CASE REPORT Open Access Clinical, genetic, and molecular characterization of hyperphosphatasia with mental retardation: a case report and literature review Layal Abi Farraj 1 , Wassim Daoud Khatoun 1 , Naji Abou Chebel 2 , Victor Wakim 1 , Katia Dawali 1 and Michella Ghassibe-Sabbagh 1* Abstract Background: Hyperphosphatasia with mental retardation syndrome (HPMRS) is a recessive disorder characterized by high blood levels of alkaline phosphatase together with typical dysmorphic signs such as cleft palate, intellectual disability, cardiac abnormalities, and developmental delay. Genes involved in the glycosylphosphatidylinositol pathway and known to be mutated in HPMRS have never been characterized in the Lebanese population. Case presentation: Herein, we describe a pair of monozygotic twins presenting with severe intellectual disability, distinct facial dysmorphism, developmental delay, and increased alkaline phosphatase level. Two individuals underwent whole exome sequencing followed by Sanger sequencing to confirm the co-segregation of the mutation in the consanguineous family. A biallelic loss of function mutation in PGAP3 was detected. Both patients were homozygous for the c.203delC (p.C68LfsX88) mutation and the parents were carriers confirming the founder effect of the mutation. High ALP serum levels confirmed the molecular diagnosis. Conclusion: Our findings have illustrated the genomic profile of PGAP3-related HPMRS which is essential for targeted molecular and genetic testing. Moreover, we found previously unreported clinical findings such as hypodontia and skin hyperpigmentation. These features, together with the novel mutation expand the phenotypic and genotypic spectrum of this rare recessive disorder. Keywords: Cleft palate, PGAP3, Lebanese population, Syndromic, HPMRS Background Orofacial clefts (OFCs) are the most common congenital craniofacial birth defects [10]. Their prevalence varies widely between populations with an average of 1/700 live births [10, 19]. OFCs arise as a result of genetic and environmental factors interfering abnormally with a set of coordinated events leading to the development of the craniofacial processes between the 4th and 8th gesta- tional weeks [6]. According to genetic and epidemio- logical risk factors, OFCs have been divided into cleft lip with or without the palate (CL/P) and cleft palate only (CPO) [9]. Clefts are known for their complex etiology and lifelong morbidity [9]. OFCs are mainly nonsyn- dromic (70% of CL/P and 50% of CPO) [9]. A large number of the genetic factors involved in the remaining 30% syndromic clefts has been identified through the ad- vancement of the genetic screening techniques [3, 8, 23]. Hyperphosphatasia with mental retardation syndrome (HPMRS) (OMIM # 239300) was first described in 1970, and was later designated as Mabry Syndrome [4, 17]. Typical facial dysmorphic signs such as cleft palate, intellectual disability, cardiac abnormalities, and brachy- telephalangy are frequently described in affected individ- uals [1, 11, 15]. Elevated serum levels of alkaline phosphatase (ALP) have been recorded in several pa- tients [1, 8]. © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. * Correspondence: michella.sabbagh@lau.edu.lb 1 Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon Full list of author information is available at the end of the article Abi Farraj et al. Diagnostic Pathology (2019) 14:123 https://doi.org/10.1186/s13000-019-0902-5