Wiedemann-Steiner syndrome diagnosis in a patient with clinical suspicion of Rubinstein-Taybi syndrome

Silveira, H. G., Battison, G. S., Nunes, B. C., Luce, A. L. P., Melo, D. G., Melaragno, M. I. (2025). Wiedemann-Steiner syndrome diagnosis in a patient with clinical suspicion of Rubinstein-Taybi syndrome(Version 1) [DataSet]. GestaltMatcher Database.

We report a 14-year-old Brazilian female patient, the only child of non-consanguineous parents, who had global developmental delay, facial dysmorphisms, and recurrent respiratory and urinary infections. She exhibited behavioral immaturity and learning difficulties, without stereotypies or aggressive behavior. Growth hormone replacement began at nine years of age due to short stature. Physical examination revealed multiple dysmorphic features, including craniofacial anomalies (bitemporal narrowing, arched and thick eyebrows, synophrys, long eyelashes, downslanting palpebral fissures, ptosis, hypertelorism, low-set ears, bulbous nasal tip, low hanging columella, apparent short philtrum, and high-arched palate, and microdontia) and digital anomalies (mild clinodactyly, broad thumbs and halluces, hallux valgus, and digital pads). Additional findings included diffuse hypertrichosis, delayed bone age, strabismus, and recurrent infections. Based on clinical scoring, Rubinstein-Taybi syndrome (RSTS, OMIM #180849) was initially suspected. However, whole exome sequencing identified a heterozygous pathogenic variant in the KMT2A gene (OMIM *159555), confirming a diagnosis of Wiedemann-Steiner syndrome (WSTS, OMIM #605130). These two conditions have extensive phenotypic overlap, and the presence of shared features in this patient further challenged the clinical diagnosis. This case shows it is generally more readily recognized to suspect a well-described and widely reported syndrome than a less characterized and rarer one. Notably, GestaltMatcher analysis of facial photographs reinforced the diagnosis, ranking WSTS as the most likely (distance: 0.566) and RSTS as the second most suggestive condition (distance: 0.602).