Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: toward recommendation for molecular testing and management.
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.
EA4271 "Génétique des Anomalies du Développement" (GAD), Université de Bourgogne, Dijon, France.|Service de Pédiatrie 1, Centre Hospitalier Universitaire Dijon, Dijon, France.
M
M
Avila
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.
D A
DA
Dyment
Hormone Laboratory, Haukeland University Hospital, Bergen, Norway.|KJ Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
J V
JV
Sagen
EA4271 "Génétique des Anomalies du Développement" (GAD), Université de Bourgogne, Dijon, France.|CHU Dijon, Laboratoire de Génétique Moléculaire, Dijon, France.
J
J
St-Onge
Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
U
U
Moog
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China.
B H Y
BHY
Chung
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong - Shenzhen Hospital, Shenzhen, China.
S
S
Mo
SW Thames Regional Genetics Service, St. George's Hospital Medical School, London, SW17 0RE, UK.
S
S
Mansour
Paediatric Endocrine Unit, St George's Hospital, London, UK.
A
A
Albanese
Institute of Medical and Molecular Genetics (INGEMM), La Paz University Hospital, Madrid, Spain.|Instituto de Salud Carlos III, Unit 753, Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
S
S
Garcia
Department of Ophthalmology, Hospital Central de la Cruz Roja San Jose y Santa Adela, Madrid, Spain.
D O
DO
Martin
Puerta de Hierro, University Hospital, Madrid, Spain.
A A
AA
Lopez
Department of Medicine, Bodø, Norway.
T
T
Claudi
Department of Human Genetics, University of Frankfurt, Frankfurt, Germany.
R
R
König
Victorian Clinical genetics Services, Murdoch Childrens Research institute, Parkville, Australia.|Department of Paediatrics, University of Melbourne, Melbourne, Australia.
S M
SM
White
Children's Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, Canada.
S L
SL
Sawyer
Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA, USA.
J A
JA
Bernstein
Division of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA, USA.
L
L
Slattery
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
R K
RK
Jobling
Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada.
G
G
Yoon
Genetic Medicine/, University of California, San Francisco, CA, USA.
C J
CJ
Curry
Département de Génétique, Hôpital Necker Enfants Malades, Paris, France.
M L
ML
Merrer
Service de Pédiatrie, CH Le Havre, Le Havre, France.
B L
BL
Luyer
Département de Génétique et Centre de Référence "Déficiences intellectuelles de causes rares", Paris, France.
D
D
Héron
Service de Génétique clinique, Amiens, France.
M
M
Mathieu-Dramard
Service de Pédiatrie, Bondy, France.
P
P
Bitoun
Service de Génétique clinique, Rennes, France.|UMR CNRS 6290 IGDR, Universitė Rennes, Rennes, France.
S
S
Odent
Département de Génétique, Hôpital Necker Enfants Malades, Paris, France.
J
J
Amiel
EA4271 "Génétique des Anomalies du Développement" (GAD), Université de Bourgogne, Dijon, France.
P
P
Kuentz
EA4271 "Génétique des Anomalies du Développement" (GAD), Université de Bourgogne, Dijon, France.|Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'interrégion Est, FHU-TRANSLAD, Dijon, France.
J
J
Thevenon
Département d'Endocrinologie, Diabétologie et Nutrition, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France.|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.
M
M
Laville
Service d'Endocrinologie, Centre Hospitalier Universitaire Côte-de-Nacre, Caen, France.
Y
Y
Reznik
Département d'Endocrinologie, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.
C
C
Fagour
Département d'Endocrinologie, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.
M-L
ML
Nunes
Service de pédiatrie, CH de Valencienne, Valencienne, France.
D
D
Delesalle
Centre de Référence CLAD NdF - Service de génétique clinique Guy Fontaine, CHRU de Lille - Hôpital Jeanne de Flandre, Lille, France.
S
S
Manouvrier
INSERM, UMR_S938, Centre de Recherche Saint-Antoine, Paris, France.|UPMC Univ Paris 06, Paris, France.|ICAN, Institute of Cardiometabolism And Nutrition, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France.|AP-HP, Hôpital Saint-Antoine, Laboratoire Commun de Biologie et Génétique Moléculaires, Paris, France.
O
O
Lascols
EA4271 "Génétique des Anomalies du Développement" (GAD), Université de Bourgogne, Dijon, France.|Service de Pédiatrie 1, Centre Hospitalier Universitaire Dijon, Dijon, France.
F
F
Huet
Centre d'Investigation Clinique-Epidémiologique Clinique/essais cliniques du CHU de Dijon, Dijon, France.
C
C
Binquet
EA4271 "Génétique des Anomalies du Développement" (GAD), Université de Bourgogne, Dijon, France.|Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'interrégion Est, FHU-TRANSLAD, Dijon, France.
L
L
Faivre
EA4271 "Génétique des Anomalies du Développement" (GAD), Université de Bourgogne, Dijon, France.|CHU Dijon, Laboratoire de Génétique Moléculaire, Dijon, France.
J-B
JB
Rivière
INSERM, UMR_S938, Centre de Recherche Saint-Antoine, Paris, France.|UPMC Univ Paris 06, Paris, France.|ICAN, Institute of Cardiometabolism And Nutrition, Groupe Hospitalier Universitaire La Pitié-Salpêtrière, Paris, France.|AP-HP, Hôpital Saint-Antoine, Laboratoire Commun de Biologie et Génétique Moléculaires, Paris, France.
C
C
Vigouroux
Department of Pediatrics, Haukeland, University Hospital, Bergen, Norway.
P R
PR
Njølstad
Department of Medical Genetics, University of Calgary, Calgary, Canada.|Alberta Children's Hospital Research Institute for Child and Maternal Health, University of Calgary, Calgary, Canada.
A M
AM
Innes
EA4271 "Génétique des Anomalies du Développement" (GAD), Université de Bourgogne, Dijon, France.|Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs de l'interrégion Est, FHU-TRANSLAD, Dijon, France.
C
C
Thauvin-Robinet
PIK3R1 gene; SHORT syndrome; diabetes; insulin resistance; intrauterine growth restriction; lipoatrophy; short stature