Original ArticlesMSMO1 deficiency: a potentially partially treatable, ultrarare neurodevelopmental disorder with psoriasiform dermatitis, alopecia and polydactylyTkemaladze, Tinatina,b; Bratland, Eirikc,d; Bregvadze, Kakhaa; Shatirishvili, Teonab; Tatishvili, Ninob; Abzianidze, Elenea; Houge, Gunnarc,e; Douzgou, Sofiac,e Author Information aDepartment of Molecular and Medical Genetics, Tbilisi State Medical University bDepartment of Child Neurology, M. Iashvili Children’s Central Hospital, Tbilisi, Georgia cDepartment of Medical Genetics, Haukeland University Hospital dDepartment of Clinical Science, University of Bergen, Bergen, Norway eDivision of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester, UK Received 5 October 2022 Accepted 4 April 2023. Correspondence to Tinatin Tkemaladze, MD, PhD, 13, 81a, Barnovi Str, Tbilisi, 0179, Georgia, Tel: +99 5599179190; e-mail: [email protected] Clinical Dysmorphology 32(3):p 97-105, July 2023. | DOI: 10.1097/MCD.0000000000000461 Buy Metrics Abstract 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 MSMO1 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 > C, 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. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.