Shank3 Duplication in Patient with an Unbalanced Translocation (20;22)(Q13.33;Q13.33)

DOI: 10.26717/BJSTR.2018.04.001069 Capkova Pavlína. Biomed J Sci & Tech Res ISSN: 2574-1241

Case Report Open Access

Capkova Pavlina*1, Capkova Zuzana2, Trkova Marie3 and Becvarova Vera4

1Department of Medical Genetics, University Hospital Olomouc, Czech Republic

2Department of Medical Genetics, Palacky University, Czech Republic

3,4Gennet, Centre for Fetal Medicine and Reproductive Genetics, Prague, Czech Republic

Received: April 10, 2018; Published: May 14, 2018

*Corresponding author: Capkova Pavlína, Department of Medical Genetics, University Hospital Olomouc, I.P.Pavlova 6, Olomouc, Czech Republic

Abstract We report subtelomeric deletion of 20q13.33 andduplication 22q13.33 resulting from unbalanced de novo translocation t(20;22) (q13.33;q13.33) in 6-year-old girl with mild mental disability, speech delay, behavioural problems, growth delay, microcephaly,minor

anddysmorphic is associated features,detected with autistic by spectrum MLPA and disorders, SNParray. severe Deletion speech spanning impairment,ADHD 1,6 Mb included, andschizophrenia.Whereas apart from ARFGAP1 and theMYT1, terminal genesKCNQ2 deletion and of 22qCHRNA4, is known which as arePhelan linked McDermid toautosomal syndrome, dominant the duplicationepilepsy.Duplicated of the same area region included is not genes so frequently RABL2B, ARSAreported. and SubtelomericSHANK3 spansapp. 20q deletions 190 kb are rare, and deletions resulting from translocation were reported only in a few cases. We review the clinical and behavioural phenotype of subtelomeric20q deletion and 22q duplication.

Introduction Subtelomeric rearrangements contribute to idiopathic mental of life. The propositus underwent physiotherapeutic interventions the first signs of developmental delay (motoric delay) at 3 months according Vojta and then Bobath concepts. At one year, she was mental retardation syndromes. However, for most subtelomeric insufficiency and human malformation, sometimes as distinct diagnosed with truncal hypotonia and developmental delay. At defects characteristic clinical phenotype remains to be elucidated. two years on clinical examination, there was persisting hypotonia, With the use of modern techniques, such as molecular karyotyping

extremities. At three years, speech delay and behavioural problems growth deficiency, developmental delay and hyperreflexia of lower (aCGH) or multiple ligation-dependent probe amplification (MLPA), (affective behaviour andnegativistic behaviour, moodiness, chromosome abnormalities can be identified in individuals with frustration/rage if the things go in other than her way, she requires nonspecific symptoms, such as developmental delay, in whom no attention) were noted. She was showing a speech delay, but the individuals with similar genotypes or genetic constitution can be particular disorder is suspected. In “genotype-first” approach, hearing loss was ruled out. MRI scan (four years and 7 months) detected, and typical phenotype, or collection of clinical features can showed a structurally normal brain with slightly expanded space of be determined.We describe a patient with subtelomeric 20q deletion temporal lobe of the right ventricle. and 22q duplication. Our report can contribute to characterization of the clinical picture of subtelomericmicrodeletion20q and 22q microduplication. simple sentences. She used to smear the stool on her body and the At five years, she used to say up to 20 words, after that she used Clinical Report The propositus was the second child of nonconsanguinous, bed linen. At five years and eight months, she was referred to our and failure to thrive. She was still suffering from enuresis. Growth healthy parents; the mother was 28 years old and father 33 years. Medical Genetics unit because of speech delay, mental insufficiency parameters were as follows: weight 18 kg (-0.93 SD), height 110 Pregnancy was uneventful; delivery was at 38th week gestation; cm (-1.2 SD), OFC 47 cm (-2.64 SD). She was not willing to tolerate Apgar score was 10-10-10, birth weight 2805 g, length 46 cm and physical examination (from any physician). Clinical examination head circumference 33 cm (10thpercentile). Paediatrician noted

shown presence of flat occiput, slightly posteriorly rotated ears, Cite this article: Capkova P, Capkova Z, Trkova M, Becvarova V. Shank3 Duplication in Patient with an Unbalanced Translocation (20;22) (Q13.33;Q13.33). Biomed J Sci &Tech Res 4(3)- 2018. BJSTR. MS.ID.001069. DOI: 10.26717/ BJSTR.2018.04.001069.

