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Neurodegeneration with brain iron accumulation 7(NBIA7)

MedGen UID:
1647672
Concept ID:
C4693583
Disease or Syndrome
Synonyms: NBIA7; NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 7
 
Gene (location): REPS1 (6q24.1)
 
Monarch Initiative: MONDO:0054763
OMIM®: 617916

Definition

Neurodegeneration with brain iron accumulation-7 (NBIA7) is characterized by iron accumulation in the basal ganglia and manifests as a progressive extrapyramidal syndrome with dystonia, rigidity, and choreoathetosis. Severity and rate of progression are variable (Drecourt et al., 2018). [from OMIM]

Clinical features

From HPO
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Dysmetria
MedGen UID:
68583
Concept ID:
C0234162
Finding
A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
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.

Recent clinical studies

Etiology

Lange LM, Gonzalez-Latapi P, Rajalingam R, Tijssen MAJ, Ebrahimi-Fakhari D, Gabbert C, Ganos C, Ghosh R, Kumar KR, Lang AE, Rossi M, van der Veen S, van de Warrenburg B, Warner T, Lohmann K, Klein C, Marras C; on behalf of the Task Force on Genetic Nomenclature in Movement Disorders
Mov Disord 2022 May;37(5):905-935. Epub 2022 Apr 28 doi: 10.1002/mds.28982. PMID: 35481685
Cozzi A, Santambrogio P, Ripamonti M, Rovida E, Levi S
Cell Mol Life Sci 2021 Apr;78(7):3355-3367. Epub 2021 Jan 13 doi: 10.1007/s00018-020-03747-w. PMID: 33439270
Dangel T, Kmieć T, Januszaniec A, Ważny B
Neurol Sci 2020 Mar;41(3):653-660. Epub 2019 Nov 22 doi: 10.1007/s10072-019-04099-5. PMID: 31758347Free PMC Article
Salomão RP, Pedroso JL, Gama MT, Dutra LA, Maciel RH, Godeiro-Junior C, Chien HF, Teive HA, Cardoso F, Barsottini OG
Arq Neuropsiquiatr 2016 Jul;74(7):587-96. doi: 10.1590/0004-282X20160080. PMID: 27487380
Morgan NV, Westaway SK, Morton JE, Gregory A, Gissen P, Sonek S, Cangul H, Coryell J, Canham N, Nardocci N, Zorzi G, Pasha S, Rodriguez D, Desguerre I, Mubaidin A, Bertini E, Trembath RC, Simonati A, Schanen C, Johnson CA, Levinson B, Woods CG, Wilmot B, Kramer P, Gitschier J, Maher ER, Hayflick SJ
Nat Genet 2006 Jul;38(7):752-4. Epub 2006 Jun 18 doi: 10.1038/ng1826. PMID: 16783378Free PMC Article

Diagnosis

Cozzi A, Santambrogio P, Ripamonti M, Rovida E, Levi S
Cell Mol Life Sci 2021 Apr;78(7):3355-3367. Epub 2021 Jan 13 doi: 10.1007/s00018-020-03747-w. PMID: 33439270
Dubbioso R, Ruggiero L, Esposito M, Tarantino P, De Angelis M, Aruta F, Pappatà S, Ugga L, Piperno A, Iorio R, Santoro L, Iodice R, Manganelli F
Neurol Sci 2020 Mar;41(3):679-685. Epub 2019 Nov 26 doi: 10.1007/s10072-019-04147-0. PMID: 31773358
Salomão RP, Pedroso JL, Gama MT, Dutra LA, Maciel RH, Godeiro-Junior C, Chien HF, Teive HA, Cardoso F, Barsottini OG
Arq Neuropsiquiatr 2016 Jul;74(7):587-96. doi: 10.1590/0004-282X20160080. PMID: 27487380
Schneider SA, Bhatia KP
Int Rev Neurobiol 2013;110:xv-xviii. doi: 10.1016/B978-0-12-410502-7.09988-9. PMID: 24209446
Liman J, Wellmer A, Rostasy K, Bähr M, Kermer P
Eur J Paediatr Neurol 2012 Mar;16(2):175-8. Epub 2011 Aug 3 doi: 10.1016/j.ejpn.2011.07.009. PMID: 21816641

