SPIN4-related X-linked overgrowth in a family

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).