疾患詳細

疾患詳細





#260300
Parkinson disease 15, autosomal recessive (PARK15)
(Parkinsonian-pyramidal syndrome; PKPS)
(Pallidopyramidal syndrome
(Pallido-pyramidal syndrome)

パーキンソン病 15, 常染色体劣性 (PARK15)
(パーキンソン病-錐体路症候群)
(淡蒼球錐体路症候群)

責任遺伝子:605648 F-box only protein 7 (BXO7) <22q12.3>
遺伝形式:常染色体劣性

(症状)
(GARD)
 <100%>
 Parkinsonism (パーキンソニズム) [HP:0001300] [028]
 
 <30%-79%>
 Abnormal autonomic nervous system physiology (自律神経生理学的異常) [HP:0012332] [0200]
 Babinski sign (バビンスキー徴候) [HP:0003487] [0213]
 Bradykinesia (寡動) [HP:0002067] [02608]
 Dysphagia (嚥下障害) [HP:0002015] [01820]
 Dystonia (ジストニア) [HP:0001332] [0240]
 Hyperreflexia (反射亢進) [HP:0001347] [0241]
 Hypomimic face (表情減少) [HP:0000338] [0411]
 Intention tremor (企図振戦) [HP:0002080] [02610]
 Monotonic speech (単調な発語) [HP:0031435] [0235]
 Myoclonus (ミオクローヌス) [HP:0001336] [02612]
 Neurogenic bladder (神経因性膀胱) [HP:0000011] [1312]
 Postural instability (姿勢不安定) [HP:0002172] [028]
 Rigidity (固縮) [HP:0002063] [0240]
 Shuffling gait  (ひきずり歩行) [HP:0002362]  [028]
 Sleep disturbance (睡眠障害) [HP:0002360] [0152]
 Slow saccadic eye movements (遅い衝動性眼球運動) [HP:0000514] [0695]
 Spasticity (痙縮) [HP:0001257] [0241]
 Substantia nigra gliosis (黒質グリオーシス) [HP:0011960]
 Talipes equinovarus (内反尖足) [HP:0001762] [15600]
 Visual hallucinations (視覚幻覚) [HP:0002367] [0206]
 
 <5%-29%>
 Dementia (認知症) [HP:0000726] [0123]
 Lewy bodies (レビー小体) [HP:0100315] [02]
 
 
 Abnormality of extrapyramidal motor function (錐体外路運動機能異常) [HP:0002071] [02141]
 Autosomal recessive inheritance (常染色体劣性遺伝) [HP:0000007]
 Dysarthria (構音障害) [HP:0001260] [0230]
 Lower limb spasticity (下肢痙縮) [HP:0002061] [0241]
 Parkinsonism with favorable response to dopaminergic medication (ドパミンによく反応するパーキンソニズム) [HP:0002548] [028]
 Scissor gait (はさみ歩行) [HP:0012407] [028]
 Slow progression (緩徐進行性) [HP:0003677]
 Tremor (振戦) [HP:0001337] [02604]
 Young adult onset (若年成人発症) [HP:0011462]

(UR-DBMS)
【神経】錐体路症状
 痙縮, 主に下肢
 反射亢進
 はさみ歩行
 開扇反射
 錐体外路症状
 パーキンソン症状
 固縮
 動作緩慢
 Hypomimia (表情減少)
 振戦
 単調な会話
 姿勢不安定性
【四肢】内反尖足
【検査】組織は淡蒼球蒼白, ansa lenticularis 菲薄化, 黒質の軽度のしわと細胞変化, 錐体と交叉錐体路の早期脱髄を示す
【その他】思春期またはじ若年成人発症
 小児期発症が1家系で報告されている
 錐体外路症状は levodopa に反応がよい

(Responsible gene) *605648 F-box only protein 7 (BXO7) <22q12.3>
.0001 Parkinson disease 15, autosomal recessive (260300) [FBXO7, ARG378GLY] (dbSNP:rs71799110) (Shojaee et al. 2008)
.0002 Parkinson disease 15, autosomal recessive [FBXO7, ARG498TER] (dbSNP:rs121918304) (Di Fonzo et al. 2009)
.0003 Parkinson disease 15, autosomal recessive [FBXO7, IVS7DS, G-T, +1 [dbSNP:rs730880272] (Di Fonzo et al. 2009)
.0004 Parkinson disease 15, autosomal recessive [FBXO7, THR22MET] (dbSNP:rs121918305) (Di Fonzo et al. 2009)

(Note)
A number sign (#) is used with this entry because Parkinson disease-15 (PARK15), also known as the parkinsonian-pyramidal syndrome, is caused by homozygous or compound heterozygous mutation in the FBXO7 gene (605648) on chromosome 22q12.

