{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T22:37:27Z","timestamp":1778193447404,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T00:00:00Z","timestamp":1733702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>According to previous literature reports, <jats:italic>PTPN11<\/jats:italic> gene variants account for approximately 50% of Noonan syndrome (NS) cases and 85% of Leopard syndrome (LS) cases. Several patients who were diagnosed with NS or LS complicated with Chiari I malformation (CIM) and\/or syringomyelia have been reported to have a <jats:italic>PTPN11<\/jats:italic> variant. However, it is not always clear whether the association between CIM and\/or syringomyelia and <jats:italic>PTPN11<\/jats:italic> variants is real or random. We try to explain this phenomenon by reporting a clinical case and making a mini\u2010review.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively described a clinical case in detail and made a genetic test on the proband and her family members using whole\u2010exome sequencing. And made a review of the related literatures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The patient was manifesting progressive abnormal gait and muscle weakness for more than 2\u2009years before she was admitted to our hospital at the age of 5\u2009years and 2\u2009months. On examination, she looked frail and slender. She had short stature, mild intellectual disability, decreased muscle strength in the left limb, thinner left limb, left hollow foot and foot drop, weakened left knee and Achilles tendon reflexes and a positive left Babinski sign. She looked timid and had very little expressive language. MRI of the brain and spine revealed CIM and syringomyelia with hydrops. Cardiac ultrasonography revealed an ostium secundum defect. ECG examination showed no abnormalities. She received a spinal cavity subarachnoid shunt; the symptoms were relieved to some extent, and the cavity in the lumbar vertebrae was significantly reduced after the surgery. Genetic testing found a variant, c. 922A&gt;G (p. Asn308Asp) in the <jats:italic>PTPN11<\/jats:italic> gene. Both parents were wild\u2010type at this locus. A literature review found that 31 patients with NS or LS were complicated with CIM, syringomyelia or both. Together with our patient, a total of six patients in this group had the <jats:italic>PTPN11<\/jats:italic> gene variant. Among them, four were complicated with both CIM and syringomyelia, and two were complicated with CIM only.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We report another case with a <jats:italic>PTPN11<\/jats:italic> variant that was complicated with both CIM and syringomyelia. It suggests that CIM and syringomyelia may be clinical manifestations of <jats:italic>PTPN11<\/jats:italic> variation\u2010related diseases. This phenomenon may be underrated due to limitations of genetic diagnostic methods in the past. We strongly suggest routine craniocerebral and spinal MRI scans and genetic testing for patients suspected of having NS or LS.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jdn.10396","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T03:20:07Z","timestamp":1733800807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A patient with a <i>PTPN11<\/i> gene variant complicated with Chiari I malformation and syringomyelia and a review of literatures"],"prefix":"10.1002","volume":"85","author":[{"given":"Zhi","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology The Affiliated Hospital of Qingdao University  Qingdao Shandong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiao","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology The Affiliated Hospital of Qingdao University  Qingdao 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