Journal articles

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

Magali Avila ^{1, 2, *} David A. Dyment ³ Jørn V. Sagen ^{4, 5} Judith St-Onge ^{2, 1} Ute Moog ⁶ Brian H. Y. Chung ⁷ Sahar Mansour ⁸ Assunta Albanese ⁹ Sixto Garcia ^{10, 11} David Ortiz Martin ¹² Ainhoa Abad Lopez ¹³ Tor Claudi ¹⁴ Rainer König ^{15, 16} Susan M. White ^{17, 18} Sarah L. Sawyer ³ Jon A. Bernstein ¹⁹ Leah Slattery ¹⁹ Rebekah K. Jobling ²⁰ Grace Yoon ²⁰ Cynthia J. Curry ²¹ Martine Le Merrer ²² Bernard Le Luyer ²³ Delphine Héron ^{24, 25, 26, 27} Michèle Mathieu-Dramard ²⁸ Pierre Bitoun ²⁹ Sylvie Odent ^{30, 31} Jeanne Amiel ^{32, 22} Paul Kuentz ² Julien Thevenon ^{2, 33} Martine Laville ^{34, 35} Yves Reznik ³⁶ Cédric Fagour ³⁷ Marie-Laure Nunes ³⁷ Dorothée Delesalle ³⁸ Sylvie Manouvrier ³⁹ Olivier Lascols ^{40, 41, 42} Frédéric Huet ^{2, 1} Christine Binquet ⁴³ Laurence Faivre ³³ Jean-Baptiste Rivière ^{2, 1} Corinne Vigouroux ^{42, 40, 41} Pål Rasmus Njølstad ⁵ A. Micheil Innes ⁴⁴ Christel Thauvin-Robinet ^{33, 2, *}

* Corresponding author

1 CHU Dijon

2 GAD - Génétique des Anomalies du Développement

3 Children's hospital of Eastern Ontario Research Institute

4 UiB - University of Bergen

5 Haukeland University Hospital

6 Human Genetics Institute

7 Department of Paediatrics and Adolescent Medicine [HKU]

8 SW Thames Regional Genetics Service, St Georgeâ™s University of London, London

9 St George's Hospital

10 INGEMM, Instituto de Genética Médica y Molecular, IDIPAZ-Hospital Universitario La Paz

11 ISC - Instituto de Salud Carlos III [Madrid]

12 Hospital Central de la Cruz Roja San Jose y Santa Adela

13 University Hospital Puerta de Hierro, Madrid

14 Bodø University College

15 Humangenetik

16 University of Frankfurt

17 University of Melbourne

18 Victorian Clinical Genetics Services

19 Stanford University

20 SickKids - The Hospital for sick children [Toronto]

21 UCSF - University of California [San Francisco]

22 CHU Necker - Enfants Malades [AP-HP]

23 CH Le Havre

24 Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière]

25 CHU Pitié-Salpêtrière [AP-HP]

26 GRC - Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme

27 CHU Trousseau [APHP]

28 CHU Amiens-Picardie

29 Service de Pédiatrie [Jean Verdier]

30 IGDR - Institut de Génétique et Développement de Rennes

31 CHU Pontchaillou [Rennes]

32 Inserm U781 - Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement

33 Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon)

34 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition

35 CRNH-RA - Centre de Recherche en Nutrition Humaine Rhône-Alpes

36 Hôpital Côte de Nacre [CHU Caen]

37 CHU Bordeaux [Bordeaux]

38 CH Valenciennes

39 Hôpital Jeanne de Flandres

40 UPMC - Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie

41 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition

42 UMRS893 - Centre de Recherche Saint-Antoine

43 CIC-EC - Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques

44 University of Calgary

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 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) 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 : lipoatrophy SHORT syndrome PIK3R1 gene short stature Diabetes Insulin Resistance intrauterine growth restriction

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Life Sciences [q-bio] / Genetics / Human genetics

Complete list of metadata

Cited literature [15 references] Display Hide Download

https://hal-univ-rennes1.archives-ouvertes.fr/hal-01225503
Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Monday, January 25, 2016 - 2:20:57 PM
Last modification on : Thursday, September 1, 2022 - 4:04:26 AM
Long-term archiving on: : Tuesday, April 26, 2016 - 11:03:35 AM