Clinical delineation of the PACS1-related syndrome - Report on 19 patients

Schuurs-Hoeijmakers JHM, Landsverk ML, Foulds N, Kukolich MK, Gavrilova RH, Greville-Heygate S, Hanson-Kahn A, Bernstein JA, Glass J, Chitayat D, Burrow TA, Husami A, Collins K, Wusik K, Van Der Aa N, Kooy F, Brown KT, Gadzicki D, Kini U, Alvarez S, Fernandez-Jaen A, Mcgehee F, Selby K, Tarailo-Graovac M, Van Allen M, Van Karnebeek CDM, Stavropoulos DJ, Marshall CR, Merico D, Gregor A, Zweier C, Hopkin RJ, Chu YWY, Chung BHY, De Vries BBA, Devriendt K, Hurles ME, Brunner HG (2016)

Publication Type: Journal article, Report

Publication year: 2016

Journal

Book Volume: 170

Pages Range: 670-5

Journal Issue: 3

DOI: 10.1002/ajmg.a.37476

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.

Authors with CRIS profile

Involved external institutions

Cincinnati Children's Hospital Medical Center United States (USA) (US) University of Hong Kong (HKU) / 香港大學 Hong Kong (HK) Katholieke Universiteit Leuven (KUL) / Catholic University of Leuven Belgium (BE) Wellcome Trust Sanger Institute - Genome Research Limited United Kingdom (GB) Radboud University Nijmegen Netherlands (NL) University of South Dakota United States (USA) (US) University of Southampton United Kingdom (GB) Mayo Clinic United States (USA) (US) University Hospital Southampton NHS United Kingdom (GB) Stanford University United States (USA) (US) University of Toronto Canada (CA) Antwerp University Hospital (UZA) Belgium (BE) St George's Hospital United Kingdom (GB) MVZ Endokrinologikum Germany (DE) Oxford University Hospitals NHS Foundation Trust United Kingdom (GB) NIMGenetics Spain (ES) European University of Madrid / Universidad Europea de Madrid (UEM) Spain (ES) Cook Children's Health Care System United States (USA) (US) University of British Columbia Canada (CA) The Hospital for Sick Children (SickKids) Canada (CA)

How to cite

APA:

Schuurs-Hoeijmakers, J.H.M., Landsverk, M.L., Foulds, N., Kukolich, M.K., Gavrilova, R.H., Greville-Heygate, S.,... Brunner, H.G. (2016). Clinical delineation of the PACS1-related syndrome - Report on 19 patients. American Journal of Medical Genetics Part A, 170(3), 670-5. https://doi.org/10.1002/ajmg.a.37476

MLA:

Schuurs-Hoeijmakers, Janneke H. M., et al. "Clinical delineation of the PACS1-related syndrome - Report on 19 patients." American Journal of Medical Genetics Part A 170.3 (2016): 670-5.

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