Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS): new cases, systematic literature review, and associations with CSF1R-ALSP.
Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS): new cases, systematic literature review, and associations with CSF1R-ALSP.
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DOI：
10.1186/s13023-023-02772-9
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发表时间：
2023-06-22
影响因子：
3.7
通讯作者：
Wszolek, Zbigniew K.
中科院分区：
文献类型：
--
作者：
Dulski, Jaroslaw;Souza, Josiane;Santos, Mara Lucia;Wszolek, Zbigniew K.
集落刺激因子1受体（CSF1R）突变可导致常染色体显性遗传的伴有轴突球和色素性胶质细胞的CSF1R相关性白质脑病（CSF1R - ALSP），以及常染色体隐性遗传的脑部异常、神经退行性变和骨发育异常性骨硬化症（BANDDOS）。前者越来越受到关注，且已引入疾病修饰疗法；然而，关于后者的文献却很匮乏。本综述对BANDDOS进行分析，并探讨其与CSF1R - ALSP的异同。
我们系统检索并分析了先前报道的以及我们所诊治的BANDDOS病例的临床、遗传、影像学和病理学数据。我们确定了19例BANDDOS患者（根据PRISMA 2020指南进行文献检索：n = 16，我们的病例资料：n = 3）。我们发现了11种CSF1R突变，包括剪接突变（n = 3）、错义突变（n = 3）、无义突变（n = 2）、内含子突变（n = 2）以及1种框内缺失突变。所有突变均破坏了酪氨酸激酶结构域或导致无义介导的mRNA降解。资料具有异质性，所呈现的信息是指在特定症状、检查结果或所实施操作方面有足够数据的患者数量。首发症状出现在围生期（n = 5）、婴儿期（n = 2）、儿童期（n = 5）和成年期（n = 1）。17例患者中有7例存在畸形特征。神经系统症状包括言语障碍（15例中有13例）、认知能力下降（14例中有12例）、痉挛/强直（15例中有12例）、腱反射亢进（14例中有11例）、病理反射（11例中有8例）、癫痫发作（16例中有9例）、吞咽困难（12例中有9例）、发育迟缓（14例中有7例）、婴儿期肌张力减退（11例中有3例）以及视神经萎缩（7例中有2例）。17例患者中有13例观察到骨骼畸形，且属于骨发育异常性骨硬化症 - 派尔病范畴。脑部异常包括白质改变（19例中有19例）、钙化（18例中有15例）、胼胝体发育不全（16例中有12例）、脑室扩大（19例中有13例）、丹迪 - 沃克综合征（19例中有7例）以及皮质异常（10例中有4例）。3例患者在婴儿期死亡，2例在儿童期死亡，1例死亡年龄未明确。1例脑部尸检显示存在多种脑部异常，包括胼胝体缺如、小胶质细胞缺失、伴有轴突球的严重白质萎缩、胶质增生以及大量营养不良性钙化。
总之，BANDDOS在围生期或婴儿期发病，病程具有毁灭性，伴有先天性脑部异常、发育迟缓、神经功能缺损、骨质硬化和畸形特征。BANDDOS与CSF1R - ALSP在临床、影像学和神经病理学方面存在显著重叠。由于这两种疾病处于同一连续体上，因此存在将CSF1R - ALSP现有疗法应用于BANDDOS的机会之窗。
CSF1R mutations cause autosomal-dominant CSF1R-related leukoencephalopathy with axonal spheroids and pigmented glia (CSF1R-ALSP) and autosomal-recessive brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS). The former is increasingly recognized, and disease-modifying therapy was introduced; however, literature is scarce on the latter. This review analyzes BANDDOS and discusses similarities and differences with CSF1R-ALSP. We systematically retrieved and analyzed the clinical, genetic, radiological, and pathological data on the previously reported and our cases with BANDDOS. We identified 19 patients with BANDDOS (literature search according to the PRISMA 2020 guidelines: n = 16, our material: n = 3). We found 11 CSF1R mutations, including splicing (n = 3), missense (n = 3), nonsense (n = 2), and intronic (n = 2) variants and one inframe deletion. All mutations disrupted the tyrosine kinase domain or resulted in nonsense-mediated mRNA decay. The material is heterogenous, and the presented information refers to the number of patients with sufficient data on specific symptoms, results, or performed procedures. The first symptoms occurred in the perinatal period (n = 5), infancy (n = 2), childhood (n = 5), and adulthood (n = 1). Dysmorphic features were present in 7/17 cases. Neurological symptoms included speech disturbances (n = 13/15), cognitive decline (n = 12/14), spasticity/rigidity (n = 12/15), hyperactive tendon reflex (n = 11/14), pathological reflexes (n = 8/11), seizures (n = 9/16), dysphagia (n = 9/12), developmental delay (n = 7/14), infantile hypotonia (n = 3/11), and optic nerve atrophy (n = 2/7). Skeletal deformities were observed in 13/17 cases and fell within the dysosteosclerosis – Pyle disease spectrum. Brain abnormalities included white matter changes (n = 19/19), calcifications (n = 15/18), agenesis of corpus callosum (n = 12/16), ventriculomegaly (n = 13/19), Dandy-Walker complex (n = 7/19), and cortical abnormalities (n = 4/10). Three patients died in infancy, two in childhood, and one case at unspecified age. A single brain autopsy evidenced multiple brain anomalies, absence of corpus callosum, absence of microglia, severe white matter atrophy with axonal spheroids, gliosis, and numerous dystrophic calcifications. In conclusion, BANDDOS presents in the perinatal period or infancy and has a devastating course with congenital brain abnormalities, developmental delay, neurological deficits, osteopetrosis, and dysmorphic features. There is a significant overlap in the clinical, radiological, and neuropathological aspects between BANDDOS and CSF1R-ALSP. As both disorders are on the same continuum, there is a window of opportunity to apply available therapy in CSF1R-ALSP to BANDDOS.
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影响因子：
3.7
作者：
Sevin, Caroline;Barth, Magalie;Wilds, Alexandra;Afriyie, Abena;Walz, Markus;Dillon, Annamarie;Howie, Kenneth;Pang, Francis
通讯作者：
Pang, Francis
影响因子：
5.1
作者：
Konno T;Yoshida K;Mizuno T;Kawarai T;Tada M;Nozaki H;Ikeda SI;Nishizawa M;Onodera O;Wszolek ZK;Ikeuchi T
通讯作者：
Ikeuchi T
影响因子：
5.4
作者：
Dulski J;Heckman MG;White LJ;Żur-Wyrozumska K;Lund TC;Wszolek ZK
通讯作者：
Wszolek ZK
影响因子：
7.1
作者：
Sundal, Christina;Carmona, Susana;Guerreiro, Rita
通讯作者：
Guerreiro, Rita
影响因子：
8.8
作者：
Monies, Dorota;Maddirevula, Sateesh;Alkuraya, Fowzan S.
通讯作者：
Alkuraya, Fowzan S.