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CASE REPORT
Year : 2021  |  Volume : 69  |  Issue : 1  |  Page : 181-183

An Unexpected Cause of Ptosis: 22q11.2 Duplication Syndrome


1 Department of Pediatric Neurology, Izmir Tepecik Education and Research Hospital, Afyon, Turkey
2 Department of Pediatric Neurology, Izmir KatipCelebi University, Afyon, Turkey
3 Department of Pediatric Neurology, AfyonKocatepe University, Afyon, Turkey
4 Department of Genetics, Izmir Tepecik Education and Research Hospital, Izmir, Turkey

Date of Submission01-Nov-2018
Date of Decision01-Nov-2018
Date of Acceptance20-Jul-2019
Date of Web Publication24-Feb-2021

Correspondence Address:
Pinar Gencpinar
Department of Pediatric Neurology, Izmir Katip Celebi University, Izmir, Turkey, Cigli 35620, Izmir
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.310061

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 » Abstract 


The chromosome 22q11.2 region is highly susceptible to both microdeletions and microduplications that have been known to be responsible for multiple congenital anomaly disorders. We describe a patient of 22q11.2 duplication syndrome presenting with bilateral ptosis who has normal psychomotor development. Cranial magnetic resonance imaging and electromyography with repetitive nerve stimulation were normal. Chromosome microarray analysis was performed, and the patient was found to have a de novo 2.8 Mb duplication at 22q11.21. To our knowledge, bilateral ptosis and normal psychomotor development with 22q11.2 duplication syndrome has not been described. The 22q11.2 duplication syndrome should be considered in the differential diagnosis of ptosis. This case report contributes to an expanding clinical spectrum of patients with 22q11.2 duplication syndrome.


Keywords: Duplication syndrome, microarray analysis, ptosis
Key Message: This is the first article of bilateral ptosis associated with 22q11.2 duplication syndrome with no additional features.


How to cite this article:
Arican P, Gencpinar P, Cavusoglu D, Koc A, Dundar NO. An Unexpected Cause of Ptosis: 22q11.2 Duplication Syndrome. Neurol India 2021;69:181-3

How to cite this URL:
Arican P, Gencpinar P, Cavusoglu D, Koc A, Dundar NO. An Unexpected Cause of Ptosis: 22q11.2 Duplication Syndrome. Neurol India [serial online] 2021 [cited 2021 Apr 11];69:181-3. Available from: https://www.neurologyindia.com/text.asp?2021/69/1/181/310061




The 22q11.2 duplication syndrome is characterized by mild dysmorphic features, learning disabilities, velopharyngeal insufficiency with or without cleft palate, and heart defects.[1]Autism spectrum disorders, epilepsy, hyper nasal speech, urogenital abnormalities, and ocular abnormalities are frequently reported in patients with 22q11.2 duplication syndrome.[2],[3]

Even within families carrying the same duplication, expression of these features is variable. Although some patients are mildly affected with intellectual disability and minor dysmorphic features, others presented with severe congenital anomalies.[4] Early and precise diagnosis of the condition is imperative to provide adequate genetic counseling.

We report here a case of 22q11.2 duplication syndrome presented with ptosis. To our knowledge, this is the first clinical report of ptosis associated with 22q11.2 duplication syndrome in a patient with no additional features.


 » Case Report Top


A 16-month-old female patient was admitted to hospital with bilateral ptosis. She was the first child of consanguineous parents. Family medical history of the patient was unremarkable. She was born full-term after a normal pregnancy by vaginal delivery.

On physical examination, her weight, length, and head circumference were appropriate for her age. Neurologic examination was normal, except for bilateral severe ptosis [Figure 1]. She had good head control at one month. She could sit without support at 6 months. She could walk at 15 months. She has normal cognitive development. There were no organomegaly and dysmorphic features. Ophthalmologic examination was normal.
Figure 1: Bilateral severe ptosis in the patient

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Hemoglobin level, serum electrolytes, and creatinine kinase were normal. Cranial magnetic resonance imaging was normal. Echocardiogram revealed no abnormality. Congenital myasthenic syndromes were suspected, and electromyography was performed. Electromyography with repetitive nerve stimulation of the hypothenar muscle was normal.

For copy number variations, chromosome microarray analysis was performed using the Affymetrix GeneChip Cytoscan Optima (ThermoFisherScientic, USA). The patient was found to have a de novo 2.8 Mb duplication at 22q11.21. The microarray analysis was reported as arr[hg19] 22q11.21 (18,917,030–21,804,886) X3. The pathogenic, gain copy number variations includes “22q11 duplication syndrome region” and contains 41 OMIM genes: PRODH, DGCR2, DGCR14, TSSK2, GCS2, SLC25A1, CLTCL1, HIRA, MRPL40, UFD1L, CDC45, CLDN5, SEPT5, GP1BB, TBX1, GNB1L, TXNRD2, COMT, ARVCF, DGCR8, TMT2A, RANBP1, ZDHHC8, RTN4R, DGCR6L, RIMBP3, ZNF74, SCARF2, MED15, PI4KA, SERPIND1, SNAP29, CRKL, LZTR1, THAP7, P2RX6, SLC7A4, BCRP2, RIMBP3C, RIMBP3B, and HIC2. Parental chromosome microarray analyses were normal.

