nach oben

Journal of Medical Case Reports

Erschienen in:

Open Access 01.12.2022 | Case report

Wisconsin syndrome with brain volume laterality: a case report and review of the literature

verfasst von: Satomi Okano, Yoshio Makita, Kayano Kimura, Ikue Fukuda, Akie Miyamoto, Hajime Tanaka

Erschienen in: Journal of Medical Case Reports | Ausgabe 1/2022

Abstract

Background

Wisconsin syndrome is a congenital anomaly caused by a 3q interstitial deletion. It is associated with characteristic facies and developmental delays. Only 33 cases with a deletion estimated to be in the associated region 3q25 have been reported.

Case report

We present the case of a 5-year-old Japanese girl with a 3q24q25.2 deletion. Her facial features corresponded to the Wisconsin syndrome phenotype, and she exhibited brain volume laterality, which has not been reported previously.

Conclusion

The clinical features of our case may contribute to narrowing down the list of candidate genes of Wisconsin syndrome.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Introduction

Wisconsin syndrome (WS) is a congenital anomaly caused by a rare 3q interstitial deletion. The region associated with WS is estimated to be 3q25. However, the causative gene remains unknown [1]. WS was proposed by Cohen and MacLean [2] on the basis of the clinical manifestations reported by Opitz in 1976. Ferraris et al. suggested that WS should be diagnosed when finding at least four of the five following core morphologic features: coarse face, prominent or wide triangular-shaped nasal tip, high arched or upsweeping eyebrows, full/everted lower lips, and bushy eyebrows, often with synophrys [3]. It is known that Dandy–Walker syndrome (DWS) is often a complication of WS. Here, we present the WS case of a Japanese girl with reduced volume of the right occipital lobe and thalamus, which had not been reported previously. Furthermore, we summarize the clinical features reported in the literature and discuss genes potentially responsible for WS.

Case report

The patient was the first girl born to healthy nonconsanguineous parents. She was born via normal transvaginal delivery at 40 weeks and 1 day of gestation, weighing 3340 g [± 0.85 standard deviation (SD)] with a length of 51.5 cm (± 1.47 SD) and an occipitofrontal circumference of 35 cm (± 1.50 SD). She could control her neck at 5 months, sit alone at 7 months, and walk independently at 16 months. Despite the absence of hearing loss, she could not speak meaningful words until 2 years of age. She was admitted to our hospital at 5 years of age. She had arched eyebrows, flat nasal tip, broad ala nasi, prominent ears, full everted lips, and a mouth that was always open. Cardiac auscultation results were normal. We did not find any abnormalities or laterality in the extremities. The deep tendon reflex was normal, and there was no paresthesia. She had mild intellectual disability (intelligence quotient 69 by the Tanaka–Binet intelligence test) and dysarthria, but she could read Japanese characters and count to 10. A vision test was not performed, and she went to kindergarten without trouble. There were no abnormal findings in the blood test. Brain magnetic resonance imaging revealed volume reduction in the right occipital lobe and thalamus (Fig. 1a, b). Circumference of right/left occipital lobe was 85.5 mm/88.4 mm, and that of right/left thalamus was 43.3 mm/68.6 mm. Laterality did not exist in the language center. Electroencephalography showed no laterality or paroxysm. She is currently receiving speech therapy at our hospital.

Ethical approval for this study was obtained from the Asahikawa Habilitation Center for Children Ethics Committee (ref. no. R01-19). After written informed consent was obtained from her parents in proxy of the patient, we performed a genetic examination. The results of the chromosomal analysis were 46, XX, del [3] (q25.q25.3). The microarray analysis confirmed arr[hg19] 3q24q25.2 (147,510.640-154,810,046) × 1, a 7.3 Mb heterozygous interstitial deletion in the long arm of chromosome 3.

Discussion and conclusions

We diagnosed our patient with WS because the facial appearance fulfilled the clinical criteria proposed by Ferraris et al. [3]. These clinical manifestations are seen frequently in WS cases; hence, they have high diagnostic value (Table 1).

