IMPE2023 Poster Presentations Diabetes and Insulin (16 abstracts)
POC1A gene defect in two unrelated cases with severe dyslipidemic insulin resistance and SOFT syndrome
María Esnaola Azcoiti 1 , Ana Keselman 1 , Nora Sanguineti 1 , Carolina Crespo 2 , Gabriela Krochik 3 , Mariana Costanzo 4 , Paula Scaglia 1 , Agustín Izquierdo 1 , Miriam Tonietti 5 , Hilda Verónica Aráoz 2 , Luis Pablo Gravina 2 , Débora Braslavsky 1 , Bárbara Casali 1 , Florencia Villegas 6 , Lourdes Correa 1 , María Gabriela Obregón 7 , Claudia Arberas 6 , Rodolfo Rey 1 , Ignacio Bergadá 1 , Cristina Noemí Alonso 8 & Gabriela Ropelato 1
1Centro de Investigaciones Endocrinológicas "Dr. César Bergadá" (CEDIE) CONICET – FEI – División de Endocrinología, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 2Laboratorio Biología Molecular Genética, Hospital de Pediatría Prof. Dr. Juan P Garrahan, Buenos Aires, Argentina. 3Servicio de Nutrición, Hospital de Pediatría Prof. Dr. Juan P Garrahan, Buenos Aires, Argentina. 4Servicio de Endocrinología Infantil, Hospital de Pediatría Prof. Dr. Juan P Garrahan, Buenos Aires, Argentina. 5Servicio de Nutrición, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 6Servicio de Genética, Hospital de Niños Ricardo Gutiérrez, Buenos Aires, Argentina. 7Servicio de Genética, Hospital de Pediatría Prof. Dr. Juan P Garrahan, Buenos Aires, Argentina. 8Área Laboratorios Especializados, Hospital de Pediatría Prof. Dr. Juan P Garrahan, Buenos Aires, Argentina
Introduction: SOFT syndrome (MIM#614813), denoting Short stature, Onychodysplasia, Facial dysmorphism, and hypoTrichosis, is a rare primordial dwarfism syndrome encompassing severe growth failure of prenatal onset, craniofacial dysmorphism, sparse hair, and digital abnormalities associated with biallelic pathogenic POC1Agene variants. Phenotypic spectrum has recently been expanded to include insulin resistance (IR) and muscle cramps.
Aim: To describe two unrelated cases from Argentina presenting SOFT syndrome with severe IR associated to a homozygous POC1A variant.
Case 1: A 10-month-old girl referred for short stature evaluation, born from non-consanguineous parents, at term (38 weeks GA), SGA (BW:-3.93 SD). At first visit, she presented weight -3.7 SD, height -6.2 SD, head circumference (HC) -1.6 SD, BMI 15.3 (10-25centile). At 9.3 years old, height was -3.8 SD and she had gained substantially weight (BMI 19.8;88centile) presenting central obesity, acanthosis nigricans, severe IR, glucose intolerance, hypertriglyceridemia, and hepatic steatosis. She was treated with metformin but progressed to diabetes mellitus. Physical examination showed microcephaly (HC -2.4SD), triangular facies, wide forehead, prominent nasal bridge, micrognathia, high-pitched voice, broad fingers, and normal neurodevelopment. She also developed severe muscle cramps, with elevated serum CPK. She presented normal GH and elevated IGF1 and IGFBP3 levels.
Case 2: A 5-year-old boy born to parents of normal height at 31 weeks of GA, BW:1870g (-0.98SD), referred due to adrenal hyperandrogenism with advanced bone age. At the age of 8, weight was 30.6 kg (1 SD), height: 123 cm (-0.53 SD), BMI: 20.2 (1.69SD). Further clinical features included dry hair, triangular face, wide forehead, hypertelorism, ptosis, depressed nasal bridge, microretrognathia, acanthosis nigricans, central obesity and normal neurodevelopment. He presented subaortic membrane and left ventricular hypertrophy, requiring surgery. Metabolic assessment showed severe IR, hypertriglyceridemia, and hepatic steatosis. He was treated with metformin at the age of 11 but progressed to glucose intolerance. His predicted adult height is 148.7 cm (-3.5SD). Whole exome sequencing revealed a homozygous variant in POC1Ain both patients: NM_015426.5:c.649C>T(NP_056241.3:p.Arg217Trp), classified as likely pathogenic (PM2_supp, PP3_supp, PM3_strong, PS4_supp). Studied parents (3/4) were heterozygous carriers for the variant. This variant has previously been reported in 3 patients as homozygous or compound heterozygous (PMID:30569574,35234134).
Conclusion: Patients with POC1A:NP_056241.3:p.Arg217Trp variant can develop SOFT syndrome with severe dyslipidemic IR and muscle cramps, a rare clinical presentation for this condition. These cases highlight the importance of reporting patients with POC1A pathogenic variants to further delineate and expand the clinical spectrum associated to this gene defect.
Article tools
My recent searches
My recently viewed abstracts
Authors
IMPE Abstracts
© Bioscientifica 2025 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more