HNARMD
MCID: NRP048
MIFTS: 32

Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration (HNARMD)

Categories: Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Neuropathy, Hereditary, with or Without Age-Related Macular...

MalaCards integrated aliases for Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration:

Name: Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration 56 73
Macular Degeneration, Age-Related, 3 56 73 13 71
Age-Related Macular Degeneration 3 29 6
Hnarmd 56 73
Hereditary Sensorimotor Neuropathy with Hyperelastic Skin 58
Macular Degeneration, Age-Related, Type 3 39
Armd3 73

Characteristics:

Orphanet epidemiological data:

58
hereditary sensorimotor neuropathy with hyperelastic skin
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
variable age at onset of neuropathy (range first to sixth decade)
highly variable severity and features
macular degeneration only occurs in some patients at very late age (over 70)


HPO:

31
neuropathy, hereditary, with or without age-related macular degeneration:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases


External Ids:

OMIM 56 608895
OMIM Phenotypic Series 56 PS603075
ICD10 via Orphanet 33 G60.0
Orphanet 58 ORPHA280598
UMLS 71 C1837187

Summaries for Neuropathy, Hereditary, with or Without Age-Related Macular...

UniProtKB/Swiss-Prot : 73 Macular degeneration, age-related, 3: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
Neuropathy, hereditary, with or without age-related macular degeneration: An autosomal dominant neuropathy of the Charcot-Marie-Tooth disease group, characterized by distal muscle weakness and atrophy variably affecting the lower and upper limbs. Distal sensory impairment and decreased nerve conduction velocities are present in most but not all patients. Additional variable features are age-related macular degeneration, joint hypermobility, and hyperelastic skin.

MalaCards based summary : Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration, also known as macular degeneration, age-related, 3, is related to hereditary sensorimotor neuropathy with hyperelastic skin and macular degeneration, age-related, 1. An important gene associated with Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration is FBLN5 (Fibulin 5). The drugs Bevacizumab and Angiogenesis Inhibitors have been mentioned in the context of this disorder. Affiliated tissues include skin, eye and endothelial, and related phenotypes are distal sensory impairment and decreased nerve conduction velocity

OMIM : 56 Hereditary neuropathy with or without age-related macular degeneration is a complex autosomal dominant syndrome characterized by a variable peripheral neuropathy resembling demyelinating Charcot-Marie-Tooth disease (see, e.g., CMT1A, 118220) and/or axonal CMT (see, e.g., CMT2A1, 118210) with sensorimotor impairment mainly of the distal lower extremities, or spinal CMT, also known as distal hereditary motor neuropathy (see, e.g., HMN1; 182960) with intact sensation. Age-related macular degeneration, if present, shows very late onset in the seventies or eighties. In addition, some patients may show hyperelasticity of the skin or joints. The age at onset of neuropathy and severity of the disorder is highly variable, even within families (summary by Auer-Grumbach et al., 2011). For a phenotypic description and a discussion of genetic heterogeneity of age-related macular degeneration, see 603075. (608895)

Related Diseases for Neuropathy, Hereditary, with or Without Age-Related Macular...

Diseases related to Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hereditary sensorimotor neuropathy with hyperelastic skin 13.0
2 macular degeneration, age-related, 1 10.2
3 cataract 10.1

Symptoms & Phenotypes for Neuropathy, Hereditary, with or Without Age-Related Macular...

Human phenotypes related to Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration:

31 (show all 12)
# Description HPO Frequency HPO Source Accession
1 distal sensory impairment 31 hallmark (90%) HP:0002936
2 decreased nerve conduction velocity 31 occasional (7.5%) HP:0000762
3 joint hypermobility 31 very rare (1%) HP:0001382
4 hyperextensible skin 31 very rare (1%) HP:0000974
5 distal amyotrophy 31 very rare (1%) HP:0003693
6 macular degeneration 31 very rare (1%) HP:0000608
7 distal muscle weakness 31 very rare (1%) HP:0002460
8 peripheral axonal neuropathy 31 very rare (1%) HP:0003477
9 decreased patellar reflex 31 very rare (1%) HP:0011808
10 pes cavus 31 HP:0001761
11 choroidal neovascularization 31 HP:0011506
12 drusen 31 HP:0011510