For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see PD (168600).

Clinical Features
Davison (1954) described 5 affected cases in 3 families. In 1 family, a brother and sister with first-cousin parents were affected, and in another family, a brother and sister with uncle-niece parents were affected. The illness began in the second or early third decade with the picture of paralysis agitans and pyramidal tract signs. Postmortem examination showed pallor of the pallidal segments, thinning of the ansa lenticularis, slight shrinkage and cellular change in the substantia nigra, and early demyelination of the pyramids and crossed pyramidal tracts. One of Davison's cases had been reported by Ramsey Hunt (1917). Tremor and rigidity of 'paralysis agitans' type, parkinsonism, began at age 13. Clinically, Wilson disease was considered likely for a time. The patient survived until age 65 years. Lange and Poppe (1963) may have described the same disorder as familial progressive pallidum atrophy in 6 sibs. Lange et al. (1970) gave information on the autopsy findings.

Horowitz and Greenberg (1975) reported a brother and sister who developed parkinsonism in the first decade of life. They both later developed symptoms of cortical spinal tract disease, similar to the disorder described by Davison (1954). Clinical features included tremor, rigidity, akinesia, scissor gait, and hyperreflexia. The disorder was progressive until the institution of levodopa treatment at the ages of 18 and 20 years, respectively. The extremely favorable response of the extrapyramidal signs and the lack of equal response of the pyramidal tract signs demonstrated the specificity of the pharmacologic agent.

Livingstone (1983) described a family with affected brother and sister.

Nisipeanu et al. (1994) reported 2 unrelated consanguineous families in which 2 sibs each had levodopa-responsive parkinsonian-pyramidal syndrome. In the first family, of Libyan Jewish descent, a brother and sister both developed spasticity and hyperreflexia of the lower limbs at age 12 years. The disorder was progressive and resulted in impaired gait and later development of extrapyramidal signs, including tremor and bradykinesia. Two brothers in the second family, born of consanguineous Iraqi Jewish parents, developed lower limb spasticity at ages 21 and 23 years, respectively. Extrapyramidal signs became apparent about 3 years later. All 4 patients showed good response to levodopa treatment. Nisipeanu et al. (1994) noted that since no autopsy information was available in their patients to identify precise anatomic involvement, the term 'parkinsonian-pyramidal syndrome' would be more appropriate than 'pallido-pyramidal syndrome.'

Srivastava et al. (2005) reported a 22-year-old Indian woman, born of consanguineous parents, with a history of progressive bradykinesia and stiffness from age 12 years. From age 20, she developed blepharospasm with rapid worsening of the bradykinesia, stiffness, and postural instability confining her to bed. She also reported urinary frequency and urgency as well as ankle clonus. Physical examination showed mask-like face, monotonous speech, slow saccades, hyperreflexia, extensor plantar responses, and mild intention tremor. Cognition was normal. Brain MRI showed bilateral calcifications in the basal ganglia, which the authors suggested may be idiopathic. She had a favorable clinical response to L-DOPA.

Panagariya et al. (2007) reported a 19-year-old Indian man with an 18-month history of gradually progressive difficulty in walking, abnormal movements of the neck, and slow monotonous voice. He later developed postural tremors in both upper limbs, abnormal body posturing, and perioral dyskinesias. There was no family history of a neurologic disorder, and he had no memory impairment. Physical examination showed asymmetric pyramidal weakness and cogwheel rigidity in all 4 limbs. Single photon emission tomography (SPECT) scan revealed hypoperfusion in the left frontoparietal region and left basal ganglia and minimal hypoperfusion in left temporal lobe. He had excellent clinical response to L-DOPA.

