TY - JOUR
T1 - Phenotypic spectrum of Au–Kline syndrome
T2 - a report of six new cases and review of the literature
AU - Care for Rare Canada Consortium
AU - Au, P. Y.Billie
AU - Goedhart, Caitlin
AU - Ferguson, Marcia
AU - Breckpot, Jeroen
AU - Devriendt, Koenraad
AU - Wierenga, Klaas
AU - Fanning, Elizabeth
AU - Grange, Dorothy K.
AU - Graham, Gail E.
AU - Galarreta, Carolina
AU - Jones, Marilyn C.
AU - Kini, Usha
AU - Stewart, Helen
AU - Parboosingh, Jillian S.
AU - Kline, Antonie D.
AU - Innes, A. Micheil
N1 - Publisher Copyright:
© 2018, European Society of Human Genetics.
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Au–Kline syndrome (AKS, OMIM 616580) is a multiple malformation syndrome, first reported in 2015, associated with intellectual disability. AKS has been associated with de novo loss-of-function variants in HNRNPK (heterogeneous ribonucleoprotein K), and to date, only four of these patients have been described in the literature. Recently, an additional patient with a missense variant in HNRNPK was also reported. These patients have striking facial dysmorphic features, including long palpebral fissures, ptosis, deeply grooved tongue, broad nose, and down-turned mouth. Patients frequently also have skeletal and connective tissue anomalies, craniosynostosis, congenital heart malformations, and renal anomalies. In this report, we describe six new patients and review the clinical information on all reported AKS patients, further delineating the phenotype of AKS. There are now a total of 9 patients with de novo loss-of-function variants in HNRNPK, one individual with a de novo missense variant in addition to 3 patients with de novo deletions of 9q21.32 that encompass HNRNPK. While there is considerable overlap between AKS and Kabuki syndrome (KS), these additional patients demonstrate that AKS does have a distinct facial gestalt and phenotype that can be differentiated from KS. This growing AKS patient cohort also informs an emerging approach to management and health surveillance for these patients.
AB - Au–Kline syndrome (AKS, OMIM 616580) is a multiple malformation syndrome, first reported in 2015, associated with intellectual disability. AKS has been associated with de novo loss-of-function variants in HNRNPK (heterogeneous ribonucleoprotein K), and to date, only four of these patients have been described in the literature. Recently, an additional patient with a missense variant in HNRNPK was also reported. These patients have striking facial dysmorphic features, including long palpebral fissures, ptosis, deeply grooved tongue, broad nose, and down-turned mouth. Patients frequently also have skeletal and connective tissue anomalies, craniosynostosis, congenital heart malformations, and renal anomalies. In this report, we describe six new patients and review the clinical information on all reported AKS patients, further delineating the phenotype of AKS. There are now a total of 9 patients with de novo loss-of-function variants in HNRNPK, one individual with a de novo missense variant in addition to 3 patients with de novo deletions of 9q21.32 that encompass HNRNPK. While there is considerable overlap between AKS and Kabuki syndrome (KS), these additional patients demonstrate that AKS does have a distinct facial gestalt and phenotype that can be differentiated from KS. This growing AKS patient cohort also informs an emerging approach to management and health surveillance for these patients.
UR - http://www.scopus.com/inward/record.url?scp=85048543179&partnerID=8YFLogxK
U2 - 10.1038/s41431-018-0187-2
DO - 10.1038/s41431-018-0187-2
M3 - Article
C2 - 29904177
AN - SCOPUS:85048543179
SN - 1018-4813
VL - 26
SP - 1272
EP - 1281
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 9
ER -