Pauline Marzin1,2, Briac Thierry3,4, Andrea Dancasius1,2, Anne Cavau1, Caroline Michot1,2, Sophie Rondeau1,2, Geneviève Baujat1,2, Gilles Phan5, Maryse Bonnière6, Muriel Le Bourgeois7, Diala Khraiche8, Zagorka Pejin9, Damien Bonnet8,10, Christophe Delacourt7, Valérie Cormier-Daire11,12. 1. Fédération de Génétique médicale, Centre de référence pour les maladies osseuses constitutionnelles AP-HP, Hôpital Necker-Enfants malades, Paris, France. 2. Université de Paris, UMR1163, INSERM, Institut Imagine, Paris, France. 3. ENT pediatric department, AP-HP, Necker Children Hospital, Paris, France. 4. Université de Paris UMR976, INSERM, Paris, France. 5. Université de Paris, UMR8038, CNRS, Faculté de Pharmacie, Paris, France. 6. Service de fœtopathologie, AP-HP, Hôpital Necker-Enfants malades, Paris, France. 7. Service de Pneumologie et Allergologie Pédiatriques, AP-HP, Hôpital Necker-Enfants malades, Paris, France. 8. M3C-Necker, Cardiologie Congénitale et Pédiatrique, AP-HP, Hôpital Necker-Enfants malades, Paris, France. 9. Service de chirurgie orthopédique pédiatrique, hôpital Necker-Enfants-Malades, Paris, France. 10. Université de Paris, Sorbonne Paris Cité, Paris, France. 11. Fédération de Génétique médicale, Centre de référence pour les maladies osseuses constitutionnelles AP-HP, Hôpital Necker-Enfants malades, Paris, France. valerie.cormier-daire@inserm.fr. 12. Université de Paris, UMR1163, INSERM, Institut Imagine, Paris, France. valerie.cormier-daire@inserm.fr.
Abstract
PURPOSE: Geleophysic dysplasia (GD) and acromicric dysplasia (AD) are characterized by short stature, short extremities, and progressive joint limitation. In GD, cardiorespiratory involvement can result in poor prognosis. Dominant variants in the FBN1 and LTBP3 genes are responsible for AD or GD, whereas recessive variants in the ADAMTSL2 gene are responsible for GD only. The aim of this study was to define the natural history of these disorders and to establish genotype-phenotype correlations. METHODS: This monocentric retrospective study was conducted between January 2008 and December 2018 in a pediatric tertiary care center and included patients with AD or GD with identified variants (FBN1, LTBP3, or ADAMTSL2). RESULTS: Twenty-two patients with GD (12 ADAMTSL2, 8 FBN1, 2 LTBP3) and 16 patients with AD (15 FBN1, 1 LTBP3) were included. Early death occurred in eight GD and one AD. Among GD patients, 68% presented with heart valve disease and 25% developed upper airway obstruction. No AD patient developed life-threatening cardiorespiratory issues. A greater proportion of patients with either a FBN1 cysteine variant or ADAMTSL2 variants had a poor outcome. CONCLUSION: GD and AD are progressive multisystemic disorders with life-threatening complications associated with specific genotype. A careful multidisciplinary follow-up is needed.
PURPOSE: Geleophysic dysplasia (GD) and acromicric dysplasia (AD) are characterized by short stature, short extremities, and progressive joint limitation. In GD, cardiorespiratory involvement can result in poor prognosis. Dominant variants in the FBN1 and LTBP3 genes are responsible for AD or GD, whereas recessive variants in the ADAMTSL2 gene are responsible for GD only. The aim of this study was to define the natural history of these disorders and to establish genotype-phenotype correlations. METHODS: This monocentric retrospective study was conducted between January 2008 and December 2018 in a pediatric tertiary care center and included patients with AD or GD with identified variants (FBN1, LTBP3, or ADAMTSL2). RESULTS: Twenty-two patients with GD (12 ADAMTSL2, 8 FBN1, 2 LTBP3) and 16 patients with AD (15 FBN1, 1 LTBP3) were included. Early death occurred in eight GD and one AD. Among GD patients, 68% presented with heart valve disease and 25% developed upper airway obstruction. No AD patient developed life-threatening cardiorespiratory issues. A greater proportion of patients with either a FBN1 cysteine variant or ADAMTSL2 variants had a poor outcome. CONCLUSION: GD and AD are progressive multisystemic disorders with life-threatening complications associated with specific genotype. A careful multidisciplinary follow-up is needed.
Authors: Silke Peeters; Pauline De Kinderen; Josephina A N Meester; Aline Verstraeten; Bart L Loeys Journal: Hum Mutat Date: 2022-04-28 Impact factor: 4.700
Authors: Dena R Matalon; David A Stevenson; Elizabeth J Bhoj; Avni B Santani; Beth Keena; Meryl S Cohen; Angela E Lin; Sarah E Sheppard; Elaine H Zackai Journal: Am J Med Genet A Date: 2021-03-08 Impact factor: 2.802