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Basal ganglia calcification, idiopathic, 6(IBGC6)

MedGen UID:
901404
Concept ID:
C4225335
Disease or Syndrome
Synonym: IBGC6
 
Gene (location): XPR1 (1q25.3)
 
Monarch Initiative: MONDO:0014628
OMIM®: 616413

Disease characteristics

Excerpted from the GeneReview: Primary Familial Brain Calcification
Primary familial brain calcification (PFBC) is a neurodegenerative disorder with characteristic calcium deposits in the basal ganglia and other brain areas visualized on neuroimaging. Most affected individuals are in good health during childhood and young adulthood and typically present in the fourth to fifth decade with a gradually progressive movement disorder and neuropsychiatric symptoms. The movement disorder first manifests as clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements, or muscle cramping. Neuropsychiatric symptoms, often the first or most prominent manifestations, range from mild difficulty with concentration and memory to changes in personality and/or behavior, to psychosis and dementia. Seizures of various types occur frequently, some individuals experience chronic headache and vertigo; urinary urgency or incontinence may be present. [from GeneReviews]
Authors:
Eliana Marisa Ramos  |  Joao Oliveira  |  Maria J Sobrido, et. al.   view full author information

Additional descriptions

From OMIM
Idiopathic basal ganglia calcification-6 (IBGC6) is an autosomal dominant neurodegenerative disorder characterized by adult onset of progressive neuropsychiatric and movement disorders, although some patients remain asymptomatic. Clinical features can include dystonia, parkinsonism, gait abnormalities, psychosis, dementia, and chorea. Brain imaging shows calcifications of the basal ganglia and other brain regions (summary by Legati et al., 2015). For a detailed phenotypic description and a discussion of genetic heterogeneity of IBGC, see IBGC1 (213600).  http://www.omim.org/entry/616413
From MedlinePlus Genetics
Primary familial brain calcification is a condition characterized by abnormal deposits of calcium (calcification) in blood vessels within the brain. These calcium deposits are visible only on medical imaging and typically occur in the basal ganglia, which are structures deep within the brain that help start and control movement of the body. Other brain regions may also be affected.

The main signs and symptoms of primary familial brain calcification are movement disorders and psychiatric or behavioral problems. These difficulties usually begin in mid-adulthood, and worsen over time. Most affected individuals have a group of movement abnormalities called parkinsonism, which include unusually slow movement (bradykinesia), muscle rigidity, and tremors. Other movement problems common in people with primary familial brain calcification include involuntary tensing of various muscles (dystonia), uncontrollable movements of the limbs (choreoathetosis), and an unsteady walking style (gait).

Psychiatric and behavioral problems occur in 20 to 30 percent of people with primary familial brain calcification. These problems can include difficulty concentrating, memory loss, changes in personality, a distorted view of reality (psychosis), and decline in intellectual function (dementia). Affected individuals may also have difficulty swallowing (dysphagia), impaired speech, headache, episodes of extreme dizziness (vertigo), seizures, or urinary problems.

The severity of primary familial brain calcification varies among affected individuals; some people have no symptoms related to the condition, whereas others have significant movement and psychiatric problems.  https://medlineplus.gov/genetics/condition/primary-familial-brain-calcification

