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Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region.

ABSTRACT: Congenital hypomyelinating neuropathy is a rare neonatal syndrome responsible for hypotonia and weakness. Nerve microscopic examination shows amyelination or hypomyelination. Recently, mutations in CNTNAP1 have been described in a few patients. CNTNAP1 encodes contactin-associated protein 1 (caspr-1), which is an essential component of the paranodal junctions of the peripheral and central nervous systems, and is necessary for the establishment of transverse bands that stabilize paranodal axo-glial junctions. We present the results of nerve biopsy studies of three patients from two unrelated, non-consanguineous families with compound heterozygous CNTNAP1 mutations. The lesions were identical, characterized by a hypomyelinating process; on electron microscopy, we detected, in all nodes of Ranvier, subtle lesions that have never been previously described in human nerves. Transverse bands of the myelin loops were absent, with a loss of attachment between myelin and the axolemma; elongated Schwann cell processes sometimes dissociated the Schwann cell and axon membranes that bound the space between them. These lesions were observed in the area where caspr-1 is located and are reminiscent of the lesions reported in sciatic nerves of caspr-1 null mice. CNTNAP1 mutations appear to induce characteristic ultrastructural lesions of the paranodal region.

SUBMITTER: Vallat JM

PROVIDER: S-EPMC6394372 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region.

Vallat Jean-Michel JM Nizon Mathilde M Magee Alex A Isidor Bertrand B Magy Laurent L Péréon Yann Y Richard Laurence L Ouvrier Robert R Cogné Benjamin B Devaux Jérôme J Zuchner Stephan S Mathis Stéphane S

Journal of neuropathology and experimental neurology 20161201 12

Congenital hypomyelinating neuropathy is a rare neonatal syndrome responsible for hypotonia and weakness. Nerve microscopic examination shows amyelination or hypomyelination. Recently, mutations in CNTNAP1 have been described in a few patients. CNTNAP1 encodes contactin-associated protein 1 (caspr-1), which is an essential component of the paranodal junctions of the peripheral and central nervous systems, and is necessary for the establishment of transverse bands that stabilize paranodal axo-gli ...[more]

PMID: 27818385

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Project description:ObjectiveAnti-contactin-associated protein 2 (CASPR2)-related autoimmune encephalitis (AE) is more common in adults than in children. Clinical understanding of anti-CASPR2-antibody (Ab)-related AE, diagnosis and treatment standards are lacking in children. Therefore, this retrospective study on clinical symptoms and treatment outcomes in children with anti-CASPR2-Ab-related AE was conducted, to improve the clinical understanding of the disease, its diagnosis and treatment.MethodsThis study retrospectively assessed children with anti-CASPR2-Ab-related AE from January 1, 2020, to June 30, 2022, in the Department of Neurology at Hunan Children's Hospital. Data regarding demographics, clinical symptoms, laboratory examinations, electroencephalography (EEG), imaging, and curative were collected.ResultsThirteen patients were positive for serum anti-CASPR2-Ab (age at manifestation, 25 months to 13 years old; median, 8.1 years old; male-to-female ratio, 8/5). One patient (P1) had dual Abs, including anti-CASPR2 and anti-N-methyl-D-aspartate receptor Abs; his symptoms were more severe than those of children with anti-CASPR2 Abs alone. The clinical symptoms of the 13 patients with anti-CASPR2 Ab were movement disorders (9/13), consciousness disorders (9/13), abnormal demeanor (8/13), seizures (7/13), language disorders (6/13), fever (6/13), pain (4/13), involuntary exercise (4/13), poor diet (4/13), vomiting (3/13), sleep disorders (3/13), mood disorders (3/13), eczema/itching/redness (2/13), sweating (P8), urinary disorders (P13), and cognitive disorders (P9). No tumors were found in any patient. Additionally, EEG results of six patients were abnormal and imaging findings such as abnormal signals were found in 10 patients. Moreover, all except one patient recovered well after treatment; P1 with overlapping syndrome underwent recovery for more than 2 years. None of the patients who recovered have had a relapse.Discussion and conclusionAnti-CASPR2-Ab-related AE has several clinical manifestations. Anti-CASPR2-Ab levels were higher in male patients than in female patients. Moreover, related tumors are relatively rare. Most patients benefit from immunotherapy and have a lower chance of recurrence in the short term. Furthermore, different from patients who had anti-CASPR2-Ab AE alone, those with overlapping syndrome had a severe and complex condition requiring lengthy treatment and rehabilitation. Additional studies are needed to evaluate the long-term prognosis of these patients.

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Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region.

Publications

Contactin-Associated Protein 1 (CNTNAP1) Mutations Induce Characteristic Lesions of the Paranodal Region.

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