De Ridder Willem, van Engelen Baziel, van Alfen Nens
Department of Neurology, Neuromuscular Reference Centre, University Hospital of Antwerp, Antwerp, Belgium.
Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
Am J Med Genet A. 2022 Jun;188(6):1801-1807. doi: 10.1002/ajmg.a.62714. Epub 2022 Mar 8.
This study aimed to assess the nature of peripheral nervous system (PNS) involvement in three patients with Noonan syndrome (NS) or NS with multiple lentigines (NSML) as a related RASopathy, presenting primary with intractable neuropathic pain. We studied three unrelated adult patients with severe neuropathic pain and muscle weakness of the limbs. Nerve conduction studies and needle electromyography (EMG) were performed and PNS involvement was assessed by nerve ultrasound imaging, complemented with spinal magnetic resonance imaging (MRI) for the evaluation of proximal nerve segments. Targeted whole-exome sequencing analysis was performed when the diagnosis of NS was suspected. Two patients showed a PTPN11-related dominant and one a LZTR1-related recessive NS or NSML phenotype. The nature of PNS involvement was documented using nerve ultrasound and MRI, showing generalized or multifocal thickening of nerve roots, plexuses and peripheral nerves in all three patients. Nerve imaging using ultrasound and MRI aids in further detailing the nature of neuropathic pain and nerve hypertrophy in patients with NS. This study underlines the relevance of nerve ultrasound in neuropathies and pain syndromes. A NS diagnosis should not be overlooked in longstanding, unexplained neuropathic pain syndromes, with or without muscular weakness. Nerve ultrasound studies can help raise the suspicion for this relatively prevalent inherited multisystem disorder, which is still rather unknown among neurologists, particularly when other potential syndromic features are inconspicuous.
本研究旨在评估三例努南综合征（NS）或伴多发雀斑的努南综合征（NSML，一种相关的RAS病）患者外周神经系统（PNS）受累的性质，这些患者最初表现为顽固性神经性疼痛。我们研究了三名患有严重神经性疼痛和肢体肌肉无力的成年非相关患者。进行了神经传导研究和针极肌电图（EMG）检查，并通过神经超声成像评估PNS受累情况，辅以脊柱磁共振成像（MRI）以评估近端神经节段。当怀疑为NS诊断时，进行了靶向全外显子测序分析。两名患者表现出与PTPN11相关的显性，一名表现出与LZTR1相关的隐性NS或NSML表型。使用神经超声和MRI记录了PNS受累的性质，显示所有三名患者的神经根、神经丛和周围神经均有广泛性或多灶性增厚。超声和MRI神经成像有助于进一步详细了解NS患者神经性疼痛和神经肥大的性质。本研究强调了神经超声在神经病变和疼痛综合征中的相关性。对于长期存在的、原因不明的神经性疼痛综合征，无论有无肌肉无力，均不应忽视NS诊断。神经超声研究有助于提高对这种相对常见的遗传性多系统疾病的怀疑，而神经科医生对此病仍知之甚少，尤其是当其他潜在的综合征特征不明显时。
