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Clinical and laboratory manifestations at initial presentation and upon reactivation were recorded. Routine brain magnetic resonance imaging scans were reviewed and severity scores were calculated for different molecular types.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven (39.4%) children presented with neurological symptoms, 13 (46.4%) with developmental delays, and four with altered levels of consciousness. Lesions predominated in white matter (39.3% subcortical, 35.7% periventricular, and 7.1% central), although 25% had gray matter involvement; 78.6% of the cases presented with cerebral volume loss. Brain stem, cerebellar, and meningeal involvement were observed in 14.3%, 25%, and 7.1%, respectively. The most common mutations were in\n                      <jats:italic>UNC13D<\/jats:italic>\n                      (53.6%),\n                      <jats:italic>PRF<\/jats:italic>\n                      (21.4%),\n                      <jats:italic>RAB27A<\/jats:italic>\n                      (17.9%), and\n                      <jats:italic>STBXP2<\/jats:italic>\n                      (7.1%); of the children with these mutations, neurological symptoms were observed in 20%, 50%, 80%, and 50%, respectively. Central nervous system reactivation was more prevalent in patients with\n                      <jats:italic>RAB27A<\/jats:italic>\n                      mutations (60%). White matter changes were noted in 16.7% of\n                      <jats:italic>PRF<\/jats:italic>\n                      cases, predominantly involving central regions, whereas 80% of\n                      <jats:italic>RAB27A<\/jats:italic>\n                      cases exhibited periventricular white matter abnormalities.\n                      <jats:italic>RAB27A<\/jats:italic>\n                      mutations were associated with higher white matter severity scores, whereas\n                      <jats:italic>UNC13D<\/jats:italic>\n                      mutations had higher cerebral atrophy scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Variable imaging manifestations were observed in familial hemophagocytic lymphohistiocytosis, with white matter involvement predominating. Patients with\n                      <jats:italic>RAB27A<\/jats:italic>\n                      mutations had more frequent clinical and imaging-based neurological involvement.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00247-025-06454-5","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T08:24:37Z","timestamp":1763454277000},"page":"443-454","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and neuroimaging features of familial hemophagocytic lymphohistiocytosis"],"prefix":"10.1007","volume":"56","author":[{"given":"Mona Gamalludin","family":"Alkaphoury","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaimaa AbdelSattar","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noura Bahaa ElDien","family":"Farghal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heba Gomaa Abdelraheem","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iman Ahmed","family":"Ragab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"6454_CR1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2005.1.82","author":"G Janka","year":"2005","unstructured":"Janka G, zur Stadt U (2005) Familial and acquired hemophagocytic lymphohistiocytosis. 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