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Herein, we describe five new patients from four unrelated Egyptian families with complex clinical presentations including predominant neurological presentations masking the skeletal and immunological manifestations. All our patients had spasticity with variable associations of motor and mental delay or epilepsy. All except for one patient had bilateral calcification in the basal ganglia. One patient had an associated growth hormone deficiency with fair response to growth hormone therapy (GH) where the height improved from \u22123.0 SD before GH therapy to \u22122.35 SD at presentation. Patients had different forms of immune dysregulation. All patients except for one had either cellular immunodeficiency (3 patients) or combined immunodeficiency (1 patient). Whole exome sequencing was performed and revealed four <jats:italic>ACP5<\/jats:italic> variants: c.629C\u2009&gt;\u2009T (p.Ser210Phe), c.526C\u2009&gt;\u2009T (p.Arg176Ter), c.742dupC (p.Gln248ProfsTer3) and c.775G\u2009&gt;\u2009A (p.Gly259Arg). Of them, three variants were not described before. Our study reinforces the striking phenotypic variability associated with SPENCD and expands the mutational spectrum of this rare disorder. Further, it documents the positive response to growth hormone therapy in the studied patient.<\/jats:p>","DOI":"10.1007\/s00438-023-02009-1","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T10:23:20Z","timestamp":1680517400000},"page":"709-720","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Spondyloenchondrodysplasia in five new patients: identification of three novel ACP5 variants with variable neurological presentations"],"prefix":"10.1007","volume":"298","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1498-6619","authenticated-orcid":false,"given":"Rasha M.","family":"Elhossini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasnaa M.","family":"Elbendary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karima","family":"Rafat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghda M.","family":"Ghorab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed S.","family":"Abdel-Hamid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,3]]},"reference":[{"key":"2009_CR1","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/ng0211-90","volume":"43","author":"TW Behrens","year":"2011","unstructured":"Behrens TW, Graham RR (2011) TRAPing a new gene for autoimmunity. 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