. 2021 May 13;12(5):738.

doi: 10.3390/genes12050738.

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

Jair Tenorio-Castaño^{1

2

3

4}, Beatriz Morte^{1

3}, Julián Nevado^{1

3

4

5}, Víctor Martinez-Glez^{1

4

5

6}, Fernando Santos-Simarro^{1

3

4

6}, Sixto García-Miñaúr^{1

4

6}, María Palomares-Bralo^{1

3

4

5}, Marta Pacio-Míguez^{1

3

4

5}, Beatriz Gómez^{1

3}, Pedro Arias^{1

2}, Alba Alcochea⁷, Juan Carrión⁷, Patricia Arias⁷, Berta Almoguera^{1

3

8}, Fermina López-Grondona^{3

8}, Isabel Lorda-Sanchez^{1

8}, Enrique Galán-Gómez⁹, Irene Valenzuela^{4

10}, María Pilar Méndez Perez¹¹, Ivón Cuscó¹⁰, Francisco Barros^{1

12}, Juan Pié^{1

13}, Sergio Ramos^{1

2}, Feliciano J Ramos^{1

13}, Alma Kuechler¹⁴, Eduardo Tizzano^{4

10}, Carmen Ayuso^{1

3

8}, Frank J Kaiser^{14

15}, Luis A Pérez-Jurado^{1

16}, Ángel Carracedo^{1

12

17}, The ENoD-Ciberer Consortium, The Side Consortium³, Pablo Lapunzina^{1

2

3

4

6}

Affiliations

¹ CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Melchor Fernández Almagro 3, 28029 Madrid, Spain.
² Overgrowth Syndromes Laboratory, INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), 28046 Madrid, Spain.
³ The SIDE Consortium: Spanish Intellectual Disability Exome Consortium, 28046 Madrid, Spain.
⁴ Ithaca, European Reference Network, Hospital Universitario La Paz, 28046 Madrid, Spain.
⁵ Structural and Functional Genomics-INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), 28046 Madrid, Spain.
⁶ Clinical Genetics-INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), 28046 Madrid, Spain.
⁷ FEDER (Spanish Federation for Rare Diseases), Calle del Dr. Castelo 49, 28009 Madrid, Spain.
⁸ Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28046 Madrid, Spain.
⁹ Clinical Genetics, Head of the Pediatrics Service, Hospital Materno Infantil de Badajoz, Complejo Hospitalario Universitario de Badajoz, Professor of Pediatrics, Director of the Department of Biomedical Sciences, Faculty of Medicine, University of Extremadura, 06110 Plasencia, Spain.
¹⁰ Department of Clinical and Molecular Genetics, Vall d'Hebron University Hospital and Medicine Genetics Group, Vall d'Hebron Research Institute, 08002 Barcelona, Spain.
¹¹ Clinical Genetics, Hospital Materno Infantil de Badajoz, Complejo Hospitalario Universitario de Badajoz, University of Extremadura, 06006 Badajoz, Spain.
¹² Fundación Pública Galega de Medicina Xenómica, SERGAS, Instituto de Investigación Sanitaria de Santiago (IDIS), 15702 Santiago de Compostela, Spain.
¹³ Unit of Clinical Genetics, Service of Paediatrics, University Clinic Hospital' Lozano Blesa' and Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and ISS-Aragón, 50001 Zaragoza, Spain.
¹⁴ Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
¹⁵ Center for Rare Disease/Zentrum für Seltene Erkrankungen (EZSE), University Hospital Essen, 45276 Essen, Germany.
¹⁶ Genetics Unit, Universitat Pompeu Fabra, Barcelona, Spain and Institut Hospital del Mar D'Investigacions Mediques (IMIM), 08002 Barcelona, Spain.
¹⁷ Centro de Investigación en Medicina Molécula y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, 15702 Santiago de Compostela, Spain.

PMID: 34068396
PMCID: PMC8153584
DOI: 10.3390/genes12050738

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

Jair Tenorio-Castaño et al. Genes (Basel). 2021.

. 2021 May 13;12(5):738.

doi: 10.3390/genes12050738.

Authors

Affiliations

¹ CIBERER, Centro de Investigación Biomédica en Red de Enfermedades Raras, ISCIII, Melchor Fernández Almagro 3, 28029 Madrid, Spain.
² Overgrowth Syndromes Laboratory, INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), 28046 Madrid, Spain.
³ The SIDE Consortium: Spanish Intellectual Disability Exome Consortium, 28046 Madrid, Spain.
⁴ Ithaca, European Reference Network, Hospital Universitario La Paz, 28046 Madrid, Spain.
⁵ Structural and Functional Genomics-INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), 28046 Madrid, Spain.
⁶ Clinical Genetics-INGEMM, Instituto de Genética Médica y Molecular, IdiPAZ, Hospital Universitario la Paz, Universidad Autónoma de Madrid (UAM), 28046 Madrid, Spain.
⁷ FEDER (Spanish Federation for Rare Diseases), Calle del Dr. Castelo 49, 28009 Madrid, Spain.
⁸ Department of Genetics & Genomics, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28046 Madrid, Spain.
⁹ Clinical Genetics, Head of the Pediatrics Service, Hospital Materno Infantil de Badajoz, Complejo Hospitalario Universitario de Badajoz, Professor of Pediatrics, Director of the Department of Biomedical Sciences, Faculty of Medicine, University of Extremadura, 06110 Plasencia, Spain.
¹⁰ Department of Clinical and Molecular Genetics, Vall d'Hebron University Hospital and Medicine Genetics Group, Vall d'Hebron Research Institute, 08002 Barcelona, Spain.
¹¹ Clinical Genetics, Hospital Materno Infantil de Badajoz, Complejo Hospitalario Universitario de Badajoz, University of Extremadura, 06006 Badajoz, Spain.
¹² Fundación Pública Galega de Medicina Xenómica, SERGAS, Instituto de Investigación Sanitaria de Santiago (IDIS), 15702 Santiago de Compostela, Spain.
¹³ Unit of Clinical Genetics, Service of Paediatrics, University Clinic Hospital' Lozano Blesa' and Unit of Clinical Genetics and Functional Genomics, Department of Pharmacology-Physiology, School of Medicine, University of Zaragoza, CIBERER-GCV02 and ISS-Aragón, 50001 Zaragoza, Spain.
¹⁴ Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany.
¹⁵ Center for Rare Disease/Zentrum für Seltene Erkrankungen (EZSE), University Hospital Essen, 45276 Essen, Germany.
¹⁶ Genetics Unit, Universitat Pompeu Fabra, Barcelona, Spain and Institut Hospital del Mar D'Investigacions Mediques (IMIM), 08002 Barcelona, Spain.
¹⁷ Centro de Investigación en Medicina Molécula y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, 15702 Santiago de Compostela, Spain.

PMID: 34068396
PMCID: PMC8153584
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%).

Keywords: PACS1; Schuurs–Hoeijmakers syndrome; T; intellectual disability; pathogenic variant c.607C > phosphofurin acidic cluster sorting protein 1; rare disorders.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Facial phenotypes of four of the novel patients with *PACS1* pathogenic variants. (A,B) patient 1; (C,D) patient 7; (E–G) patient 4 and (I) patient 6.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Molecular Biology Databases

Research Materials

Miscellaneous