.605. PMID: 10809799

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