Symptoms via clinical synopsis from OMIM:

56
Skeletal Feet:
foot deformities (in some patients)

Skeletal:
joint hypermobility (in some patients)

Muscle Soft Tissue:
distal muscle weakness due to peripheral neuropathy, lower limbs more affected than upper limbs
distal muscle atrophy due to peripheral neuropathy, lower limbs more affected than upper limbs

Head And Neck Eyes:
age-related macular degeneration (in some patients)

Skin Nails Hair Skin:
hyperelastic skin (in some patients)

Neurologic Peripheral Nervous System:
peripheral neuropathy, demyelinating
distal sensory impairment (in most patients)
decreased nerve conduction velocities (in most patients)
axonal peripheral neuropathy (in some patients)

Clinical features from OMIM:

608895

Drugs & Therapeutics for Neuropathy, Hereditary, with or Without Age-Related Macular...

Drugs for Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Bevacizumab Approved, Investigational Phase 2, Phase 3 216974-75-3
2 Angiogenesis Inhibitors Phase 2, Phase 3
3 Antineoplastic Agents, Immunological Phase 2, Phase 3

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Systemic Bevacizumab (Avastin) Therapy for Exudative Neovascular Age-Related Macular Degeneration Completed NCT00531024 Phase 2, Phase 3 Bevacizumab;Sodium Chloride
2 Intravitreal Bevacizumab for Treatment of the Second Eye With Non-Arteritic Ischemic Optic Neuropathy Unknown status NCT00813059 Phase 2 Intra-vitreal injection of bevacizumab (1.25mg/0.05ml)
3 Functional, Morphological And Safety Results After Intravitreal Bevacizumab Treatment Of Neovascular Age-related Macular Degeneration - 3 Years Of Follow-up Completed NCT01027468 Bevacizumab

Search NIH Clinical Center for Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration

Genetic Tests for Neuropathy, Hereditary, with or Without Age-Related Macular...

Genetic tests related to Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration:

# Genetic test Affiliating Genes
1 Age-Related Macular Degeneration 3 29 FBLN5

Anatomical Context for Neuropathy, Hereditary, with or Without Age-Related Macular...

MalaCards organs/tissues related to Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration:

40
Skin, Eye, Endothelial

Publications for Neuropathy, Hereditary, with or Without Age-Related Macular...

Articles related to Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration:

(show all 25)
# Title Authors PMID Year
1
Czech family confirms the link between FBLN5 and Charcot-Marie-Tooth type 1 neuropathy. 56 6
23328402 2013
2
Fibulin-5 mutations link inherited neuropathies, age-related macular degeneration and hyperelastic skin. 56 6
21576112 2011
3
Missense variations in the fibulin 5 gene and age-related macular degeneration. 56 6
15269314 2004
4
CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. 6
23972322 2013
5
An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD). 6
20843825 2010
6
Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. 6
18006700 2008
7
Deletion of complement factor H-related genes CFHR1 and CFHR3 is associated with atypical hemolytic uremic syndrome. 6
17367211 2007
8
Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration. 56
17109857 2007
9
A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. 6
16998489 2006
10
Cost-effectiveness of basic vision rehabilitation (The basic VRS-effect study): study protocol for a randomised controlled trial. 61
31989690 2020
11
Clinical and angiographic characterization of choroidal neovascularization in diabetic retinopathy. 61
31984769 2020
12
Ability of MultiColor scanning laser ophthalmoscope to detect non-glaucomatous retinal nerve fiber layer defects in eyes with retinal diseases. 61
30558574 2018
13
Repeatability and Reproducibility of Superficial Macular Retinal Vessel Density Measurements Using Optical Coherence Tomography Angiography En Face Images. 61
28910435 2017
14
Visual Function in Older Eyes in Normal Macular Health: Association with Incident Early Age-Related Macular Degeneration 3 Years Later. 61
27074381 2016
15
Bilateral same-session intravitreal injections of anti-vascular endothelial growth factors. 61
25540758 2014
16
Risk of age-related macular degeneration 3 years after cataract surgery: paired eye comparisons. 61
22959104 2012
17
Retreatment with anti-vascular endothelial growth factor therapy based on changes in visual acuity after initial stabilization of neovascular age-related macular degeneration: 3-year follow-up results. 61
22414958 2012
18
Three-year follow-up of a pilot study of ranibizumab combined with proton beam irradiation as treatment for exudative age-related macular degeneration. 61
22183743 2012
19
[Classification and diagnostic criteria of age-related macular degeneration]. 61
19157028 2008
20
Pegaptanib: new drug. In macular degeneration: too many risks for too little benefit. 61
16989023 2006
21
[Evaluating the results of surgery of choroidal neovessels]. 61
9238472 1997
22
Indocyanine green dye for choroidal angiography. 61
9120865 1996
23
Argon green vs. krypton red laser photocoagulation for extrafoveal choroidal neovascularization secondary to age-related macular degeneration: 3-year results of a multicentre randomized trial. Canadian Ophthalmology Study Group. 61
8925479 1996
24
Penetrating keratoplasty for pseudophakic bullous keratopathy associated with closed-loop anterior chamber intraocular lenses. 61
2326019 1990
25
Potential acuity meter for predicting visual acuity after Nd:YAG posterior capsulotomy. 61
3754630 1986

