Renpenning syndrome in a Brazilian male with a recurrent PQBP1 c.459_462del variant

Moretti, J. (2026). Renpenning syndrome in a Brazilian male with a recurrent PQBP1 c.459_462del variant (Version 1) [DataSet]. GestaltMatcher Database.

The patient is a Brazilian male, the fifth child of non-consanguineous parents. The first pregnancy ended in third-trimester intrauterine fetal death and the second in first-trimester miscarriage. Two older sisters have normal neurodevelopment. A first-degree maternal cousin reportedly has a similar phenotype, and a maternal aunt has intellectual disability; neither relative was clinically evaluated in our service.

Prenatally, the patient presented with intrauterine growth restriction. He was born at term with a birth weight of 2,510 g (-1.58 SD), length of 45 cm (-2.39 SD), and occipitofrontal circumference of 31 cm (-2.23 SD). During childhood, he developed global developmental delay, intellectual disability, autistic behavior, microcephaly, and failure to thrive and was first evaluated by a clinical geneticist at 8 years of age.

At 20 years of age, whole-genome sequencing identified a hemizygous pathogenic variant in PQBP1, NM001032382.2:c.459462del, p.(Arg153Serfs*41). This recurrent frameshift variant is a well-established cause of PQBP1-related Renpenning syndrome.

At the most recent evaluation at 23 years of age, his weight was 42 kg (-2.0 SD), height 158 cm (-2.57 SD), and occip itofrontal circumference 52.8 cm (-3.13 SD). Physical examination showed microbrachycephaly, a long and narrow triangular face, large protruding ears, thick eyebrows, bilateral ptosis, pectus excavatum, reduced bilateral testicular volume, generalized joint laxity, and slender toes. The overall clinical and facial phenotype was consistent with Renpenning syndrome.

Conclusion: This case represents a molecularly confirmed diagnosis of Renpenning syndrome caused by the recurrent PQBP1 c.459_462del, p.(Arg153Serfs*41) variant. To our knowledge, this is among the first molecularly confirmed reports of Renpenning syndrome in the Brazilian population.