The prevalence of neurological involvement in patients with a deletion of or a variant in the HNF1B gene remains discussed. The aim of this study was to investigate the neuropsychological outcomes in a large cohort of children carrying either a HNF1B whole-gene deletion or a disease-associated variant, revealed by the presence of kidney anomalies. The neuropsychological development—based on school level—of 223 children included in this prospective cohort was studied. Data from 180 children were available for analysis. Patients mean age was 9.6 years, with 39.9% of girls. Among these patients, 119 carried a HNF1B deletion and 61 a disease-associated variant. In the school-aged population, 12.7 and 3.6% of patients carrying a HNF1B deletion and a disease-associated variant had special educational needs, respectively. Therefore, the presence of a HNF1B deletion increases the risk to present with a neuropsychiatric involvement when compared with the general population. On the other hand, almost 90% of patients carrying a HNF1B disease-associated variant or deletion have a normal schooling in a general educational environment. Even if these findings do not predict the risk of neuropsychiatric disease at adulthood, most patients diagnosed secondary to kidney anomalies do not show a neurological outcome severe enough to impede standard schooling at elementary school. These results should be taken into account in prenatal counseling.
Subscribe to Journal
Get full journal access for 1 year
only $99.08 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Barbacci E. Variant hepatocyte nuclear factor 1 is required for visceral endoderm specification. Development. 1999;126AD:4795–805. 11.
El-Khairi R, Vallier L. The role of hepatocyte nuclear factor 1β in disease and development. Diabetes Obes Metab. 2016;18:23–32.
Heidet L, Decramer S, Pawtowski A, Moriniere V, Bandin F, Knebelmann B, et al. Spectrum of HNF1B mutations in a large cohort of patients who harbor renal diseases. Clin J Am Soc Nephrol. 2010;5:1079–90.
Laffargue F, Bourthoumieu S, Llanas B, Baudouin V, Lahoche A, Morin D, et al. Towards a new point of view on the phenotype of patients with a 17q12 microdeletion syndrome. Arch Dis Child. 2015;100:259–64.
Moreno-De-Luca D, Mulle JG, Kaminsky EB, Sanders SJ, Myers SM, Adam MP, et al. Deletion 17q12 is a recurrent copy number variant that confers high risk of autism and schizophrenia. Am J Hum Genet. 2010;87:618–30.
Rasmussen M, Vestergaard EM, Graakjaer J, Petkov Y, Bache I, Fagerberg C, et al. 17q12 deletion and duplication syndrome in Denmark—a clinical cohort of 38 patients and review of the literature. Am J Med Genet Part A. 2016 http://doi.wiley.com/10.1002/ajmg.a.37848. Accessed 23 Aug 2016.
Chen C-P, Chang S-D, Wang T-H, Wang L-K, Tsai J-D, Liu Y-P, et al. Detection of recurrent transmission of 17q12 microdeletion by array comparative genomic hybridization in a fetus with prenatally diagnosed hydronephrosis, hydroureter, and multicystic kidney, and variable clinical spectrum in the family. Taiwan J Obstet Gynecol. 2013;52:551–7.
Clissold RL, Shaw-Smith C, Turnpenny P, Bunce B, Bockenhauer D, Kerecuk L, et al. Chromosome 17q12 microdeletions but not intragenic HNF1B mutations link developmental kidney disease and psychiatric disorder. Kidney Int. 2016 http://www.sciencedirect.com/science/article/pii/S0085253816301156. Accessed 23 Aug 2016.
Dubois-Laforgue D, Bellanné-Chantelot C, Charles P, Jacquette A, Larger E, Ciangura C, et al. Intellectual disability in patients with MODY due to hepatocyte nuclear factor 1B (HNF1B) molecular defects. Diabetes Metab. 2017;43:89–92.
Girirajan S, Rosenfeld JA, Coe BP, Parikh S, Friedman N, Goldstein A, et al. Phenotypic heterogeneity of genomic disorders and rare copy-number variants. New Engl J Med. 2012;367:1321–31.
Decramer S, Parant O, Beaufils S, Clauin S, Guillou C, Kessler S, et al. Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. J Am Soc Nephrol. 2007;18:923–33.
Bellanne-Chantelot C, Clauin S, Chauveau D, Collin P, Daumont M, Douillard C, et al. Large genomic rearrangements in the hepatocyte nuclear factor-1 (TCF2) gene are the most frequent cause of maturity-onset diabetes of the young type 5. Diabetes. 2005;54:3126–32.
Sequence Variant Nomenclature. https://varnomen.hgvs.org/bg-material/basics/. Accessed 19 Jun 2019.
Rosenwald F. Repères et références statistiques sur les enseignements, la formation et la recherche 2018. education.gouv.fr: 2018. http://www.education.gouv.fr/cid57096/reperes-et-references-statistiques.html. Accessed 23 Dec 2018.
Loirat C, Bellanne-Chantelot C, Husson I, Deschenes G, Guigonis V, Chabane N. Autism in three patients with cystic or hyperechogenic kidneys and chromosome 17q12 deletion. Nephrol Dial Transpl. 2010;25:3430–3.
Abellán A, Vernier B, Rétaux S, Medina L. Similarities and differences in the forebrain expression of Lhx1 and Lhx5 between chicken and mouse: Insights for understanding telencephalic development and evolution. J Comp Neurol. 2010;518:3512–28.
Girirajan S, Dennis MY, Baker C, Malig M, Coe BP, Campbell CD, et al. Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder. Am J Hum Genet. 2013;92:221–37.
Bae C-J, Jeong J, Saint-Jeannet J-P. A novel function for Egr4 in posterior hindbrain development. Sci Rep. 2015;5:7750.
Wiellette EL. vhnf1 and Fgf signals synergize to specify rhombomere identity in the zebrafish hindbrain. Development. 2003;130:3821–9.
Makki N, Capecchi MR. Identification of novel Hoxa1 downstream targets regulating hindbrain, neural crest and inner ear development. Dev Biol. 2011;357:295–304.
Clissold RL, Ashfield B, Burrage J, Hannon E, Bingham C, Mill J, et al. Genome-wide methylomic analysis in individuals with HNF1B intragenic mutation and 17q12 microdeletion. Clin Epigenetics . 2018;10. https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-018-0530-z. Accessed 26 Dec 2018.
Gilboa Y, Perlman S, Pode-Shakked N, Pode-Shakked B, Shrim A, Azaria-Lahav E, et al. Prenatal diagnosis of 17q12 deletion syndrome: from fetal hyperechogenic kidneys to high risk for autism: prenatal echogenic kidneys and autism in 17q12 deletions. Prenat Diagn 2016;36:1027–32.
Conflict of interest
The authors declare that they have no conflict of interest.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Laliève, F., Decramer, S., Heidet, L. et al. School level of children carrying a HNF1B variant or a deletion. Eur J Hum Genet (2019) doi:10.1038/s41431-019-0490-6