TY - JOUR
T1 - Clinical delineation of the PACS1-related syndrome-Report on 19 patients
AU - and DDD study
AU - Schuurs-Hoeijmakers, Janneke H.M.
AU - Landsverk, Megan L.
AU - Foulds, Nicola
AU - Kukolich, Mary K.
AU - Gavrilova, Ralitza H.
AU - Greville-Heygate, Stephanie
AU - Hanson-Kahn, Andrea
AU - Bernstein, Jonathan A.
AU - Glass, Jennifer
AU - Chitayat, David
AU - Burrow, Thomas A.
AU - Husami, Ammar
AU - Collins, Kathleen
AU - Wusik, Katie
AU - van der Aa, Nathalie
AU - Kooy, Frank
AU - Brown, Kate Tatton
AU - Gadzicki, Dorothea
AU - Kini, Usha
AU - Alvarez, Sara
AU - Fernández-Jaén, Alberto
AU - Mcgehee, Frank
AU - Selby, Katherine
AU - Tarailo-Graovac, Maja
AU - Van Allen, Margot
AU - van Karnebeek, Clara D.M.
AU - Stavropoulos, Dimitri J.
AU - Marshall, Christian R.
AU - Merico, Daniele
AU - Gregor, Anne
AU - Zweier, Christiane
AU - Hopkin, Robert J.
AU - Chu, Yoyo Wing Yiu
AU - Chung, Brian Hon Yin
AU - de Vries, Bert B.A.
AU - Devriendt, Koenraad
AU - Hurles, Matthew E.
AU - Brunner, Han G.
N1 - Publisher Copyright:
© 2016 Wiley Periodicals, Inc.
PY - 2016/3/1
Y1 - 2016/3/1
N2 - 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.
AB - 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.
KW - Case series
KW - Clinical features
KW - Intellectual disability
KW - Mutation hotspot
KW - PACS1
KW - Recurrent mutation
KW - Syndrome
UR - http://www.scopus.com/inward/record.url?scp=84959269415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959269415&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.37476
DO - 10.1002/ajmg.a.37476
M3 - Article
C2 - 26842493
AN - SCOPUS:84959269415
SN - 1552-4825
VL - 170
SP - 670
EP - 675
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 3
ER -