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Clin Genet. 2016 Apr;89(4):501-506. doi: 10.1111/cge.12688. Epub 2015 Nov 27.

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management.

Author information

1
EA4271 "Génétique des Anomalies du Développement" (GAD), Université de Bourgogne, Dijon, France.
2
Service de Pédiatrie 1, Centre Hospitalier Universitaire Dijon, Dijon, France.
3
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.
4
Hormone Laboratory, Haukeland University Hospital, Bergen, Norway.
5
KJ Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
6
CHU Dijon, Laboratoire de Génétique Moléculaire, Dijon, France.
7
Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
8
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China.
9
SW Thames Regional Genetics Service, St. George's Hospital Medical School, London, SW17 0RE, UK.
10
Paediatric Endocrine Unit, St George's Hospital, London, UK.
11
Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain.
12
Instituto de Salud Carlos III, Unit 753, Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
13
Department of Ophthalmology, Hospital Central de la Cruz Roja San Jose y Santa Adela, Madrid, Spain.
14
Puerta de Hierro, University Hospital, Madrid, Spain.
15
Department of Medicine, Bodø, Norway.
16
Department of Human Genetics, University of Frankfurt, Frankfurt, Germany.
17
Victorian Clinical genetics Services, Murdoch Childrens Research institute, Parkville, Australia.
18
Department of Paediatrics, University of Melbourne, Melbourne, Australia.
19
Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA, USA.
20
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
21
Genetic Medicine/, University of California, San Francisco, CA, USA.
22
Département de Génétique, Hôpital Necker Enfants Malades, Paris, France.
23
Service de Pédiatrie, CH Le Havre, Le Havre, France.
24
Département de Génétique et Centre de Référence "Déficiences intellectuelles de causes rares", Paris, France.
25
Service de Génétique clinique, Amiens, France.
26
Service de Pédiatrie, Bondy, France.
27
Service de Génétique clinique, Rennes, France.
28
UMR CNRS 6290 IGDR, Universitė Rennes, Rennes, France.
29
Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'interrégion Est, FHU-TRANSLAD, Dijon, France.
30
Département d'Endocrinologie, Diabétologie et Nutrition, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.
31
Institut National de la Santé et de la Recherche Médicale Unité 1060, Centre Européen pour la nutrition et la Santé, Centre de Recherche en Nutrition Humaine Rhône-Alpes, Université Claude Bernard Lyon, Pierre-Bénite, France.
32
Service d'Endocrinologie, Centre Hospitalier Universitaire Côte-de-Nacre, Caen, France.
33
Département d'Endocrinologie, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.
34
Service de pédiatrie, CH de Valencienne, Valencienne, France.
35
Centre de Référence CLAD NdF - Service de génétique clinique Guy Fontaine, CHRU de Lille - Hôpital Jeanne de Flandre, Lille, France.
36
INSERM, UMR_S938, Centre de Recherche Saint-Antoine, Paris, France.
37
UPMC Univ Paris 06, Paris, France.
38
ICAN, Institute of Cardiometabolism And Nutrition, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France.
39
AP-HP, Hôpital Saint-Antoine, Laboratoire Commun de Biologie et Génétique Moléculaires, Paris, France.
40
Centre d'Investigation Clinique-Epidémiologique Clinique/essais cliniques du CHU de Dijon, Dijon, France.
41
Department of Pediatrics, Haukeland, University Hospital, Bergen, Norway.
42
Department of Medical Genetics, University of Calgary, Calgary, Canada.
43
Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Canada.

Abstract

SHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had four or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included intrauterine growth restriction (IUGR) <10th percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended.

KEYWORDS:

PIK3R1 gene; SHORT syndrome; diabetes; insulin resistance; intrauterine growth restriction; lipoatrophy; short stature

PMID:
26497935
DOI:
10.1111/cge.12688
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