Abstract
Weiss-Kruszka syndrome (WSKA; OMIM#618619) is a rare condition with multiple congenital anomalies. This study describes a patient with WSKA from Northern China. The patient was a 9.75-year-old boy who presented with growth retardation (growth velocity: 3-4 cm/year at school age), delayed motor and speech development, and eating difficulty. The patient’s weight was 22 kg (<3rd percentile), and his height was 125.6 cm (<3rd percentile) at the first visit. He had craniofacial anomalies characterized by heavily arched eyebrows, mild bilateral ptosis, inner epicanthal folds, uneven teeth, macrodontia of the upper central incisors, and low-set ears. A transverse palmar crease was observed on the right palm. The serum insulin-like growth factor-1 level was 73.1 ng/mL (normal range: 74-388 ng/mL). His bone age was appropriate at 9-10 years. Cranial magnetic resonance imaging results revealed a small pituitary gland. Trio whole-exome sequencing was performed because of the patient’s non-specific dysmorphic features and a phenotype indistinguishable from many other inherited disorders with growth retardation. A de novo splicing variant, c.6833-2A>T, was identified in the ZNF462 gene (NM_021224). Recombinant human growth hormone therapy was started (dose, 0.15 IU/kg/day) and administered as daily subcutaneous injections. His growth velocity increased (5 cm/6 months). This case has been added to the limited number of publications reporting WSKA. This study also reports the genotypic and phenotypic landscape of WKSA, providing clinical and genetic data to support the etiology of haploinsufficiency of the ZNF462 gene, as postulated by previous studies.
Keywords: ZNF462 gene, genotypic, phenotypic, Weiss-Kruszka syndrome
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References
Kruszka P. Weiss-Kruszka Syndrome. 2019 Oct 31. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews ® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. https://www.ncbi.nlm.nih.gov/books/NBK549204/
Kruszka P, Hu T, Hong S, Signer R, Cogné B, Isidor B, Mazzola SE, Giltay JC, van Gassen KLI, England EM, Pais L, Ockeloen CW, Sanchez-Lara PA, Kinning E, Adams DJ, Treat K, Torres-Martinez W, Bedeschi MF, Iascone M, Blaney S, Bell O, Tan TY, Delrue MA, Jurgens J, Barry BJ, Engle EC, Savage SK, Fleischer N, Martinez-Agosto JA, Boycott K, Zackai EH, Muenke M. Phenotype delineation of ZNF462 related syndrome. Am J Med Genet A 2019;179:2075-2082.
Weiss K, Wigby K, Fannemel M, Henderson LB, Beck N, Ghali N, Study DDD, Anderlid BM, Lundin J, Hamosh A, Jones MC, Ghedia S, Muenke M, Kruszka P. Haploinsufficiency of ZNF462 is associated with craniofacial anomalies, corpus callosum dysgenesis, ptosis, and developmental delay. Eur J Hum Genet. 2017;25:946-951. Epub 2017 May 17
Talisetti A, Forrester SR, Gregory D, Johnson L, Schneider MC, Kimonis VE. Temtamy-like syndrome associated with translocation of 2p24 and 9q32. Clin Dysmorphol. 2003;12:175-177.
Cosemans N, Vandenhove L, Maljaars J, Van Esch H, Devriendt K, Baldwin A, Fryns JP, Noens I, Peeters H. ZNF462 and KLF12 are disrupted by a de novo translocation in a patient with syndromic intellectual disability and autism spectrum disorder. Eur J Med Genet. 2018;61:376-383. Epub 2018 Feb 7
González-Tarancón R, Salvador-Rupérez E, Miramar Gallart MD, Barroso E, Díez García-Prieto I, Pérez Delgado R, López Pisón J, García Jiménez MC. A novel mutation in the ZNF462 gene c.3306dup; p.(Gln1103Thrfs*10) is associated to Weiss-Kruszka syndrome. A case report. Acta Clin Belg. 2022;77:118-121. Epub 2020 Jun 16
Park J, Ha DJ, Seo GH, Maeng S, Kang SM, Kim S, Lee JE. Empty Sella syndrome associated with growth hormone deficiency: the first case report of Weiss-Kruszka syndrome. J Korean Med Sci. 2021;36:e133.
Iivonen AP, Kärkinen J, Yellapragada V, Sidoroff V, Almusa H, Vaaralahti K, Raivio T. Kallmann syndrome in a patient with Weiss-Kruszka syndrome and a de novo deletion in 9q31.2. Eur J Endocrinol. 2021;185:57-66.
Zhao S, Miao C, Wang X, Lu Y, Liu H, Zhang X. A nonsense variant of ZNF462 gene associated with Weiss-Kruszka syndrome-like manifestations: a case study and literature review. Front Genet. 2022;13:781832.
Pellino G, Chiasso L, Fiori G, Mazzone S, Zama D, Cordelli DM, Russo A. Acute lymphoblastic leukemia in a child with Weiss-Kruszka syndrome: casual or causal association? Eur J Med Genet. 2022;65:104457.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405-424.
Chang YS, Stoykova A, Chowdhury K, Gruss P. Graded expression of Zfp462 in the embryonic mouse cerebral cortex. Gene Expr Patterns. 2007;7:405-412.
Eberl HC, Spruijt CG, Kelstrup CD, Vermeulen M, Mann M. A map of general and specialized chromatin readers in mouse tissues generated by label-free interaction proteomics. Mol Cell. 2013;49:368-378. Epub 2012 Nov 29
Laurent A, Masse J, Omilli F, Deschamps S, Richard-Parpaillon L, Chartrain I, Pellerin I. ZFPIP/Zfp462 is maternally required for proper early Xenopus laevis development. Dev Biol. 2009;327:169-176. Epub 2008 Dec 16
Massé J, Laurent A, Nicol B, Guerrier D, Pellerin I, Deschamps S. Involvement of ZFPIP/Zfp462 in chromatin integrity and survival of P19 pluripotent cells. Exp Cell Res. 2010;316:1190-1201.
Almouzni G, Probst AV. Heterochromatin maintenance and establishment: lessons from the mouse pericentromere. Nucleus 2011;2:332-338.
Beisel C, Paro R. Silencing chromatin: comparing modes and mechanisms. Nat Rev Genet. 2011;12:123-135. Epub 2011 Jan 11
Ren J, Martienssen RA. Silent decision: HP1 protein escorts heterochromatic RNAs to their destiny. EMBO J. 2012;31:3237-3238. Epub 2012 Jun 15