Table 1

The proportion of previously reported clinical manifestations

Clinical manifestation	Positive/mentioned	Proportion (%)
High arched eyebrow^a	13/13	100
Developmental delay	32/32	100
Coarse face^a	21/22	95.4
Wide nasal tip^a	19/20	95.0
Full/everted lower lip^a	16/17	94.1
Bushy eyebrow^a	12/14	85.7
Dandy–Walker syndrome	17/21	81.0
Smooth philtrum	8/10	80.0
Ear anomalies	14/18	77.8
Macrostomia	6/9	66.7
Recessed fourth foot	5/13	38.5
Cardiac defect	5/14	35.7

Ratio of the symptomatic case to cases that mentioned the presence of a symptom. ^aEssential clinical manifestations for diagnosis suggested by Ferraris et al. [3].

A literature search using PubMed confirmed 33 cases of 3q interstitial deletions in WS patients, including 3q25, which is considered the associated region of WS (Table 2) [1‐22]. One mosaic case was excluded from the analysis. The main clinical features of WS, including a specific facial appearance, developmental delay of various levels, and some lower limb anomalies such as recessed fourth toe or clubfoot, were found in these cases.

Table 2.

Clinical manifestations of our case and previous reports

References	Deletion	DWS	Coarse face	Wide nasal tip	High arched eyebrow	Full everted lips	Bushy eyebrow	Smooth philtrum	Macrostomia	Developmental delay	Ear anomaly	Recessed fourth foot	Cardiac defect	Other features
Okano	3q24q25.2	−	+	+	+	+	+	−	+	+	+	−	−
Franceschini [4]	3q23q26	NM	+	+	+	+	+	NM	NM	+	NM	NM	−	Deafness
Martsolf⁵	3q23q25	NM	+	+	NM	−	+	NM	NM	+	+	NM	+
Cohen [2]	3q23q25	NM	+	+	+	+	+	+	−	+	+	+	NM
Al-Awadi [6]	3q23q25	NM	+	+	+	+	+	NM	NM	+	+	+	+	Clubfoot
Alvard [7]	3q23q25	NM	+	+	+	+	−	−	+	+	+	−	+
Robin [8]	3q25.1q26.1	NM	+	+	NM	+	NM	NM	NM	+	+	NM	NM
Chandler [9]	3q23q25	NM	+	+	NM	NM	NM	NM	NM	+	+	NM	NM
Slavotinek [10]	3q25	NM	+	+	NM	+	NM	NM	NM	+	+	NM	NM
Costa [11]	3q22.2q25.1	NM	+	+	NM	+	NM	+	NM	+	−	NM	NM	Hypospadias
Sudha [12]	3q25.1q25.3	+	+	+	+	NM	+	+	−	+	+	−	+
Ko [13]	3q24q26.1	NM	+	+	+	+	+	NM	NM	+	+	+	−
Grinberg [14]^a		+	NM	NM	NM	NM	NM	NM	NM	+	NM	NM	NM
Rea [15]	3q22.3q25.1	NM	−	−	NM	NM	NM	NM	NM	+	+	−	+
Lim [16]	3q22.3q25.1	+	+	NM	NM	NM	NM	NM	NM	+	Nm	NM	NM
Tohyama [17]	3q23q25.1	+	+	+	NM	+	NM	NM	NM	+	NM	NM	NM
Weber [18]	3q23q25.1	+	+	NM	NM	NM	NM	NM	NM	+	NM	NM	NM	CAKUT
Willemsen [1]	3q24q25.33	−	+	+	+	+	+	+	+	+	−	−	−
Willemsen [1]	3q25.1q25.3	NM	+	+	+	+	+	+	−	+	−	−	−
Moortgat [19]	3q25.1q25.3	−	+	+	+	+	+	+	+	+	+	−	−	Alopecia
D’Amours [20]	3q25.1q25.3	+	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM	NM
Ferraris [3]	3q22.3q25.3	+	+	+	+	+	+	+	+	+	+	+	−
Ferraris [3]	3q22q26.1	−	+	+	+	+	−	+	+	+	−	+	−	Epilepsy,MPSIII
Chang [21]	3q25.33	−	+	+	+	+	+	NM	NM	+	+	−	−
Bertini [22]	3q24q25.2	+	+	+	+	+	+	−	+	+	+	−	−

Listed in chronological order.

