SPIN4-related X-linked overgrowth in a family

Authors

• Lisanna Põlluaas, University of Tartu, Institute of Clinical Medicine, Estonia; Genetics and Personalized Medicine Clinic, Tartu University Hospital, Estonia. Electronic address: [email protected].
• Stella Lilles, University of Tartu, Institute of Clinical Medicine, Estonia; Children's Clinic, Department of General Paediatrics and Neurology, Tartu University Hospital, Estonia.
• Aleksandr Peet, University of Tartu, Institute of Clinical Medicine, Estonia; Children's Clinic, Department of General Paediatrics and Neurology, Tartu University Hospital, Estonia.
• Youn Hee Jee, Division of Endocrinology and Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA; Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Ülle Murumets, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Estonia.
• Mihkel Ilisson, University of Tartu, Institute of Clinical Medicine, Estonia; Genetics and Personalized Medicine Clinic, Tartu University Hospital, Estonia.
• Mare Lintrop, University of Tartu, Institute of Clinical Medicine, Estonia; Radiology Clinic, Tartu University Hospital, Estonia.
• Katrin Õunap, University of Tartu, Institute of Clinical Medicine, Estonia; Genetics and Personalized Medicine Clinic, Tartu University Hospital, Estonia.

Document Type

Journal Article

Publication Date

3-2-2026

Journal

European journal of medical genetics

Volume

81

DOI

10.1016/j.ejmg.2026.105073

Keywords

Epigenetic modifications; Overgrowth syndrome; SPIN4; Tall stature

Abstract

Spindlin Family Member 4 (SPIN4) is an epigenetic reader gene on the X chromosome. Its loss-of-function variant altering the WNT/β-catenin pathway was recently reported to cause a SPIN4-associated overgrowth syndrome in an extended family. The index case is a 14-year-old male with tall stature (+2.0 SD) as the only growth-related finding, accompanied by protruding joints, splenomegaly, low bone mineral density, and normal intelligence. Exome sequencing identified the same loss-of-function variant of SPIN4 (NM_001012968.3:c.312_313del:p.(Arg104Serfs*24)), which was identified in the original family. The variant was present in the proband's mother and maternal grandmother. They both had skewed X-deviation (80% and 20%) and no height gain to their mid-parental heights. The first patient with the same SPIN4 variant described by Lui et al. had more pronounced birth weight and height compared to our patient, and an advanced bone age by one year. Both patients exhibited tall stature, normal pubertal timing, psychomotor development, and intellect, as well as similar facial features and organomegaly (Lui et al., 2023).

APA Citation

Põlluaas, Lisanna; Lilles, Stella; Peet, Aleksandr; Jee, Youn Hee; Murumets, Ülle; Ilisson, Mihkel; Lintrop, Mare; and Õunap, Katrin, "SPIN4-related X-linked overgrowth in a family" (2026). GW Authored Works. Paper 8946.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8946

Department

Pediatrics