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Clinical delineation of the PACS1 ‐related syndrome—Report on 19 patients
Author(s) -
SchuursHoeijmakers Janneke H. M.,
Landsverk Megan L.,
Foulds Nicola,
Kukolich Mary K.,
Gavrilova Ralitza H.,
GrevilleHeygate Stephanie,
HansonKahn 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,
FernándezJaén Alberto,
McGehee Frank,
Selby Katherine,
TarailoGraovac 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 WingYiu,
Chung Brian HonYin,
de Vries Bert B. A.,
Devriendt Koenraad,
Hurles Matthew E.,
Brunner Han G.
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37476
Subject(s) - hypertelorism , palpebral fissure , medicine , hypotonia , ptosis , failure to thrive , intellectual disability , dermatology , pediatrics , anatomy , surgery , psychiatry
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. © 2016 Wiley Periodicals, Inc.