Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities.
Cali E., Suri M., Scala M., Ferla MP., Alavi S., Faqeih EA., Bijlsma EK., Wigby KM., Baralle D., Mehrjardi MYV., Schwab J., Platzer K., Steindl K., Hashem M., Jones M., Niyazov DM., Jacober J., Littlejohn RO., Weis D., Zadeh N., Rodan L., Goldenberg A., Lecoquierre F., Dutra-Clarke M., Horvath G., Young D., Orenstein N., Bawazeer S., Vulto-van Silfhout AT., Herenger Y., Dehghani M., Seyedhassani SM., Bahreini A., Nasab ME., Ercan-Sencicek AG., Firoozfar Z., Movahedinia M., Efthymiou S., Striano P., Karimiani EG., Salpietro V., Taylor JC., Redman M., Stegmann APA., Laner A., Abdel-Salam G., Li M., Bengala M., Müller AJ., Digilio MC., Rauch A., Gunel M., Titheradge H., Schweitzer DN., Kraus A., Valenzuela I., McLean SD., Phornphutkul C., Salih M., Begtrup A., Schnur RE., Torti E., Haack TB., Prada CE., Alkuraya FS., Houlden H., Maroofian R.
PurposeProtein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder.MethodsWe assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature.ResultsThe main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss.ConclusionThis study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities.