{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T10:41:20Z","timestamp":1764326480924,"version":"3.46.0"},"reference-count":86,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background\/Objectives: Cutaneous hypopigmentation is a common clinical sign observed in a variety of disorders. It may be congenital or acquired, localized or diffuse, and can range from benign to being associated with systemic conditions, including those affecting the central nervous system. Recognition of the key clinical features associated with each disorder is essential for accurate diagnosis and for differentiating one condition from another. Methods: PubMed, Embase, and Scopus databases were used to prepare a systematic review. Search terms were: \u201ccongenital\u201d, \u201ccutaneous\u201d, \u201clocalized\u201d, \u201cdiffuse\u201d, \u201chypopigmentation\u201d and \u201cneurological disorders\/signs\u201d. The focus was on congenital cutaneous hypopigmentation, distinguishing between localized and diffuse presentations, with emphasis on neurological involvement. Peer-reviewed articles, case series, and original studies with neurological manifestations of the disease were reviewed. Cutaneous hypopigmentation disorders associated with diffuse cerebral involvement include syndromes such as Chediak\u2013Higashi, Griscelli, Elejalde, Cross, Tietz albinism-deafness, Prader\u2013Willi, Angelman, and several congenital metabolic disorders. In contrast, the \u2018localized\u2019 group comprises syndromes such as Waardenburg, Incontinentia pigmenti, and the phacomatoses, including hypomelanosis of Ito and tuberous sclerosis complex. Results: Overlapping phenotypes and genetic heterogeneity lead to diagnostic challenges and potential errors suggesting multiple specialists. The main clinical features of each disorder are discussed, with particular attention paid to neurological signs. A practical flowchart is provided to help distinguish between \u2018diffuse\u2019 and \u2018localized\u2019 forms with neurological involvement. Conclusions: Early identification of cutaneous features, followed by comprehensive clinical and instrumental evaluation, enables timely and accurate diagnosis, ultimately improving the clinical outcomes for affected children.<\/jats:p>","DOI":"10.3390\/children12121621","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T09:56:02Z","timestamp":1764323762000},"page":"1621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Systematic Review of Cutaneous Hypopigmentation Disorder Associated with Neurologic Involvement"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5600-9560","authenticated-orcid":false,"given":"Piero","family":"Pavone","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University Hospital \u201cPoliclinico G. Rodolico\u201d, 95100 Catania, Italy"},{"name":"Institute for Biomedical Research and Innovation (IRIB), Italian National Research Council (CNR), 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4640-6677","authenticated-orcid":false,"given":"Xena Giada","family":"Pappalardo","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), Italian National Research Council (CNR), 95123 Catania, Italy"},{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95100 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Scrofani","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania, 95100 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4482-3506","authenticated-orcid":false,"given":"Raffaele","family":"Falsaperla","sequence":"additional","affiliation":[{"name":"Unit of Pediatrics and Pediatric Emergency, University Hospital Policlinico \u201cG. Rodolico\u201d, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Pizzo","sequence":"additional","affiliation":[{"name":"Postgraduate Training Program in Pediatrics, Department of Clinical and Experimental Medicine, University of Catania, 95100 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4865-0200","authenticated-orcid":false,"given":"Agata","family":"Polizzi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University Hospital \u201cPoliclinico G. Rodolico\u201d, 95100 Catania, Italy"},{"name":"Department of Educational Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4578-0066","authenticated-orcid":false,"given":"Antonio","family":"Corsello","sequence":"additional","affiliation":[{"name":"Pediatric Unit, Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy"},{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Chiara","family":"Consentino","sequence":"additional","affiliation":[{"name":"Postgraduate Training Program in Pediatrics, Department of Clinical and Experimental Medicine, University of Catania, 95100 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0713-7339","authenticated-orcid":false,"given":"Enrico","family":"Parano","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Research and Innovation (IRIB), Italian National Research Council (CNR), 95123 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2658-4249","authenticated-orcid":false,"given":"Martino","family":"Ruggieri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University Hospital \u201cPoliclinico G. Rodolico\u201d, 95100 Catania, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1016\/S0031-3955(16)38164-0","article-title":"Disorders of hypopigmentation in children","volume":"38","author":"Pinto","year":"1991","journal-title":"Pediatr. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.5114\/pdia.2013.33376","article-title":"Skin melanocytes: Biology and development","volume":"30","author":"Cichorek","year":"2013","journal-title":"Postepy Dermatol. Alergol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a017046","DOI":"10.1101\/cshperspect.a017046","article-title":"Melanocytes and their diseases","volume":"4","author":"Yamaguchi","year":"2014","journal-title":"Cold Spring Harb. Perspect. 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