Clinical features

From HPO
Depression
MedGen UID:
4229
Concept ID:
C0011581
Mental or Behavioral Dysfunction
Frequently experiencing feelings of being down, miserable, and/or hopeless; struggling to recover from these moods; having a pessimistic outlook on the future; feeling a pervasive sense of shame; having a low self-worth; experiencing thoughts of suicide and engaging in suicidal behavior.
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.
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.
Choreoathetosis
MedGen UID:
39313
Concept ID:
C0085583
Disease or Syndrome
Involuntary movements characterized by both athetosis (inability to sustain muscles in a fixed position) and chorea (widespread jerky arrhythmic movements).
Memory impairment
MedGen UID:
68579
Concept ID:
C0233794
Mental or Behavioral Dysfunction
An impairment of memory as manifested by a reduced ability to remember things such as dates and names, and increased forgetfulness.
Parkinsonian disorder
MedGen UID:
66079
Concept ID:
C0242422
Disease or Syndrome
Characteristic neurologic anomaly resulting from degeneration of dopamine-generating cells in the substantia nigra, a region of the midbrain, characterized clinically by shaking, rigidity, slowness of movement and difficulty with walking and gait.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
Palilalia
MedGen UID:
581078
Concept ID:
C0392185
Finding
Palilalia is the involuntary repetition of one's own phrases, words, or syllables 2 or more times in a row. Typically, palilalic utterances decrease in volume with the increasing number of repetitions. Sometimes, the repetitions are also uttered with an accelerating speed.
Involuntary movements
MedGen UID:
140884
Concept ID:
C0427086
Sign or Symptom
Involuntary contractions of muscle leading to involuntary movements of extremities, neck, trunk, or face.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Basal ganglia calcification
MedGen UID:
234651
Concept ID:
C1389280
Pathologic Function
The presence of calcium deposition affecting one or more structures of the basal ganglia.

Recent clinical studies

Etiology

Salamon A, Zádori D, Ujfalusi A, Szpisjak L, Lukács M, Bihari B, Szépfalusi N, Németh VL, Maróti Z, Horváth E, Balogh I, Bereczki C, Klivényi P, Kalmár T
Metab Brain Dis 2021 Oct;36(7):2131-2139. Epub 2021 Jul 21 doi: 10.1007/s11011-021-00790-9. PMID: 34287746
Kim JH, Shin YL, Yang S, Cheon CK, Cho JH, Lee BH, Kim GH, Lee JO, Seo EJ, Choi JH, Yoo HW
Clin Endocrinol (Oxf) 2015 Dec;83(6):790-6. Epub 2015 Oct 19 doi: 10.1111/cen.12944. PMID: 26384470
Nicolas G, Charbonnier C, de Lemos RR, Richard AC, Guillin O, Wallon D, Legati A, Geschwind D, Coppola G, Frebourg T, Campion D, de Oliveira JR, Hannequin D; collaborators from the French IBGC study Group
Am J Med Genet B Neuropsychiatr Genet 2015 Oct;168(7):586-94. Epub 2015 Jun 30 doi: 10.1002/ajmg.b.32336. PMID: 26129893
Goswami R, Sharma R, Sreenivas V, Gupta N, Ganapathy A, Das S
Clin Endocrinol (Oxf) 2012 Aug;77(2):200-6. doi: 10.1111/j.1365-2265.2012.04353.x. PMID: 22288727
Bhadada SK, Bhansali A, Upreti V, Subbiah S, Khandelwal N
Neurol India 2011 Jul-Aug;59(4):586-9. doi: 10.4103/0028-3886.84342. PMID: 21891938

Diagnosis

Li M, Fu Q, Xiang L, Zheng Y, Ping W, Cao Y
BMC Neurol 2022 Nov 17;22(1):438. doi: 10.1186/s12883-022-02973-y. PMID: 36397039Free PMC Article
Khan AA, AbuAlrob H, Punthakee Z, Shrayyef M, Werfalli RE, Kassem HA, Braga M, Millar A, Hussain S, Iqbal S, Khan T, Paul T, Van Uum S, Young JEM
Endocrine 2021 May;72(2):553-561. Epub 2021 Mar 2 doi: 10.1007/s12020-021-02629-w. PMID: 33655415
Mandal AKJ, Patel NB, Missouris CG
Am J Med Sci 2020 Oct;360(4):406-409. Epub 2020 May 21 doi: 10.1016/j.amjms.2020.05.023. PMID: 32593413
Kim JH, Shin YL, Yang S, Cheon CK, Cho JH, Lee BH, Kim GH, Lee JO, Seo EJ, Choi JH, Yoo HW
Clin Endocrinol (Oxf) 2015 Dec;83(6):790-6. Epub 2015 Oct 19 doi: 10.1111/cen.12944. PMID: 26384470
Bhadada SK, Bhansali A, Upreti V, Subbiah S, Khandelwal N
Neurol India 2011 Jul-Aug;59(4):586-9. doi: 10.4103/0028-3886.84342. PMID: 21891938

