A Novel Variant in a Patient with Primrose Syndrome: A Rare Clinical Entity with Distinctive Features.

Introduction: Primrose syndrome (PS; MIM #259050) is a rare autosomal dominant genetic condition characterized by macrocephaly with or without tall stature, hypotonia, moderate to severe intellectual disability (ID) with delay in expressive speech development, behavioral abnormalities, and a recognizable facial phenotype including deep set eyes, ptosis, narrow and frequently downslanting palpebral fissures, and depressed nasal bridge. PS is caused by a heterozygous pathogenic variant in (MIM #606025) on chromosome 3q13. Among other characteristic findings are ocular abnormalities, hearing loss, calcification of the external ear cartilage, nonspecific brain magnetic resonance imaging findings, and cryptorchidism. Adults may exhibit joint contractures, distal muscle wasting, sparse body hair, cataract, and disturbed glucose metabolism as well. The majority of affected individuals have typically been adults until recently since the phenotype becomes more recognizable in time.

Case Presentation: In this study, we report on a 14-month-old girl who presented with neurodevelopmental findings, facial features, and hearing loss. The glucose metabolism was normal, and muscle atrophy, joint contractures, and external ear cartilage calcification were yet hitherto not evident. A novel de novo missense variant in was identified with the aid of exome sequencing.

Conclusion: PS is a rare clinical entity with various recognizable features, yet the phenotype may be indistinguishable from other neurodevelopmental disorders. Exome sequencing is a useful diagnostic tool especially in patients with no specific diagnosis despite detailed examinations and imaging studies.