Deciphering the natural history of SCA7 in children

被引：13

作者：

Bah, M. G. ^{[1
,2
]}

Rodriguez, D. ^{[3
,4
]}

Cazeneuve, C. ^{[1
,2
]}

Mochel, F. ^{[5
]}

Devos, D. ^{[6
]}

Suppiej, A. ^{[7
,8
]}

Roubertie, A. ^{[9
,10
]}

Meunier, I ^{[9
]}

Gitiaux, C. ^{[11
]}

Curie, A. ^{[12
]}

Klapczynski, F. ^{[13
]}

Allani-Essid, N. ^{[14
]}

Carneiro, M. ^{[12
]}

Van Minkelen, R. ^{[15
]}

Kievit, A. ^{[15
]}

Fluss, J. ^{[16
]}

Leheup, B. ^{[17
]}

Ratbi, L. ^{[18
]}

Heron, D. ^{[1
,2
]}

Gras, D. ^{[19
]}

Do Cao, J. ^{[19
]}

Pichard, S. ^{[19
]}

Strubi-Villaume, I ^{[20
]}

Audo, I ^{[21
,22
]}

Lesca, G. ^{[23
]}

Charles, P. ^{[1
,2
]}

Dubois, F. ^{[24
]}

Comet-Didierjean, P. ^{[10
]}

Capri, Y. ^{[25
]}

Barondiot, C. ^{[26
]}

Barathon, M. ^{[27
]}

Ewenczyk, C. ^{[1
,2
]}

Durr, A. ^{[5
]}

Mignot, C. ^{[1
,2
]}

机构：

[1] Sorbonne Univ, Grp Hosp Pitie Salpetriere, APHP, Dept Genet, Paris, France

[2] Sorbonne Univ, Grp Hosp Pitie Salpetriere, APHP, Ctr Reference Deliciences Intellectuelles Causes, Paris, France

[3] Sorbonne Univ, Hop Trousseau, AP HP, Serv Neuropediatrie, Paris, France

[4] Sorbonne Univ, Hop Trousseau, AP HP, Ctr Reference Neurogenet, Paris, France

[5] Sorbonne Univ, Univ Hosp Pitie Salpetriere, AP HP, Inserm U1127,CNRS UMR 7225,Inst Cerveau & Moelle, Paris, France

[6] Univ Lille, CHU Lille, INSERM, Lille Neurosci & Cognit,UMR S1172, Lille, France

[7] Univ Ferrara, Dept Med Sci, Paediat Sect, Ferrara, Italy

[8] Robert Hollman Fdn, Padua, Italy

[9] Inst Neurosci Montpellier, INSERM 1051, Montpellier, France

[10] CHU Montpellier, Dept Neuropediatrie, Montpellier, France

[11] Hop Necker Enfant Malade, AP HP, Serv Neuropediatrie, Paris, France

[12] Hosp Civils Lyon, Serv Neuropediatrie, Hop Femme Mere Enfant, Lyon, France

[13] CH Meaux, Serv Neurol, Meaux, Seine & Marne, France

[14] Hop Raymond Poincare, AP HP, Serv Neurol & Reanimat Pediat, Garches, France

[15] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands

[16] Hop Univ Geneve, Unite Neurol Pediat, Hop Enfants, Geneva, Switzerland

[17] CHU Nancy, Hop Enfants, Serv Genet Clin, Vanduvre Les Nancy, France

[18] Mohammed V Univ Rabat, Fac Med & Pharm, Ctr Rech Genom Pathol Humaines GENOPATH, Rabat, Morocco

[19] Hop Robert Debre, AP HP, Serv Neuropediatrie, Paris, France

[20] CHRU Lille, Pole Biochim & Biol Mol, UF Neurobiol Ctr Biol Pathol, Lille, France

[21] Sorbonne Univ, Inst Vis, CNRS, INSERM, Paris, France

[22] INSERM DGOS CIC1423, Ctr Hosp Natl Ophtalmol Quinze Vingts, Paris, France

[23] Hosp Civils Lyon, Serv Genet, Lyon, France

[24] CHU Grenoble Alpes, Hop Couple Enfant, Serv Pediat Specialite, Grenoble, France

[25] Hop Robert Debre, AP HP, Serv Genet Clin, Paris, France

[26] CEREVES Nancy Gentilly, Medipole St Jacques, Neuropediatrie Bioseren, Nancy, France

[27] Hop Simone Veil, Serv Pediatrie, Beauvais, France

来源：

EUROPEAN JOURNAL OF NEUROLOGY | 2020年 / 27卷 / 11期

关键词：

childhood onset; paediatric; polyglutamine expansion disease; spinocerebellar ataxia type 7; ATAXIA TYPE 7; DOMINANT CEREBELLAR-ATAXIA; ADCA TYPE-II; SPINOCEREBELLAR; EXPANSION; FAMILIES; MUTATION; TYPE-7; ONSET;

D O I：

10.1111/ene.14405

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background and purpose Childhood-onset autosomal dominant cerebellar ataxia type 7 (SCA7) is a severe disease which leads to premature loss of ambulation and death. Early diagnosis of SCA7 is of major importance for genetic counselling and still relies on specific genetic testing, driven by clinical expertise. However, the precise phenotype and natural history of paediatric SCA7 has not yet been fully described. Our aims were to describe the natural history of SCA7 in a large multicentric series of children of all ages, and to find correlates to variables defining this natural history. Methods We collected and analysed clinical data from 28 children with proven SCA7. All had clinical manifestations of SCA7 and either a definite number of CAG repeats inATXN7or a long expansion > 100 CAG. Results We identified four clinical presentation patterns related to age at onset. Children of all age groups had cerebellar atrophy and retinal dystrophy. Our data, combined with those in the literature, suggest that definite ranges of CAG repeats determine paediatric SCA7 subtypes. The number of CAG repeats inversely correlated to all variables of the natural history. Age at gait ataxia onset correlated accurately to age at loss of walking ability and to age at death. Conclusion SCA7 in children has four presentation patterns that are roughly correlated to the number of CAG repeats. Our depiction of the natural history of SCA7 in children may help in monitoring the effect of future therapeutic trials.

引用

页码：2267 / 2276

页数：10

共 31 条

[1] Ataxin-7 aggregation and ubiquitination in infantile SCA7 with 180 CAG repeats [J].