+ present, − absent

NM not mentioned in the article, DWS Dandy–Walker syndrome, CAKUT congenital anomalies of kidney and urinary tract, MPS mucopolysaccharidosis

^aGrinberg et al. [14] reported ten cases of DWS and developmental delay carrying a 3q interstitial deletion. Their deletions were: 3q22.2q25.3, 3q22q26, 3q23q25.3, 3q23q23.31, 3q23q25.1, 3q24q25.1, 3q22.2q25, 3q25.1q25.3, 3q22.3q25.2, and 3q22.1q25.1. Other clinical features were unclear.

Regarding brain anomalies, only DWS was reported, and we could not find any other case with laterality of brain parenchyma. Neurological symptoms of our patient included mild intellectual disability and dysarthria; therefore, the clinical significance of brain laterality was unclear. Further analyses, such as functional magnetic resonance imaging, are needed to understand the relationship between clinical symptoms and imaging results.

The prognosis of WS depends on the occurrence of serious complications such as cardiac disease. Previously reported cardiac anomalies include ventricular heart septal defects, truncus arteriosus, and mitral and tricuspid prolapse. Willemsen et al. reported a 60-year-old female WS patient with typical facial features and intellectual disability, but without visceral disease, except for primary amenorrhea [1].

The zinc-finger protein of cerebellum 1 (ZIC1, MIM *600470) and zinc-finger protein of cerebellum 4 (ZIC4, MIM*608948) genes on 3q24 are known to cause DWS [23]. Although DWS is frequently observed in WS, this complication does not depend on deletion of the 3q24 region, as shown in Table 2. This difference was not caused by the resolution of G-banding because an array analysis was delineated in at least ten WS cases and the results were similar. Thus, ZIC1 and ZIC4 might not be essential for brain malformations in WS.

In the 3q24q25.2 region deleted in our case, there are five long intergenic noncoding RNAs, 12 genes for which published symbols are not available, and 10 identified genes: SMARCA3 (MIM*603257), TM4SF1 (MIM*191155), WWTR1 (MIM*607397), GYG1 (MIM*603942), CPB1 (MIM*114852), CPA3 (MIM*114851), AGTR1 (MIM*106165), MBNL1 (MIM*606516), ZIC1, and ZIC4. Bertini et al. proposed MBNL1 as a candidate gene for WS [22]. We speculate that WWTR1 on chromosome 3q25.1 might also be a candidate gene in consideration of its encoded protein function. WWTR1 is a key downstream component of the Hippo-YAP/TAZ pathway that regulates organ size and tissue homeostasis. It promotes growth and many mitogenic hormones and growth factors acting through G-protein-coupled receptors [24]. The brain volume difference in our case raises the possibility that WS occurs owing to the absence of WWTR1.

In summary, we present a case of WS with brain parenchyma laterality. To elucidate the genetic and molecular aspects of WS, an accumulation of cases is necessary.

Acknowledgements

We thank the patient and her family, Associate Professor Satoru Takahashi, Dr. Ryosuke Tanaka, Dr. Ryo Takeguchi, and Dr. Mami Kuroda of Asahikawa Medical University, Department of Pediatrics, who cooperated with magnetic resonance imaging scanning.

Declarations

Ethical approval was obtained from the Asahikawa Habilitation Center for Children Ethics Committee (ref. no. R01-19).

Written informed consent was obtained from the patient's legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interest

The authors declare that they have no competing interest.

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Unsere Produktempfehlungen

e.Med Interdisziplinär

Kombi-Abonnement

Für Ihren Erfolg in Klinik und Praxis - Die beste Hilfe in Ihrem Arbeitsalltag

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de.

