Ataxia pancytopenia syndrome due to SAMD9L mutation presenting as demyelinating neuropathy.
Charcot-Marie-tooth disease
SAMD9L
ataxia-pancytopenia syndrome
autosomal dominant cerebellar ataxia
demyelinating neuropathy
Journal
Journal of the peripheral nervous system : JPNS
ISSN: 1529-8027
Titre abrégé: J Peripher Nerv Syst
Pays: United States
ID NLM: 9704532
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
12
05
2020
revised:
09
08
2020
accepted:
10
08
2020
pubmed:
19
8
2020
medline:
28
9
2021
entrez:
19
8
2020
Statut:
ppublish
Résumé
Ataxia pancytopenia (ATXPC) syndrome due to gain-of-function pathogenic variants in the SAMD9L gene has been described in 38 patients to date. It is characterized by variable neurological and hematological phenotypes including ataxia, pyramidal signs, cytopenias, and hematological malignancies. Peripheral neuropathy with slowing of conduction velocities has been reported in only two affected individuals. We describe a female with childhood onset neuropathy diagnosed as Charcot-Marie-Tooth disease type 1 with onset of cerebellar ataxia in her 50s. Cerebellar, pyramidal, and neuropathic features were found on examination. Additionally, she also had conjunctival telangiectasia. Nerve conduction studies confirmed a demyelinating neuropathy. MRI brain showed cerebellar atrophy with diffuse white matter hyperintensities. OCT demonstrated global thinning of the retinal nerve fiber layer (RNFL). Full blood count has always been normal. A previously described pathogenic variant in SAMD9L [c.2956C>T p.(Arg986Cys)] was identified on whole exome sequencing. This case extends the previously described phenotype to include conjunctival telangiectasia and RNFL thinning and suggests that ATXPC syndrome should be considered in the differential for inherited demyelinating neuropathies.
Substances chimiques
SAMD9L protein, human
0
Tumor Suppressor Proteins
0
Types de publication
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
433-437Informations de copyright
© 2020 Peripheral Nerve Society.
Références
Rossor AM, Carr AS, Devine H, et al. Peripheral neuropathy in complex inherited diseases: an approach to diagnosis. J Neurol Neurosurg Psychiatry. 2017;88(10):846-863.
Davidsson J, Puschmann A. SAMD9 and SAMD9L in inherited predisposition to ataxia, pancytopenia, and myeloid malignancies. Leukemia. 2018;32(5):1106-1115.
Li FP, Potter NU, Buchanan GR, Vawter G, Whang-Peng J, Rosen RB. A family with acute leukemia, hypoplastic anemia and cerebellar ataxia: association with bone marrow C-monosomy. Am J Med. 1978;65(6):933-940.
Daghistani D, Curless R, Toledano SR, Ayyar DR. Ataxia-pancytopenia and monosomy 7 syndrome. J Pediatr. 1989;115(1):108-110.
Chen DH, Below JE, Shimamura A, et al. Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L. Am J Hum Genet. 2016;98(6):1146-1158.
Tesi B, Davidsson J, Voss M, et al. Gain-of-function SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms. Blood. 2017;129(16):2266-2279.
Cheah JJC, Brown AL, Schreiber AW, et al. A novel germline SAMD9L mutation in a family with ataxia-pancytopenia syndrome and pediatric acute lymphoblastic leukemia. Haematologica. 2019;104(7):e318-e321.
Thunstrom S, Axelsson M. Leukoencephalopathia, demyelinating peripheral neuropathy and dural ectasia explained by a not formerly described de novo mutation in the SAMD9L gene, ends 27 years of investigations - a case report. BMC Neurol. 2019;19(1):89.
Gorcenco S, Komulainen-Ebrahim J, Nordborg K, et al. Ataxia-pancytopenia syndrome with SAMD9L mutations. Neurol Genet. 2017;3(5):e183.
Trujillano D, Bertoli-Avella AM, Kumar Kandaswamy K, et al. Clinical exome sequencing: results from 2819 samples reflecting 1000 families. Eur J Hum Genet. 2017;25(2):176-182.
https://www.ncbi.nlm.nih.gov/pubmed/28116331.