Schuurs-Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review.

Jair Tenorio ,Feliciano J Ramos ,Ivón Cuscó ,Juan Pié ,Irene Valenzuela ,Luis A Pérez‐Jurado ,María Pilar Méndez Perez ,Frank J Kaiser ,Alma Kuechler ,Carmen Ayuso ,Ángel Carracedo ,Beatriz Gómez ,Francisco Barros ,Sergio Ramos ,Juan Blanco Carrión ,María Palomares‐Bralo ,Sixto García‐Miñaúr ,Enrique Galán-Gómez ,Víctor Martinez-Glez ,Eduardo F Tizzano ,Marta Pacio‐Míguez ,Fermina Lopez‐Grondona ,Beatriz Morte ,Pedro Arias ,Patricia Arias ,Berta Almoguera ,Isabel Lorda‐Sánchez ,Alba Alcochea ,Fernando Santos‐Simarro ,Julián Nevado ,Pablo Lapunzina

doi:10.3390/genes12050738

Abstract

Schuurs–Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopmental disorder is a rare disorder characterized by intellectual disability, abnormal craniofacial features and congenital malformations. SHMS is an autosomal dominant hereditary disease caused by pathogenic variants in the PACS1 gene. PACS1 is a trans-Golgi-membrane traffic regulator that directs protein cargo and several viral envelope proteins. It is upregulated during human embryonic brain development and has low expression after birth. So far, only 54 patients with SHMS have been reported. In this work, we report on seven new identified SHMS individuals with the classical c.607C > T: p.Arg206Trp PACS1 pathogenic variant and review clinical and molecular aspects of all the patients reported in the literature, providing a summary of clinical findings grouped as very frequent (≥75% of patients), frequent (50–74%), infrequent (26–49%) and rare (less than ≤25%).

Highlights

Schuurs–Hoeijmakers syndrome or PACS1 Neurodevelopmental disorder (MIM#615009) is a rare autosomal dominant disease characterized by distinctive craniofacial features, intellectual disability (ID) with variable degrees of neurodevelopmental delay and congenital anomalies
Schuurs–Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopmental disorder is a rare disorder characterized by intellectual disability, abnormal craniofacial features and congenital malformations
We report on seven new identified SHMS individuals with the classical c.607C > T: p.Arg206Trp PACS1 pathogenic variant and review clinical and molecular aspects of all the patients reported in the literature, providing a summary of clinical findings grouped as very frequent (≥75% of patients), frequent (50–74%), infrequent (26–49%) and rare

Summary

Introduction

615009) is a rare autosomal dominant disease characterized by distinctive craniofacial features, intellectual disability (ID) with variable degrees of neurodevelopmental delay and congenital anomalies. It was initially reported in 2012 in two unrelated patients with remarkably similar facial features and ID [1]. Most patients had anomalies in the eyes, nose, heart, and gastrointestinal system. After this first review, further patients were reported mainly from series of patients with ID evaluated through massive paralleled sequencing studies [3,4,5,6,7,8,9,10,11,12,13,14]. About 54 patients have been reported, all of them with a striking similar facial phenotype and with pathogenic change in PACS1

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Conclusion