Jetzt testen ¹

e.Med Allgemeinmedizin

Kombi-Abonnement

Mit e.Med Allgemeinmedizin erhalten Sie Zugang zu allen CME-Fortbildungen und Premium-Inhalten der allgemeinmedizinischen Zeitschriften, inklusive einer gedruckten Allgemeinmedizin-Zeitschrift Ihrer Wahl.

Jetzt testen ²

Willemsen MH, Leeuw N, Mercer C, et al. Further molecular and clinical delineation of the Wisconsin syndrome phenotype associated with interstitial 3q24q25. Am J Med Genet A. 2011;155A(1):106–12.CrossRefPubMed

Cohen MMJ, MacLean RA. editors. Wisconsin Syndrome. Craniosynostosis: Diagnosis, Evaluation, and Management, 2nd ed. Oxford University Press, New York, 2000; pp. 432–3.

Ferraris A, Bernardini L, Sabolic Avramovska VS, et al. Dandy–Walker malformation and Wisconsin syndrome: novel cases add further insight into the genotype–phenotype correlations of 3q23q25 deletions. Orphanet J Rare Dis. 2013;8:75.CrossRefPubMedPubMedCentral

Franceschini P, Cirillo Silengo M, Davi G, et al. Interstitial deletion of the long arm chromosome 3 in a patient with mental retardation and congenital anomalies. Hum Genet. 1983;64(1):97.CrossRefPubMed

Martsolf JT, Ray M. Interstitial deletion of the long arm of chromosome 3. Ann Genet. 1983;26(2):97–9.

Al-Awadi SA, Naguib KK, Farag TI, et al. Complex translocation involving chromosomes Y,1, and 3 resulting in deletion of segment 3q23→q25. J Med Genet. 1986;23(1):91–2.CrossRefPubMedPubMedCentral

Alvarado M, Bocian M, Walker AP. Interstitial deletion of the long arm of chromosome 3: case report, review, and definition of a phenotype. Am J Med Genet. 1987;27(4):781–6.CrossRefPubMed

Robin NH, Magnusson M, McDonald-McGinn D, et al. De novo interstitial deletion of the long arm of chromosome 3:46, XX, del (3)(q25.1q26.1). Clin Genet. 1993;44(6):335–7.CrossRefPubMed

Chandler KE, de Die-Smulders CE, Engelen JJ, et al. Severe feeding problems and congenital laryngostenosis in a patient with 3q23 deletion. Eur J Pediatr. 1997;156(8):636–8.CrossRefPubMed

10.

Slavotinek AM, Huson SM, Fitchett M. Interstitial deletion of band 3q25. J Med Genet. 1997;34(5):430–2.CrossRefPubMedPubMedCentral

11.

Costa T, Pashby R, Huggins M, et al. Deletion 3q in two patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). J Pediatr Ophthalmol Strabismus. 1998;35(5):271–6.CrossRefPubMed

12.

Sudha T, Dawson AJ, Prasad AN, et al. De novo interstitial long arm deletion of chromosome 3 with facial dysmorphism, Dandy–Walker variant malformation and hydrocephalus. Clin Dysmorphol. 2001;10(3):193–6.CrossRefPubMed

13.

Ko WT, Lam WF, Lo F, et al. Wisconsin syndrome in a patient with interstitial deletion of the long arm of chromosome 3: further delineation of the phenotype. Am J Med Genet. 2003;120(3):413–7.CrossRef

14.

Grinberg I, Northrup H, Ardinger H, et al. Heterozygous deletion of the linked genes ZIC1 and ZIC4 is involved in Dandy–Walker malformation. Nat Genet. 2004;36(10):1053–5.CrossRefPubMed

15.

Rea G, McCullough S, McNerlan S, et al. Delineation of a recognizable phenotype of interstitial deletion 3(q22.3q25.1) in a case with previously unreported truncus arteriosus. Eur J Med Genet. 2010;53(3):162–7.CrossRefPubMed

16.

