A filipino child presenting with primrose syndrome with a deletion on the zbtb20 gene variant

Background: Intellectual disability in association with congenital anomalies affects 1-3% of the population, and due to its diversity, diagnosis can be challenging. Primrose syndrome is one of these rare genetic conditions that present with such disability and anomalies.  It is difficult to recognize early due to the limited number of reported case, and the more identifiable and distinct features manifest at a later age. This syndrome is caused by a defect in the ZBTB20 gene, reported as either a microdeletion or a missense variation. Both variants exhibit overlapping clinical manifestations, including intellectual disability, psychomotor delay and characteristic facial features (macrocephaly, prominent forehead, down slanting palpebral fissures, ptosis and large ears).  Other common features include skeletal malformations, normal birth weight and overgrowth. Missense variants specifically present with additional features such as muscle wasting and calcifications in the brain and pinnae, which are not observed in the microdeletion variant. Furthermore, corpus callosum abnormalities, diabetes mellitus and endocrine complications are more commonly associated with the missense variant with the microdeletion variant.

This report aims to present the case of an 8 year old Filipino female who was diagnosed with laryngomalacia, patent ductus arteriosus, and mild tricuspid regurgitation, global developmental delay and dysmorphic features (ocular anomalies, high anterior hairline, sparse eyebrows, down-slanted palpebral fissures, and a high palate).  Chromosomal analysis showed a normal female karyotype. However, next generation sequencing of a Neurodevelopmental Gene Panel revealed a heterozygous deletion of the entire ZBTB20 gene. This confirms Primrose syndrome in this child.  The features this patient indeed aligns more with the microdeletion/copy number variant (CNV)  phenotype described in literature.  Management and surveillance guidelines emphasized evaluating for neurodevelopmental issues, hearing, eye, endocrine, and rarely, skeletal problems.

Conclusion: Patients with intellectual disability and multiple anomalies may benefit from DNA testing.  Confirmation of the diagnosis in this patient guided the healthcare team in the multidisciplinary approach, including addressing the developmental concerns at this age. 

Dr. Triane Claire Lastimosa is a licensed pharmacist and currently a Pediatric resident physician at Cebu Doctors’ University Hospital in Cebu, Philippines. She earned her Doctor of Medicine degree from Cebu Doctors’ University.