Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Case Reports
. 2021 Jul 2;47(1):148.
doi: 10.1186/s13052-021-01101-9.

Expanding the neurological and behavioral phenotype of White-Sutton syndrome: a case report

Bernadette Donnarumma  1 , Maria Pia Riccio  2 , Gaetano Terrone  1   2 , Melania Palma  1 , Pietro Strisciuglio  1 , Iris Scala  3
Affiliations
Case Reports

Expanding the neurological and behavioral phenotype of White-Sutton syndrome: a case report

Bernadette Donnarumma et al. Ital J Pediatr. .

Abstract

Background: White-Sutton (WHSUS) is a recently recognized syndrome caused by mutations of the POGZ gene. Approximately 70 patients have been reported to date. Intellectual disability, hypotonia, behavioral abnormalities, autism, and typical facial dysmorphisms are recognized as WHSUS features; however, still few patients receive a comprehensive psychometric, behavioral and neurological examination. In this report, we describe the pediatric, dysmorphological, neurological, psychometric and behavioral phenotype in a new WHSUS patient due to a novel heterozygous POGZ mutation, highlighting the distinctive epileptic phenotype and the cognitive pattern.

Case presentation: The patient, an 8 years-old girl, presented history of hypotonia, motor and speech delay, and distinctive facial features. The diagnosis of WHSUS followed the identification of the de novo variant p.Asp828GlyfsTer36 (c.2482dupG) in the POGZ gene. The patient showed a distinctive neurological phenotype with the occurrence of both paroxysmal not-epileptic events in the first 6 months of age and EEG abnormalities without evidence of clinical seizures after the first year of age. Psychological and behavioral testing highlighted moderate intellectual and communication deficit, mild autism spectrum and visual-motor integration deficit.

Conclusions: This is the first described case of WHSUS with a co-existence of paroxysmal not-epileptic events and abnormal EEG without seizures in the same patient. Together with the available literature data, this observation suggests that paroxysmal not-epileptic events could be more frequent than expected and that this feature belongs to the WHSUS phenotypic spectrum. Autism is a known comorbidity of WHSUS but is still poorly investigated. Specific clinical testing could help detect also mild autistic phenotypes and better define autism prevalence in POGZ-related syndrome. Special attention should be given to symptoms such as stereotypies, social withdrawal, and hyperactivity that, when present, should be considered as possible signs of autism symptoms. The dissection of the neurological and behavioral phenotype is crucial for individualized therapies tailored to patient's needs.

Keywords: Autism; Case report; Cognitive profile; EEG abnormalities; Epilepsy; POGZ; POGZ mutation; Paroxysmal not-epileptic events; White-Sutton syndrome.

PubMed Disclaimer

Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Electroencephalograms at 6 months (A), 14 months (B) and 8 years old (C)
See this image and copyright information in PMC

References

    1. Nozawa RS, Nagao K, Masuda HT, Iwasaki O, Hirota T, Nozaki N, Kimura H, Obuse C. Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation. Nat Cell Biol. 2010;12(7):719–727. doi: 10.1038/ncb2075. - DOI - PubMed
    1. Dentici ML, Niceta M, Pantaleoni F, Barresi S, Bencivenga P, Dallapiccola B, Digilio MC, Tartaglia M. (). Expanding the phenotypic spectrum of truncating POGZ mutations: association with CNS malformations, skeletal abnormalities, and distinctive facial dysmorphism. Am J Med Genet A. 2017;173(7):1965–1969. doi: 10.1002/ajmg.a.38255. - DOI - PubMed
    1. White J, Beck CR, Harel T, Posey JE, Jhangiani SN, Tang S, Farwell KD, Powis Z, Mendelsohn NJ, Baker JA, Pollack L, Mason KJ, Wierenga KJ, Arrington DK, Hall M, Psychogios A, Fairbrother L, Walkiewicz M, Person RE, Niu Z, Zhang J, Rosenfeld JA, Muzny DM, Eng C, Beaudet AL, Lupski JR, Boerwinkle E, Gibbs RA, Yang Y, Xia F, Sutton VR. POGZ truncating alleles cause syndromic intellectual disability. Genome Med. 2016;8(1):3. doi: 10.1186/s13073-015-0253-0. - DOI - PMC - PubMed
    1. Assia Batzir N, Posey JE, Song X, Akdemir ZC, Rosenfeld JA, Brown CW, Chen E, Holtrop SG, Mizerik E, Nieto Moreno M, Payne K, Raas-Rothschild A, Scott R, Vernon HJ, Zadeh N, Baylor-Hopkins Center for Mendelian Genomics. Lupski JR, Sutton VR. Phenotypic expansion of POGZ-related intellectual disability syndrome (White-Sutton syndrome) Am J Med Genet A. 2020;182:38–52. doi: 10.1002/ajmg.a.61380. - DOI - PMC - PubMed
    1. Garde A, Cornaton J, Sorlin A, Moutton S, Nicolas C, Juif C, Geneviève D, Perrin L, Khau-Van-Kien P, Smol T, Vincent-Delorme C, Isidor B, Cogné B, Afenjar A, Keren B, Coubes C, Prieur F, Toutain A, Trousselet Y, Bourgouin S, Gonin-Olympiade C, Giraudat K, Piton A, Gérard B, Odent S, Tessier F, Lemasson L, Heide S, Gelineau AC, Sarret C, Miret A, Schaefer E, Piard J, Mathevet R, Boucon M, Bruel AL, Mau-Them FT, Chevarin M, Vitobello A, Philippe C, Thauvin-Robinet C, Faivre L. Neuropsychological study in 19 French patients with White-Sutton syndrome and POGZ mutations. Clin Genet. 2021;99:407–417. doi: 10.1111/cge.13894. - DOI - PubMed

Publication types