Therapy

Mandal AKJ, Patel NB, Missouris CG
Am J Med Sci 2020 Oct;360(4):406-409. Epub 2020 May 21 doi: 10.1016/j.amjms.2020.05.023. PMID: 32593413
Kim JH, Shin YL, Yang S, Cheon CK, Cho JH, Lee BH, Kim GH, Lee JO, Seo EJ, Choi JH, Yoo HW
Clin Endocrinol (Oxf) 2015 Dec;83(6):790-6. Epub 2015 Oct 19 doi: 10.1111/cen.12944. PMID: 26384470
Pacheco D, Travassos AR, Antunes J, Marques MS, Filipe P, Silva R
Dermatol Online J 2013 Jun 15;19(6):18569. PMID: 24011318
Bhadada SK, Bhansali A, Upreti V, Subbiah S, Khandelwal N
Neurol India 2011 Jul-Aug;59(4):586-9. doi: 10.4103/0028-3886.84342. PMID: 21891938
Matsuyama W, Takenaga S, Nakahara K, Kawabata M, Iwakiri Y, Arimura K, Osame M
Intern Med 1997 Feb;36(2):113-7. doi: 10.2169/internalmedicine.36.113. PMID: 9099593

Prognosis

Kim JH, Shin YL, Yang S, Cheon CK, Cho JH, Lee BH, Kim GH, Lee JO, Seo EJ, Choi JH, Yoo HW
Clin Endocrinol (Oxf) 2015 Dec;83(6):790-6. Epub 2015 Oct 19 doi: 10.1111/cen.12944. PMID: 26384470
Nicolas G, Charbonnier C, de Lemos RR, Richard AC, Guillin O, Wallon D, Legati A, Geschwind D, Coppola G, Frebourg T, Campion D, de Oliveira JR, Hannequin D; collaborators from the French IBGC study Group
Am J Med Genet B Neuropsychiatr Genet 2015 Oct;168(7):586-94. Epub 2015 Jun 30 doi: 10.1002/ajmg.b.32336. PMID: 26129893
Bhadada SK, Bhansali A, Upreti V, Subbiah S, Khandelwal N
Neurol India 2011 Jul-Aug;59(4):586-9. doi: 10.4103/0028-3886.84342. PMID: 21891938
Fukunaga M, Otsuka N, Ono S, Kajihara Y, Nishishita S, Nakano Y, Yamamoto I, Torizuka K, Morita R
Radiat Med 1987 Nov-Dec;5(6):187-90. PMID: 3452848

Clinical prediction guides

Khan AA, AbuAlrob H, Punthakee Z, Shrayyef M, Werfalli RE, Kassem HA, Braga M, Millar A, Hussain S, Iqbal S, Khan T, Paul T, Van Uum S, Young JEM
Endocrine 2021 May;72(2):553-561. Epub 2021 Mar 2 doi: 10.1007/s12020-021-02629-w. PMID: 33655415
Kimura T, Miura T, Aoki K, Saito S, Hondo H, Konno T, Uchiyama A, Ikeuchi T, Takahashi H, Kakita A
Neuropathology 2016 Aug;36(4):365-71. Epub 2015 Dec 4 doi: 10.1111/neup.12280. PMID: 26635128
Nicolas G, Charbonnier C, de Lemos RR, Richard AC, Guillin O, Wallon D, Legati A, Geschwind D, Coppola G, Frebourg T, Campion D, de Oliveira JR, Hannequin D; collaborators from the French IBGC study Group
Am J Med Genet B Neuropsychiatr Genet 2015 Oct;168(7):586-94. Epub 2015 Jun 30 doi: 10.1002/ajmg.b.32336. PMID: 26129893
Aggarwal S, Kailash S, Sagar R, Tripathi M, Sreenivas V, Sharma R, Gupta N, Goswami R
Eur J Endocrinol 2013 Jun;168(6):895-903. Epub 2013 May 7 doi: 10.1530/EJE-12-0946. PMID: 23482593
Le Ber I, Marié RM, Chabot B, Lalevée C, Defer GL
J Neurol Sci 2007 Jul 15;258(1-2):115-22. Epub 2007 May 3 doi: 10.1016/j.jns.2007.03.017. PMID: 17481663

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