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Clinical delineation of the PACS1-related Syndrome - Report on 19 Patients

Clinical delineation of the PACS1-related Syndrome - Report on 19 Patients
Clinical delineation of the PACS1-related Syndrome - Report on 19 Patients
We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual “wavy” profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases.
pacs1, intellectual disability, syndrome, recurrent mutation, mutation hotspot, clinical features, case series
1552-4825
541-552
Schuurs-Hoeijmakers, Janneke H.M.
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Landsverk, Megan L.
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Foulds, Nicola
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Kukolich, Mary K.
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Gavrilova, Ralitza H.
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Greville-Heygate, Stephanie
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Hanson-Kahn, Andrea
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Bernstein, Jonathan A.
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Glass, Jennifer
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Chitayat, David
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Burrow, Thomas A.
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Husami, Ammar
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Collins, Kathleen
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Wusik, Katie
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van der Aa, Nathalie
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Kooy, Frank
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Brown, Kate Tatton
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Gadzicki, Dorothea
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Kini, Usha
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Alvarez, Sara
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Fernández-Jaén, Alberto
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McGehee, Frank
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Selby, Katherine
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Tarailo-Graovac, Maja
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Van Allen, Margot
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van Karnebeek, Clara D.M.
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Stavropoulos, Dimitri J.
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Marshall, Christian R.
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Merico, Daniele
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Gregor, Anne
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Zweier, Christiane
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Hopkin, Robert J.
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Chu, Yoyo Wing-Yiu
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Chung, Brian Hon-Yin
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de Vries, Bert B.A.
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Devriendt, Koenraad
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Hurles, Matthew E.
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Brunner, Han G.
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Schuurs-Hoeijmakers, Janneke H.M.
923197e9-80a9-4252-ad3b-98d0bfcd11ba
Landsverk, Megan L.
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Foulds, Nicola
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Kukolich, Mary K.
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Gavrilova, Ralitza H.
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Greville-Heygate, Stephanie
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Hanson-Kahn, Andrea
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Bernstein, Jonathan A.
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Glass, Jennifer
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Chitayat, David
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Burrow, Thomas A.
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Husami, Ammar
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Collins, Kathleen
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Wusik, Katie
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van der Aa, Nathalie
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Kooy, Frank
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Brown, Kate Tatton
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Gadzicki, Dorothea
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Kini, Usha
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Alvarez, Sara
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Fernández-Jaén, Alberto
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McGehee, Frank
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Selby, Katherine
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Tarailo-Graovac, Maja
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Van Allen, Margot
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van Karnebeek, Clara D.M.
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Stavropoulos, Dimitri J.
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Marshall, Christian R.
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Merico, Daniele
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Gregor, Anne
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Zweier, Christiane
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Hopkin, Robert J.
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Chu, Yoyo Wing-Yiu
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Chung, Brian Hon-Yin
4054d44b-8af5-4521-a2cb-636b1f8d387b
de Vries, Bert B.A.
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Devriendt, Koenraad
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Hurles, Matthew E.
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Brunner, Han G.
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Schuurs-Hoeijmakers, Janneke H.M., Landsverk, Megan L., Foulds, Nicola, Kukolich, Mary K., Gavrilova, Ralitza H., Greville-Heygate, Stephanie, Hanson-Kahn, Andrea, Bernstein, Jonathan A., Glass, Jennifer, Chitayat, David, Burrow, Thomas A., Husami, Ammar, Collins, Kathleen, Wusik, Katie, van der Aa, Nathalie, Kooy, Frank, Brown, Kate Tatton, Gadzicki, Dorothea, Kini, Usha, Alvarez, Sara, Fernández-Jaén, Alberto, McGehee, Frank, Selby, Katherine, Tarailo-Graovac, Maja, Van Allen, Margot, van Karnebeek, Clara D.M., Stavropoulos, Dimitri J., Marshall, Christian R., Merico, Daniele, Gregor, Anne, Zweier, Christiane, Hopkin, Robert J., Chu, Yoyo Wing-Yiu, Chung, Brian Hon-Yin, de Vries, Bert B.A., Devriendt, Koenraad, Hurles, Matthew E. and Brunner, Han G. (2016) Clinical delineation of the PACS1-related Syndrome - Report on 19 Patients. American Journal of Medical Genetics: Part A, 170 (3), 541-552. (doi:10.1002/ajmg.a.37476). (PMID:26842493)

Record type: Article

Abstract

We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual “wavy” profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases.

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More information

Accepted/In Press date: 22 October 2015
e-pub ahead of print date: 3 February 2016
Published date: March 2016
Keywords: pacs1, intellectual disability, syndrome, recurrent mutation, mutation hotspot, clinical features, case series
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 387113
URI: http://eprints.soton.ac.uk/id/eprint/387113
ISSN: 1552-4825
PURE UUID: 65e561dc-5ec7-4a0a-92bc-6e5a82812b96

Catalogue record

Date deposited: 09 Feb 2016 13:44
Last modified: 15 Jul 2019 20:47

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Contributors

Author: Janneke H.M. Schuurs-Hoeijmakers
Author: Megan L. Landsverk
Author: Nicola Foulds
Author: Mary K. Kukolich
Author: Ralitza H. Gavrilova
Author: Stephanie Greville-Heygate
Author: Andrea Hanson-Kahn
Author: Jonathan A. Bernstein
Author: Jennifer Glass
Author: David Chitayat
Author: Thomas A. Burrow
Author: Ammar Husami
Author: Kathleen Collins
Author: Katie Wusik
Author: Nathalie van der Aa
Author: Frank Kooy
Author: Kate Tatton Brown
Author: Dorothea Gadzicki
Author: Usha Kini
Author: Sara Alvarez
Author: Alberto Fernández-Jaén
Author: Frank McGehee
Author: Katherine Selby
Author: Maja Tarailo-Graovac
Author: Margot Van Allen
Author: Clara D.M. van Karnebeek
Author: Dimitri J. Stavropoulos
Author: Christian R. Marshall
Author: Daniele Merico
Author: Anne Gregor
Author: Christiane Zweier
Author: Robert J. Hopkin
Author: Yoyo Wing-Yiu Chu
Author: Brian Hon-Yin Chung
Author: Bert B.A. de Vries
Author: Koenraad Devriendt
Author: Matthew E. Hurles
Author: Han G. Brunner

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