Variations for Neuropathy, Hereditary, with or Without Age-Related Macular...

ClinVar genetic disease variations for Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration:

6 (show top 50) (show all 63) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FBLN5 NM_006329.3(FBLN5):c.1201_1202del (p.Ser401fs)deletion Pathogenic 689758 14:92336713-92336714 14:91870369-91870370
2 FBLN5 NM_006329.3(FBLN5):c.178G>C (p.Val60Leu)SNV Pathogenic 5477 rs121434299 14:92403492-92403492 14:91937148-91937148
3 FBLN5 NM_006329.3(FBLN5):c.212G>A (p.Arg71Gln)SNV Pathogenic 5478 rs121434300 14:92403458-92403458 14:91937114-91937114
4 FBLN5 NM_006329.3(FBLN5):c.259C>T (p.Pro87Ser)SNV Pathogenic 5479 rs121434301 14:92403411-92403411 14:91937067-91937067
5 FBLN5 NM_006329.3(FBLN5):c.506T>C (p.Ile169Thr)SNV Pathogenic 5480 rs28939072 14:92357678-92357678 14:91891334-91891334
6 FBLN5 NM_006329.3(FBLN5):c.1087G>A (p.Ala363Thr)SNV Pathogenic 5482 rs121434302 14:92343929-92343929 14:91877585-91877585
7 FBLN5 NM_006329.3(FBLN5):c.1235G>A (p.Gly412Glu)SNV Pathogenic 5483 rs121434303 14:92336680-92336680 14:91870336-91870336
8 FBLN5 NM_006329.3(FBLN5):c.1117C>T (p.Arg373Cys)SNV Likely pathogenic 218358 rs864309526 14:92343899-92343899 14:91877555-91877555
9 FBLN5 NM_006329.3(FBLN5):c.268G>A (p.Gly90Ser)SNV Conflicting interpretations of pathogenicity 218359 rs144288844 14:92403402-92403402 14:91937058-91937058
10 FBLN5 NM_006329.3(FBLN5):c.376G>A (p.Val126Met)SNV Conflicting interpretations of pathogenicity 218360 rs61734479 14:92403294-92403294 14:91936950-91936950
11 FBLN5 NM_006329.3(FBLN5):c.621T>C (p.Asp207=)SNV Conflicting interpretations of pathogenicity 287193 rs200178859 14:92353655-92353655 14:91887311-91887311
12 FBLN5 NM_006329.3(FBLN5):c.273G>A (p.Pro91=)SNV Conflicting interpretations of pathogenicity 887258 14:92403397-92403397 14:91937053-91937053
13 FBLN5 NM_006329.3(FBLN5):c.1191G>A (p.Thr397=)SNV Conflicting interpretations of pathogenicity 314871 rs148660796 14:92336724-92336724 14:91870380-91870380
14 FBLN5 NM_006329.3(FBLN5):c.862+12C>TSNV Conflicting interpretations of pathogenicity 314875 rs202088447 14:92349286-92349286 14:91882942-91882942
15 FBLN5 NM_006329.3(FBLN5):c.676G>A (p.Gly226Ser)SNV Conflicting interpretations of pathogenicity 314877 rs747288805 14:92353600-92353600 14:91887256-91887256
16 FBLN5 NM_006329.3(FBLN5):c.604G>A (p.Gly202Arg)SNV Conflicting interpretations of pathogenicity 21453 rs80338765 14:92357580-92357580 14:91891236-91891236
17 FBLN5 NM_006329.3(FBLN5):c.1241G>A (p.Arg414Gln)SNV Conflicting interpretations of pathogenicity 885290 14:92336674-92336674 14:91870330-91870330
18 FBLN5 NM_006329.3(FBLN5):c.989+9C>TSNV Conflicting interpretations of pathogenicity 314874 rs557362799 14:92347627-92347627 14:91881283-91881283
19 FBLN5 NM_006329.3(FBLN5):c.*648G>ASNV Conflicting interpretations of pathogenicity 314861 rs182435130 14:92335920-92335920 14:91869576-91869576
20 FBLN5 NM_006329.3(FBLN5):c.*98G>ASNV Uncertain significance 314870 rs568348723 14:92336470-92336470 14:91870126-91870126
21 FBLN5 NM_006329.3(FBLN5):c.-139C>TSNV Uncertain significance 314884 rs554315938 14:92413712-92413712 14:91947368-91947368
22 FBLN5 NM_006329.3(FBLN5):c.-389C>ASNV Uncertain significance 314887 rs886050891 14:92413962-92413962 14:91947618-91947618
23 FBLN5 NM_006329.3(FBLN5):c.-428G>CSNV Uncertain significance 314891 rs886050893 14:92414001-92414001 14:91947657-91947657
24 FBLN5 NM_006329.3(FBLN5):c.1183C>T (p.Arg395Trp)SNV Uncertain significance 417872 rs372650987 14:92343833-92343833 14:91877489-91877489
25 FBLN5 NM_006329.3(FBLN5):c.-382C>GSNV Uncertain significance 314886 rs886050890 14:92413955-92413955 14:91947611-91947611
26 FBLN5 NM_006329.3(FBLN5):c.-413C>TSNV Uncertain significance 314889 rs886050892 14:92413986-92413986 14:91947642-91947642
27 FBLN5 NM_006329.3(FBLN5):c.*775A>CSNV Uncertain significance 314859 rs886050885 14:92335793-92335793 14:91869449-91869449
28 FBLN5 NM_006329.3(FBLN5):c.*653G>ASNV Uncertain significance 314860 rs886050886 14:92335915-92335915 14:91869571-91869571
29 FBLN5 NM_006329.3(FBLN5):c.1063G>C (p.Val355Leu)SNV Uncertain significance 886192 14:92343953-92343953 14:91877609-91877609
30 FBLN5 NM_006329.3(FBLN5):c.901C>A (p.Leu301Met)SNV Uncertain significance 888450 14:92347724-92347724 14:91881380-91881380
31 FBLN5 NM_006329.3(FBLN5):c.726C>G (p.Gly242=)SNV Uncertain significance 884224 14:92353550-92353550 14:91887206-91887206
32 FBLN5 NM_006329.3(FBLN5):c.573A>G (p.Thr191=)SNV Uncertain significance 886256 14:92357611-92357611 14:91891267-91891267
33 FBLN5 NM_006329.3(FBLN5):c.336A>G (p.Ile112Met)SNV Uncertain significance 887257 14:92403334-92403334 14:91936990-91936990
34 FBLN5 NM_006329.3(FBLN5):c.*426C>TSNV Uncertain significance 887134 14:92336142-92336142 14:91869798-91869798
35 FBLN5 NM_006329.3(FBLN5):c.*419G>CSNV Uncertain significance 888397 14:92336149-92336149 14:91869805-91869805
36 FBLN5 NM_006329.3(FBLN5):c.*121C>TSNV Uncertain significance 885288 14:92336447-92336447 14:91870103-91870103
37 FBLN5 NM_006329.3(FBLN5):c.*77T>ASNV Uncertain significance 885289 14:92336491-92336491 14:91870147-91870147
38 FBLN5 NM_006329.3(FBLN5):c.1051C>T (p.Arg351Trp)SNV Uncertain significance 5481 rs28939073 14:92343965-92343965 14:91877621-91877621
39 FBLN5 NM_006329.3(FBLN5):c.251A>G (p.Tyr84Cys)SNV Uncertain significance 314880 rs886050889 14:92403419-92403419 14:91937075-91937075
40 FBLN5 NM_006329.3(FBLN5):c.-77C>GSNV Uncertain significance 884297 14:92413650-92413650 14:91947306-91947306
41 FBLN5 NM_006329.3(FBLN5):c.124+8C>ASNV Uncertain significance 888518 14:92406901-92406901 14:91940557-91940557
42 FBLN5 NM_006329.3(FBLN5):c.*458T>CSNV Uncertain significance 314865 rs886050887 14:92336110-92336110 14:91869766-91869766
43 FBLN5 NM_006329.3(FBLN5):c.*363C>TSNV Uncertain significance 314867 rs536827304 14:92336205-92336205 14:91869861-91869861
44 FBLN5 NM_006329.3(FBLN5):c.388G>A (p.Glu130Lys)SNV Uncertain significance 314879 rs886050888 14:92361408-92361408 14:91895064-91895064
45 FBLN5 NM_006329.3(FBLN5):c.620-8T>CSNV Benign/Likely benign 226639 rs147699855 14:92353664-92353664 14:91887320-91887320
46 FBLN5 NM_006329.3(FBLN5):c.-57G>ASNV Benign/Likely benign 314883 rs546827390 14:92413630-92413630 14:91947286-91947286
47 FBLN5 NM_006329.3(FBLN5):c.-411A>GSNV Benign/Likely benign 314888 rs143296045 14:92413984-92413984 14:91947640-91947640
48 FBLN5 NM_006329.3(FBLN5):c.714T>A (p.Leu238=)SNV Benign/Likely benign 314876 rs141152607 14:92353562-92353562 14:91887218-91887218
49 FBLN5 NM_006329.3(FBLN5):c.*423T>CSNV Benign/Likely benign 314866 rs17731705 14:92336145-92336145 14:91869801-91869801
50 FBLN5 NM_006329.3(FBLN5):c.1122C>T (p.Tyr374=)SNV Benign/Likely benign 314872 rs145515678 14:92343894-92343894 14:91877550-91877550

