{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:14:30Z","timestamp":1789636470030,"version":"4.0.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","funder":[{"name":"Norwegian National Advisory Unit on Rare Disorders","award":["43066"],"award-info":[{"award-number":["43066"]}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:p>MSMO1 deficiency (OMIM #616834) is an ultrarare autosomal recessive disorder of distal cholesterol metabolism with only five cases reported to date. The disorder is caused by missense variants in the <jats:italic toggle=\"yes\">MSMO1<\/jats:italic> gene encoding methylsterol monooxygenase 1, leading to the accumulation of methylsterols. Clinically, MSMO1 deficiency is characterized by growth and developmental delay, often in association with congenital cataracts, microcephaly, psoriasiform dermatitis and immune dysfunction. Treatment with oral and topical cholesterol supplements and statins was reported to improve the biochemical, immunological, and cutaneous findings, supporting a potential treatment following the precision diagnosis of MSMO1 deficiency. We describe two siblings from a consanguineous family presenting with novel clinical features of polydactyly, alopecia and spasticity. Whole-exome sequencing revealed a novel, homozygous c.548A\u2005&gt;\u2005C, p.(Glu183Ala) variant. Based on previously published treatment algorithms, we initiated a modified dosage regime with systemic cholesterol supplementation, statins and bile acid along with topical application of a cholesterol\/statin formulation. This resulted in a marked improvement of psoriasiform dermatitis and some hair growth.<\/jats:p>","DOI":"10.1097\/mcd.0000000000000461","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T15:08:45Z","timestamp":1684336125000},"page":"97-105","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":6,"title":["MSMO1 deficiency: a potentially partially treatable, ultrarare neurodevelopmental disorder with psoriasiform dermatitis, alopecia and polydactyly"],"prefix":"10.1097","volume":"32","author":[{"given":"Tinatin","family":"Tkemaladze","sequence":"first","affiliation":[{"name":"Department of Molecular and Medical Genetics, Tbilisi State Medical University"},{"name":"Department of Child Neurology, M. Iashvili Children\u2019s Central Hospital, Tbilisi, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirik","family":"Bratland","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Haukeland University Hospital"},{"name":"Department of Clinical Science, University of Bergen, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kakha","family":"Bregvadze","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics, Tbilisi State Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teona","family":"Shatirishvili","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, M. Iashvili Children\u2019s Central Hospital, Tbilisi, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nino","family":"Tatishvili","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, M. Iashvili Children\u2019s Central Hospital, Tbilisi, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elene","family":"Abzianidze","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Genetics, Tbilisi State Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Houge","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Haukeland University Hospital"},{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Douzgou","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Haukeland University Hospital"},{"name":"Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"R1-20250524","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1086\/342668","article-title":"Lathosterolosis, a novel multiple-malformation\/mental retardation syndrome due to deficiency of 3\u03b2-hydroxysteroid-\u03945-desaturase.","volume":"71","author":"Brunetti-Pierri","year":"2002","journal-title":"Am J Hum Genet"},{"key":"R2-20250524","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1046\/j.1523-1747.2003.22258.x","article-title":"Basis for abnormal desquamation and permeability barrier dysfunction in RXLI.","volume":"122","author":"Elias","year":"2004","journal-title":"J Investig Dermatol"},{"key":"R3-20250524","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ajhg.2009.03.010","article-title":"DECIPHER: database of chromosomal imbalance and phenotype in humans using ensemble resources.","volume":"84","author":"Firth","year":"2009","journal-title":"Am J Hum Genet"},{"key":"R4-20250524","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/(SICI)1096-8628(19980113)75:2<145::AID-AJMG5>3.0.CO;2-S","article-title":"Clinical phenotype of desmosterolosis.","volume":"75","author":"FitzPatrick","year":"1998","journal-title":"Am J Med Genet"},{"key":"R5-20250524","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.ymgme.2017.06.013","article-title":"A rare case of sterol-C4-methyl oxidase deficiency in a young Italian male: biochemical and molecular characterization.","volume":"121","author":"Frisso","year":"2017","journal-title":"Mol Genet Metab"},{"key":"R6-20250524","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1093\/hmg\/ddg129","article-title":"Molecular mechanisms underlying limb anomalies associated with cholesterol deficiency during gestation: implications of Hedgehog signaling.","volume":"12","author":"Gofflot","year":"2003","journal-title":"Hum Mol Genet"},{"key":"R7-20250524","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/(SICI)1096-8628(20000214)90:4<328::AID-AJMG13>3.0.CO;2-F","article-title":"CHILD