Lim BC, Park WY, Seo EJ, et al. De novo interstitial deletion of 3q22.3-q25.2 encompassing FOXL2, ATR, ZIC1, and ZIC4 in a patient with blepharophimosis/ptosis/epicanthus inversus syndrome, Dandy–Walker malformation, and global developmental delay. J Child Neurol. 2011;26(5):615–8.CrossRefPubMed

17.

Tohyama J, Kato M, Kawasaki S, et al. Dandy–Walker malformation associated with heterozygous ZIC1 and ZIC4 deletion: report of a new patient. Am J Med Genet A. 2011;155A(1):130–3.CrossRefPubMed

18.

Weber S, Landwehr C, Renkert M, et al. Mapping candidate regions and genes for congenital anomalies of the kidneys and urinary tract (CAKUT) by array-based comparative genomic hybridization. Nephrol Dial Transplant. 2011;26(1):136–43.CrossRefPubMed

19.

Moortgat S, Verellen-Dumoulin C, Maystadt I, et al. Developmental delay and facial dysmorphism in a child with an 89 Mb de novo interstitial deletion of 3q25.1-q25.32: genotype–phenotype correlations of chromosome 3q25 deletion syndrome. Eur J Med Genet. 2011;54(2):177–80.CrossRefPubMed

20.

D’Amours G, Kibar Z, Mathonnet G, et al. Whole-genome array CGH identifies pathogenic copy number variations in fetuses with major malformations and a normal karyotype. Clin Genet. 2012;81(2):128–41.CrossRefPubMed

21.

Chang YT, Wang CH, Chou IC, et al. Case report of chromosome 3q25 deletion syndrome or mucopolysaccharidosis IIIB. Biomedicine. 2014;4(1):34–7.CrossRef

22.

Bertini V, Orsini A, Mazza R, et al. A 6.5 mb deletion at 3q24q25.2 narrows Wisconsin syndrome critical region to a 750kb interval: a potential role for MBNL1. Am J Med Genet A. 2017;173(1):280–4.CrossRefPubMed

23.

Blank MC, Grinberg I, Aryee E, et al. Multiple developmental programs are altered by loss of Zic1 and Zic4 to cause Dandy–Walker malformation cerebellar pathogenesis. Development. 2011;138(6):1207–16.CrossRefPubMedPubMedCentral

24.

Yu FX, Zhao B, Guan KL. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell. 2015;163(4):811–28.CrossRefPubMedPubMedCentral

Titel: Wisconsin syndrome with brain volume laterality: a case report and review of the literature
verfasst von: Satomi Okano
Yoshio Makita
Kayano Kimura
Ikue Fukuda
Akie Miyamoto
Hajime Tanaka
Publikationsdatum: 01.12.2022
Verlag: BioMed Central
Erschienen in: Journal of Medical Case Reports / Ausgabe 1/2022
Elektronische ISSN: 1752-1947
DOI: https://doi.org/10.1186/s13256-022-03332-8

Springer Medizin

Abstract

Background

Case report

Conclusion

Publisher’s Note

Introduction

Case report

Discussion and conclusions

Acknowledgements

Declarations

Ethics approval and consent to participate

Consent for publication

Competing interest

Publisher’s Note

Unsere Produktempfehlungen

e.Med Interdisziplinär

e.Med Allgemeinmedizin

Weitere Artikel der Ausgabe 1/2022

Arthrogryposis multiplex congenita in a child with congenital fractures: a case report

Successful management of a patient with ovarian ectopic pregnancy by the end of the first trimester: a case report

Pneumococcal pericarditis in a patient with newly diagnosed diabetes mellitus: a case report

Malignant complications of celiac disease: a case series and review of the literature

Early use of airway pressure release ventilation in acute respiratory distress syndrome induced by coronavirus disease 2019: a case report

Diagnosis of tuberculosis with autoimmune hepatitis–systemic lupus erythematosus overlap syndrome: a case report