Expanding the phenotypic spectrum of ARCN1-related syndrome

Alyssa L. Ritter , Jessica Gold , Hiroshi Hayashi , Amanda M. Ackermann , Stephanie Hanke , Cara Skraban , Sanmati Cuddapah , Elizabeth Bhoj , Dong Li , Yukiko Kuroda , Jessica Wen , Ryojun Takeda , Audrey Bibb , Salima El Chehadeh , Amélie Piton (1, 2) , Jeanine Ohl , Mary K. Kukolich , Keisuke Nagasaki , Kohji Kato , Tomoo Ogi , Tricia Bhatti , Pierre Russo , Bryan Krock , Jill R. Murrell , Jennifer A. Sullivan , Vandana Shashi , Nicholas Stong , Hakon Hakonarson , Kentaro Sawano , Erin Torti , Rebecca Willaert , Yue Si , William Ross Wilcox , Katrine Verena Wirgenes , Kristian Thomassen , Katherine Carlotti , Angelika Erwin , Joanna Lazier , Thorsten Marquardt , Miao He , Andrew C. Edmondson , Kosuke Izumi

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

PURPOSE: This study aimed to describe the phenotypic and molecular characteristics of ARCN1-related syndrome. METHODS: Patients with ARCN1 variants were identified, and clinician researchers were connected using GeneMatcher and physician referrals. Clinical histories were collected from each patient. RESULTS: In total, we identified 14 cases of ARCN1-related syndrome, (9 pediatrics, and 5 fetal cases from 3 families). The clinical features these newly identified cases were compared to 6 previously reported cases for a total of 20 cases. Intrauterine growth restriction, micrognathia, and short stature were present in all patients. Other common features included prematurity (11/15, 73.3%), developmental delay (10/14, 71.4%), genitourinary malformations in males (6/8, 75%), and microcephaly (12/15, 80%). Novel features of ARCN1-related syndrome included transient liver dysfunction and specific glycosylation abnormalities during illness, giant cell hepatitis, hepatoblastoma, cataracts, and lethal skeletal manifestations. Developmental delay was seen in 73% of patients, but only 3 patients had intellectual disability, which is less common than previously reported. CONCLUSION: ARCN1-related syndrome presents with a wide clinical spectrum ranging from a severe embryonic lethal syndrome to a mild syndrome with intrauterine growth restriction, micrognathia, and short stature without intellectual disability. Patients with ARCN1-related syndrome should be monitored for liver dysfunction during illness, cataracts, and hepatoblastoma. Additional research to further define the phenotypic spectrum and possible genotype-phenotype correlations are required.

Domaines: Génétique

Alyssa L. Ritter, Jessica Gold, Hiroshi Hayashi, Amanda M. Ackermann, Stephanie Hanke, et al.. Expanding the phenotypic spectrum of ARCN1-related syndrome. Genetics in Medicine, 2022, 24 (6), pp.1227-1237. ⟨10.1016/j.gim.2022.02.005⟩. ⟨hal-04219146⟩