syndrome caused by deficiency of 3beta-hydroxysteroid-delta8, delta7-isomerase.","volume":"90","author":"Grange","year":"2000","journal-title":"Am J Med Genet"},{"key":"R8-20250524","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1172\/JCI42650","article-title":"Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay.","volume":"121","author":"He","year":"2011","journal-title":"J Clin Investig"},{"key":"R9-20250524","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.bbalip.2013.10.009","article-title":"The role of sterol-C4-methyl oxidase in epidermal biology.","volume":"1841","author":"He","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"R10-20250524","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1002\/ajmg.c.31340","article-title":"Disorders of sterol synthesis: beyond Smith-Lemli-Opitz syndrome.","volume":"160C","author":"Herman","year":"2012","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"R11-20250524","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/ejhg.2014.289","article-title":"Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes.","volume":"23","author":"Howard","year":"2015","journal-title":"Eur J Hum Genet [online]"},{"key":"R12-20250524","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold.","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature [online]"},{"key":"R13-20250524","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1159\/000511126","article-title":"New homozygous missense MSMO1 mutation in two siblings with SC4MOL deficiency presenting with psoriasiform dermatitis.","volume":"160","author":"Kalay Yildizhan","year":"2020","journal-title":"Cytogenet Genome Res"},{"key":"R14-20250524","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/ddrr.1114","article-title":"Sterol metabolism disorders and neurodevelopment-an update.","volume":"17","author":"Kanungo","year":"2013","journal-title":"Dev Disabil Res Rev"},{"key":"R15-20250524","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1002\/(SICI)1096-8628(19990319)83:3<213::AID-AJMG15>3.0.CO;2-C","article-title":"Abnormal sterol metabolism in patients with Conradi-H\u00fcnermann-Happle syndrome and sporadic lethal chondrodysplasia punctata.","volume":"83","author":"Kelley","year":"1999","journal-title":"Am J Med Genet"},{"key":"R16-20250524","doi-asserted-by":"crossref","first-page":"100336","DOI":"10.1016\/j.ebr.2019.100336","article-title":"Making the switch: from case studies to N-of-1 trials.","volume":"12","author":"Margolis","year":"2019","journal-title":"Epilepsy Behav Rep"},{"key":"R17-20250524","doi-asserted-by":"crossref","first-page":"2783","DOI":"10.1007\/s00415-015-7971-5","article-title":"Treatment of SPG5 with cholesterol-lowering drugs.","volume":"262","author":"Mignarri","year":"2015","journal-title":"J Neurol"},{"key":"R18-20250524","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41576-019-0151-1","article-title":"DNA sensing by the cGAS\u2013STING pathway in health and disease.","volume":"20","author":"Motwani","year":"2019","journal-title":"Nat Rev Genet"},{"key":"R19-20250524","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1212\/WNL.0000000000011597","article-title":"Systematic review of N-of-1 studies in rare genetic neurodevelopmental disorders: the power of 1.","volume":"96","author":"M\u00fcller","year":"2021","journal-title":"Neurology"},{"key":"R21-20250524","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1146\/annurev-genom-091212-153412","article-title":"Disorders of cholesterol metabolism and their unanticipated convergent mechanisms of disease.","volume":"15","author":"Platt","year":"2014","journal-title":"Annu Rev Genomics Hum Genet [online]"},{"key":"R22-20250524","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome.","volume":"47","author":"Rentzsch","year":"2018","journal-title":"Nucleic Acids Res [online]"},{"key":"R23-20250524","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"R24-20250524","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/ajmg.c.31347","article-title":"Treatment of Smith-Lemli-Opitz syndrome and other sterol disorders.","volume":"160C","author":"Svoboda","year":"2012","journal-title":"Am J Med Genet C Semin Med Genet"},{"key":"R25-20250524","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/s10048-022-00688-3","article-title":"Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.","volume":"23","author":"Teive","year":"2022","journal-title":"Neurogenetics"},{"key":"R26-20250524","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.clindermatol.2011.08.022","article-title":"Abnormal epidermal barrier in the pathogenesis of psoriasis.","volume":"30","author":"Wolf","year":"2012","journal-title":"Clin Dermatol"},{"key":"R27-20250524","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3389\/fendo.2018.00509","article-title":"Sterol metabolism and transport in atherosclerosis and cancer.","volume":"9","author":"Yamauchi","year":"2018","journal-title":"Front Endocrinol"}],"container-title":["Clinical Dysmorphology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/MCD.0000000000000461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T20:01:46Z","timestamp":1748116906000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/MCD.0000000000000461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,8]]},"references-count":26,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023]]}},"URL":"https:\/\/doi.org\/10.1097\/mcd.0000000000000461","relation":{},"ISSN":["0962-8827"],"issn-type":[{"value":"0962-8827","type":"print"}],"subject":[],"published":{"date-parts":[[2023,5,8]]}}}