UniProtKB/Swiss-Prot genetic disease variations for Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration:

73 (show all 12)
# Symbol AA change Variation ID SNP ID
1 FBLN5 p.Val60Leu VAR_019814 rs121434299
2 FBLN5 p.Arg71Gln VAR_019815 rs121434300
3 FBLN5 p.Pro87Ser VAR_019816 rs121434301
4 FBLN5 p.Ile169Thr VAR_019817 rs28939072
5 FBLN5 p.Arg351Trp VAR_019818 rs28939073
6 FBLN5 p.Ala363Thr VAR_019819 rs121434302
7 FBLN5 p.Gly412Glu VAR_019820 rs121434303
8 FBLN5 p.Gln124Pro VAR_072389
9 FBLN5 p.Gly267Ser VAR_072393 rs149396611
10 FBLN5 p.Thr48Ile VAR_076289 rs141200859
11 FBLN5 p.Gly90Ser VAR_076290 rs144288844
12 FBLN5 p.Arg373Cys VAR_076291 rs864309526

Expression for Neuropathy, Hereditary, with or Without Age-Related Macular...

Search GEO for disease gene expression data for Neuropathy, Hereditary, with or Without Age-Related Macular Degeneration.

Pathways for Neuropathy, Hereditary, with or Without Age-Related Macular...

GO Terms for Neuropathy, Hereditary, with or Without Age-Related Macular...

Sources for Neuropathy, Hereditary, with or Without Age-Related Macular...

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