1q44 deletion is a rare syndrome associated with facial dysmorphism and developmental delay, in particular related with expressive speech, seizures, and hypotonia (ORPHA:238769). Until today, the distinct genetic causes for the different symptoms remain not entirely clear. We present a patient with a 2.3-Mb 1q44 deletion, including AKT3, ZBTB18, and HNRNPU, who shows microcephaly, developmental delay, abnormal corpus callosum, and seizures. The genetic findings in this case and a review of the literature spotlight a region between 243 Mb and 245 Mb on chromosome 1q related to the genesis of the typical symptoms of 1q44 deletion.

1.
Ballif BC, Rosenfeld JA, Traylor R, Theisen A, Bader PI, et al: High-resolution array CGH defines critical regions and candidate genes for microcephaly, abnormalities of the corpus callosum, and seizure phenotypes in patients with microdeletions of 1q43q44. Hum Genet 131:145-156 (2012).
2.
Boland E, Clayton-Smith J, Woo VG, McKee S, Manson FD, et al: Mapping of deletion and translocation breakpoints in 1q44 implicates the serine/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum. Am J Hum Genet 81:292-303 (2007).
3.
Caliebe A, Kroes HG, van der Smagt JJ, Martin-Subero JI, Tönnies H, et al: Four patients with speech delay, seizures and variable corpus callosum thickness sharing a 0.440 Mb deletion in region 1q44 containing the HNRPU gene. Eur J Med Genet 53:179-185 (2010).
4.
Easton RM, Cho H, Roovers K, Shineman DW, Mizrahi M, et al: Role for AKT3/protein kinase Bgamma in attainment of normal brain size. Mol Cell Biol 25:1869-1878 (2005).
5.
Gai D, Haan E, Scholar M, Nicholl J, Yu S: Phenotypes of AKT3 deletion: a case report and literature review. Am J Med Genet 167:174-179 (2015).
6.
Gupta R, Agarwal M, Boqqula VR, Phadke RV, Phadke SR: Hemiconvulsion-hemiplegia-epilepsy syndrome with 1q44 microdeletion: causal or chance association. Am J Med Genet 164:186-189 (2013).
7.
Hill AD, Chang BS, Hill RS, Garraway LA, Bodell A, et al: A 2-Mb critical region implicated in the microcephaly associated with terminal 1q deletion syndrome. Am J Med Genet 143A: 1692-1698 (2007).
8.
Nagamani S, Erez A, Bay C, Pettigrew A, Lalani SR, et al: Delineation of a deletion region critical for corpus callosal abnormalities in chromosome 1q43-q44. Eur J Hum Genet 20:176-179 (2012).
9.
Orellana C, Relello M, Monfort S, Oltra S, Quiroga R, et al: Corpus callosum abnormalities and the controversy about the candidate genes located in 1q44. Cytogenet Genome Res 127:5-8 (2009).
10.
Perlman S, Kulkarni S, Manwaring L, Shinawi M: Haploinsufficiency of ZNF238 is associated with corpus callosum abnormalities in 1q44 deletions. Am J Med Genet 161A:711-716 (2013).
11.
Raun N, Mailo J, Spinelli E, He X, McAvena S, et al: Quantitative phenotypic and network analysis of 1q44 microdeletion for microcephaly. Am J Med Genet A 173:972-977 (2017).
12.
Selmer K, Bryne E, Rodningne OK, Fannemel M: A de novo 163 kb interstitial 1q44 microdeletion in a boy with thin corpus callosum, psychomotor delay and seizures. Eur J Med Genet 55:715-718 (2012).
13.
Thierry G, Beneteau C, Pichon O, Flori E, Isidor B, et al: Molecular characterization of 1q44 microdeletion in 11 patients reveals three candidate genes for intellectual disability and seizures. Am J Med Genet 158A:1633-1640 (2012).
14.
Westphal DS, Andres S, Beitzel KI, Makowski C, Meitinger T, Hoefle J: Identification of a de novo microdeletion 1q44 in a patient with hypogenesis of the corpus callosum, seizures and microcephaly - a case report. Gene 616:41-44 (2017).
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