Shojaee et al. (2008) reported a large Iranian family with parkinsonian-pyramidal syndrome. Inheritance was autosomal recessive. All affected exhibited equinovarus deformity since childhood, but pyramidal signs did not become apparent until young adulthood in the third decade of life. All exhibited Babinski signs, hyperreflexia, and spasticity restricted mainly to lower limbs. At the time of the report, only the 3 most severely affected individuals showed detectable extrapyramidal symptoms, including rigidity, bradykinesia, hypomimia, and monotone speech. These symptoms became evident 5 to 20 years after appearance of pyramidal symptoms. One patient who agreed to treatment showed favorable response to L-DOPA. None of the patients exhibited tremor, upgaze paresis, dementia, or cerebellar signs.

Di Fonzo et al. (2009) reported 2 unrelated families, of Italian and Dutch descent, respectively, with PARK15. Affected individuals had juvenile onset (range, 10 to 19 years) of progressive parkinsonism associated with spasticity, hyperreflexia, and variable response to L-DOPA. Disease progression was slow, and all patients were alive decades after symptom onset.

Mapping
Shojaee et al. (2008) performed genomewide linkage analysis of an Iranian family with parkinsonian-pyramidal syndrome using 500 K SNP arrays. The maximum parametric lod score under an autosomal recessive model was 3.39 on chromosome 22q. The authors noted that the linkage may have been missed had they used chips containing less than 100,000 SNPs across the genome.

Molecular Genetics
In affected members of an Iranian family with parkinsonian-pyramidal syndrome, Shojaee et al. (2008) identified a homozygous mutation in the FBXO7 gene (605648.0001).

In affected members of an Italian and a Dutch family with PARK15, Di Fonzo et al. (2009) identified homozygous (605648.0002) and compound heterozygous (605648.0003 and 605648.0004) mutations in the FBXO7 gene, respectively.

(文献)
(1) Hunt JR: Progressive atrophy of the globus pallidus (primary atrophy of the pallidal system): a system disease of the paralysis agitans type, characterized by atrophy of the motor cells of the corpus striatum; a contribution to the functions of the corpus striatum. Brain 40: 58-148, 1917
(2) Davison C: Pallido-pyramidal disease. J Neuropath Exp Neurol 13: 50-59, 1954
(3) Lange E, Poppe W: Klinischer Beitrag zum Krankheitsbild der progressiven Pallidumatrophie (van Bogaert). Psychiat Neurol 146: 176-192, 1963
(4) Jellinger K: Progressive Pallidumatrophie. J Neurol Sci 6: 19-44, 1968
(5) Lange, E.; Poppe, W.; Scholtze, P. :
Familial progressive pallidum atrophy. Europ. Neurol. 3: 265-267, 1970
6() Horowitz, G.; Greenberg, J. :
Pallido-pyramidal syndrome treated with levodopa. J. Neurol. Neurosurg. Psychiat. 38: 238-240, 1975
(7) Nisipeanu, P.; Kuritzky, A.; Korczyn, A. D. :
Familial levodopa-responsive parkinsonian-pyramidal syndrome Mov. Disord. 9: 673-675, 1994
(8) Srivastava, T.; Goyal, V.; Singh, S.; Shukla, G.; Behari, M. :
Pallido-pyramidal syndrome with blepharospasm and good response to levodopa. J. Neurol. 252: 1537-1538, 2005
(9) Panagariya, A.; Sharma, B.; Dev, A. :
Pallido-pyramidal syndrome: a rare entity. (Letter) Indian J. Med. Sci. 61: 156-157, 2007
(10) Shojaee, S.; Sina, F.; Banihosseini, S. S.; Kazemi, M. H.; Kalhor, R.; Shahidi, G.-A.; Fakhrai-Rad, H.; Ronaghi, M.; Elahi, E. :
Genome-wide linkage analysis of a parkinsonian-pyramidal syndrome pedigree by 500 K SNP arrays. Am. J. Hum. Genet. 82: 1375-1384, 2008
(11) Di Fonzo, A.; Dekker, M. C. J.; Montagna, P.; Baruzzi, A.; Yonova, E. H.; Correia Guedes, L.; Szczerbinska, A.; Zhao, T.; Dubbel-Hulsman, L. O. M.; Wouters, C. H.; de Graaff, E.; Oyen, W. J. G.; Simons, E. J.; Breedveld, G. J.; Oostra, B. A.; Horstink, M. W.; Bonifati, V. : FBXO7 mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome. Neurology 72: 240-245, 2009

2010/01/05
2010/11/18
2014/02/26
2016/03/01 SNP
2016/05/27 ノート改訂