During the 20 months follow-up period, at the age of three years, the patient showed normal psychomotor development. Her psychomotor development was evaluated using the Denver developmental screening test-II (Turkish version). Four areas (fine motor adaptive, gross motor, personal-social, and language) of functioning were assessed. The result of Denver developmental screening test-II shows that the patient is within the normal and appropriate developmental growth for her age.


 » Discussion Top


Ptosis occurs in isolation or concurrently as an ocular or neurologic disease [Table 1]. Most cases of congenital ptosis unilateral and about 20–70% of patients will develop amblyopia.[5] From history and examination, a differential diagnosis of ptosis was considered in our patient. Cranial magnetic resonance imaging and electromyography were normal. Chromosome microarray analysis was performed, and we describe a patient of 22q11.2 duplication syndrome presenting with bilateral ptosis who has normal psychomotor development.
Table 1: Causes of pediatric ptosis

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Chromosome 22q11 is one of the most unstable parts of the human genome by the presence of chromosome-specific low-copy repeats or segmental duplications.[6] The 22q11.2 duplication is also associated with a wide variety of phenotypes. Several possibilities may account for phenotypic variability including variation in genetic background, additive pathogenic mutations, epigenetic factors, gene expression level, and regulatory variation among genes in rearranged regions.[7],[8]

The reported clinical findings in the 22q11.2 duplication syndrome are behavioral problems, intellectual disabilities, hearing loss, growth and developmental delay, hypotonia, microcephaly, pachygyria, seizures, urogenital anomalies, T cell deficiency, and congenital heart defects. The dysmorphic features detected are hypertelorism, broad flat nose, micrognathia, velopharyngeal insufficiency, dysplastic ears, epicanthal folds, down-slanting palpebral fissures, long narrow face, and brachydactyly.[6],[9]

The ocular abnormalities in 22q11.2 duplication syndrome are common. Refractive errors, strabismus, amblyopia, retinal vascular tortuosity, glaucoma, abnormal eye movements, and ptosis are reported in children with 22q11.2 duplication syndrome.[10] In Forbes et al. study, they found that over half of children with 22q11.2 duplication syndrome have ocular abnormalities.[3] Our patient's ophthalmologic examination was normal except bilateral ptosis. To our knowledge, bilateral ptosis and normal psychomotor development with 22q11.2 duplication syndrome have not been described.

The 22q11.2 duplication syndrome should be considered in the differential diagnosis of ptosis. It is important that early recognition of this syndrome for modifying the course of the illness and optimizing patient outcome. The variety of clinical manifestations of this syndrome indicates that a multidisciplinary approach is necessary for diagnosis, treatment, and follow-up of these patients. The 22q11.2 duplication syndrome may be difficult to recognize and diagnose in some patients because of broad phenotypic variability. This case report contributes to an expanding clinical spectrum of patients with 22q11.2 duplication syndrome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Portnoï MF. Microduplication 22q11. 2: A new chromosomal syndrome. Eur J Med Genet 2009;52:88-93.  Back to cited text no. 1
    
2.
Clements CC, Wenger TL, Zoltowski AR, Bertollo JR, Miller JS, de Marchena AB, et al. Critical region within 22q11.2 linked to higher rate of autism spectrum disorder. Mol Autism 2017;8:58.  Back to cited text no. 2
    
3.
Forbes BJ, McDonald-McGinn DM, Wootton G, Dawson L, Zackai E, Binenbaum G. Ocular findings associated with chromosome 22q11.2 duplication. J AAPOS 2016;20:278-80.  Back to cited text no. 3
    
4.
Yu S, Cox K, Friend K, Smith S, Buchheim R, Bain S, et al. Familial 22q11.2 duplication: A three-generation family with a 3-Mb duplication and a familial 1.5-Mb duplication. Clin Genet 2008;73:160-4.  Back to cited text no. 4
    
5.
Sudhakar P, Vu Q, Kosoko-Lasaki O, Palmer M. Upper eyelid ptosis revisited. Am J Clin Med 2009;6:5-14.  Back to cited text no. 5
    
6.
Capra V, Mascelli S, Garrè ML, Nozza P, Vaccari C, Bricco L, et al. Parental imbalances involving chromosomes 15q and 22q may predispose to the formation of De novo pathogenic microdeletions and microduplications in the offspring. PloSOne 2013;8:e57910.  Back to cited text no. 6
    
7.
Girirajan S, Rosenfeld JA, Coe BP, Parikh S, Friedman N, Goldstein A, et al. Phenotypic heterogeneity of genomic disorders and rare copy-number variants. N Engl J Med2012;367:1321-31.  Back to cited text no. 7
    
8.
Ou Z, Berg JS, Yonath H, Enciso VB, Miller DT, Picker J, et al. Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes. Genet Med 2008;10:267-77.  Back to cited text no. 8
    
9.
Wentzel C, Fernström M, Öhrner Y, Annerén G, Thuresson AC. Clinical variability of the 22q11.2 duplication syndrome. Eur J Med Genet 2008;51:501-10.  Back to cited text no. 9
    
10.
Cordovez JA, Capasso J, Lingao MD, Sadagopan KA, Spaeth GL, Wasserman BN, et al. Ocular manifestations of 22q11.2 microduplication. Ophthalmology 2014;121:392-8.  Back to cited text no. 10
    


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