Therapy

Das N, Raymick J, Sarkar S
Metab Brain Dis 2021 Oct;36(7):1627-1639. Epub 2021 Jul 27 doi: 10.1007/s11011-021-00765-w. PMID: 34313926
Bailey DK, Clark W, Kosman DJ
PLoS One 2021;16(7):e0254794. Epub 2021 Jul 26 doi: 10.1371/journal.pone.0254794. PMID: 34310628Free PMC Article
Ayton S, Portbury S, Kalinowski P, Agarwal P, Diouf I, Schneider JA, Morris MC, Bush AI
Alzheimers Dement 2021 Jul;17(7):1244-1256. Epub 2021 Jan 25 doi: 10.1002/alz.12282. PMID: 33491917Free PMC Article
Schneider SA, Bhatia KP
Int Rev Neurobiol 2013;110:xv-xviii. doi: 10.1016/B978-0-12-410502-7.09988-9. PMID: 24209446
Timmermann L, Pauls KA, Wieland K, Jech R, Kurlemann G, Sharma N, Gill SS, Haenggeli CA, Hayflick SJ, Hogarth P, Leenders KL, Limousin P, Malanga CJ, Moro E, Ostrem JL, Revilla FJ, Santens P, Schnitzler A, Tisch S, Valldeoriola F, Vesper J, Volkmann J, Woitalla D, Peker S
Brain 2010 Mar;133(Pt 3):701-12. Epub 2010 Mar 5 doi: 10.1093/brain/awq022. PMID: 20207700Free PMC Article

Prognosis

Kimura Y, Sato N, Ishiyama A, Shigemoto Y, Suzuki F, Fujii H, Maikusa N, Matsuda H, Nishioka K, Hattori N, Sasaki M
J Neuroradiol 2021 Mar;48(2):88-93. Epub 2020 Apr 23 doi: 10.1016/j.neurad.2020.04.002. PMID: 32335071
Rattay TW, Lindig T, Baets J, Smets K, Deconinck T, Söhn AS, Hörtnagel K, Eckstein KN, Wiethoff S, Reichbauer J, Döbler-Neumann M, Krägeloh-Mann I, Auer-Grumbach M, Plecko B, Münchau A, Wilken B, Janauschek M, Giese AK, De Bleecker JL, Ortibus E, Debyser M, Lopez de Munain A, Pujol A, Bassi MT, D'Angelo MG, De Jonghe P, Züchner S, Bauer P, Schöls L, Schüle R
Brain 2019 Jun 1;142(6):1561-1572. doi: 10.1093/brain/awz102. PMID: 31135052Free PMC Article
De Vloo P, Lee DJ, Dallapiazza RF, Rohani M, Fasano A, Munhoz RP, Ibrahim GM, Hodaie M, Lozano AM, Kalia SK
Mov Disord 2019 Feb;34(2):264-273. Epub 2019 Jan 11 doi: 10.1002/mds.27563. PMID: 30633810
Dezfouli MA, Alavi A, Rohani M, Rezvani M, Nekuie T, Klotzle B, Tonekaboni SH, Shahidi GA, Elahi E
Mov Disord 2013 Feb;28(2):228-32. Epub 2012 Nov 19 doi: 10.1002/mds.25271. PMID: 23166001
Timmermann L, Pauls KA, Wieland K, Jech R, Kurlemann G, Sharma N, Gill SS, Haenggeli CA, Hayflick SJ, Hogarth P, Leenders KL, Limousin P, Malanga CJ, Moro E, Ostrem JL, Revilla FJ, Santens P, Schnitzler A, Tisch S, Valldeoriola F, Vesper J, Volkmann J, Woitalla D, Peker S
Brain 2010 Mar;133(Pt 3):701-12. Epub 2010 Mar 5 doi: 10.1093/brain/awq022. PMID: 20207700Free PMC Article

Clinical prediction guides

Marchi NA, Pizzarotti B, Solelhac G, Berger M, Haba-Rubio J, Preisig M, Vollenweider P, Marques-Vidal P, Lutti A, Kherif F, Heinzer R, Draganski B
J Sleep Res 2022 Dec;31(6):e13698. Epub 2022 Jul 13 doi: 10.1111/jsr.13698. PMID: 35830960Free PMC Article
Dangel T, Kmieć T, Januszaniec A, Ważny B
Neurol Sci 2020 Mar;41(3):653-660. Epub 2019 Nov 22 doi: 10.1007/s10072-019-04099-5. PMID: 31758347Free PMC Article
Marshall RD, Collins A, Escolar ML, Jinnah HA, Klopstock T, Kruer MC, Videnovic A, Robichaux-Viehoever A, Burns C, Swett LL, Revicki DA, Bender RH, Lenderking WR
Orphanet J Rare Dis 2019 Jul 12;14(1):174. doi: 10.1186/s13023-019-1142-1. PMID: 31300018Free PMC Article
Garcia-Cazorla À, Mochel F, Lamari F, Saudubray JM
J Inherit Metab Dis 2015 Jan;38(1):19-40. Epub 2014 Nov 21 doi: 10.1007/s10545-014-9776-6. PMID: 25413954
Timmermann L, Pauls KA, Wieland K, Jech R, Kurlemann G, Sharma N, Gill SS, Haenggeli CA, Hayflick SJ, Hogarth P, Leenders KL, Limousin P, Malanga CJ, Moro E, Ostrem JL, Revilla FJ, Santens P, Schnitzler A, Tisch S, Valldeoriola F, Vesper J, Volkmann J, Woitalla D, Peker S
Brain 2010 Mar;133(Pt 3):701-12. Epub 2010 Mar 5 doi: 10.1093/brain/awq022. PMID: 20207700Free PMC Article

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