3992 Capkova Pavlína. Biomed J Sci & Tech Res Volume 4- Issue 3: 2018

otapostasis, almond shaped eyes, slight inner epicanthal fold at the left and prominent pinna (Figure 1). She actually looks like coverage of that region does notensure duplication detection. We, are guaranteed by Human CytoSNP-12v2.1 Illumina), and SNP her younger sister. She had clinodactyly of the 4th digits of lower limb but no major dysmorphic features. At this time (8 years and therefore, performed confirmation with another SALSA MLPA kits 4 months) she still has the intermittent problem with enuresis but (SALSA MLPA P245 - Microdeletions and P343 - Autism1), which she is getting better. Her mental status matches moderate mental showed duplication of SHANK3 gene. We also verified the detected disability. rsa20q13.33(P036,P070)x1;22q13.33(P036,P070,P245,P343) imbalance by FISH. The results are as follows: MLPA - 46,XX. x3;FISH- 46,XX.ish der(20)t(20;22)(qter-;qter+). Microdeletion

20q13.33 spans 1.6 Mband involves genes ARFGAP1, CHRNA4 and KCNQ2,MYT1, OPRL1. The size of 22q13.33 microduplication is approximately 190 kb and involves genes RABL2B, ARSA and sister and stepbrother were normal. SHANK3 (Figure 2) The karyotype (G band and FISH) of the parents,

Figure 1: Photographs of the patient at age 5yers eight months. Some signs of autistic spectrum disorder are present. She repeatedly uses some sounds to satisfy herself. She repeats new favourite sentences evenin the inappropriate situations. Behaviour is frequently negativistic and aggressive, she has a tendency to react Figure 2: Relevant genes involved in translocation of that the mother is not in the room. She is obstinate and impatient; chromosomes 20 and 22 (https://decipher.sanger.ac.uk). like “ see no evil, hear no evil”, she turn back on mother and pretend, e.g. she is obsessively asking about planned appointments. She may Discussion have an elevated level of pain sensitivity -she uses to stare at TV in a rigid position (knees bended to the chest), and she is squeezing her thighs without pain reaction. Methods Metaphase chromosomes preparations from a peripheral blood lymphocyte culture were obtained according to standard procedures. Chromosomes analysis was carried out on GTG banded chromosomes at a resolution of 550 bands. For MLPA (Multiplex peripheral blood by standard salting out methods. The telomere kits ligation-dependent probe amplification), DNA was extracted from were used for screening of subtelomeric rearrangements in the (SALSA MLPA P036 and P070- Telomere 3 and 5)(MRC - Holland) Figure 3 We report a case of de novo 1.6 Mb subtelomeric deletion of sample and SALSA MLPA P245 Microdeletions and P343 Autism- chromosome 20q13.33 and duplication of chromosome 22q13.33 kitfor confirmation of duplication22q13.33. Procedureswere as a result of unbalanced chromosomal translocation in the performed according manufacturer´s protocol. SNP array with probes JAG1(Alagille)/qter (Cytocell) and probe DiGeorge patient with speech delay and mental disability, but without (HumanCytoSNP-12v2.1, Illumina, Inc., San Diego, CA)and FISH major dysmorphic features and epileptic seizures. Up to 20 cases of the microdeletion 20q13.33 were reported so far [1-4] (Figure VCFS TUPLE 1/22q13.33 (Cytocell) were used for confirmation of 3). Subtelomeric deletions of the long arm of chromosome 20 are theResults MLPA results. rare. Clinical features of individuals with these microdeletions include severe limb malformations, skeletal abnormalities, growth subtelomeric microdeletion of 20q13.33 in patient, thus the The karyotype of the patient was 46,XX. SNP array revealed karyotype was 46, XX.arr 20q13.33(61,323,418-62,909,908) and seizures. There does not appear to be a clinically recognisable insufficiency, developmental and speech delay, mental insufficiency constellation of dysmorphic features among individuals with x1. SALSA MLPA Telomere 3 and 5 however detected not only subtelomeric 20q microdeletions [5]. In our patient developmental microdeletion 20q13.33 (OPRL1, UCKL1) but alsoduplication and transient growth delays were observed. array as its size is relatively small (0,2 Mb resolution of duplications 22q13.33 (RABL2B, ARSA). Duplication 22q was not detected by SNP

Biomedical Journal of Scientific & Technical Research (BJSTR) 3993 Capkova Pavlína. Biomed J Sci & Tech Res Volume 4- Issue 3: 2018

However, severe limb malformations were not present. language development in the case of dup 22qter (see Figure 2). Several studies report seizures or epilepsy in the individuals with Marked irritability and unstable temper present in our patient were

the postsynaptic density (PSD) of excitatory synapses, where it microdeletion 20q especially deletion KCNQ2 and CHRNA4 [5,6]. also reported previously [16]. SHANK3 gene encodes a protein of mutations in one allele have been noted in some patients with may function as a master scaffolding forming large sheets that may KCNQ2 encodes a subunit of voltage-gate potassium channel and benign familial neonatal seizures [7,8]. Recently mutations in represent the platform for the construction of the PSD complex

neuroligins [25] which, together with the neurexins form a complex KCNQ2 were described in patient with unexplained neonatal or [24]. At the PSD complex, SHANK3 has been shown to bind to subunit of the neuronal nicotinic acetylcholine receptor. Mutations at glutamatergic synapses. Presumably the 22q13 duplication infantile epileptic encephalopathy [9]. CHRNA4 encodes the α4 in this gene leading to a gain of function were found in some patients suffering from AD nocturnal frontal lobe epilepsy, disorder causes overexpression SHANK3 resulting in interference with that is characterized by a variety of paroxysmal behaviours that properOkamoto synaptic et development,al. [18] suggested such as that developmental the 22q13 duplicationisdeficiency. a recognisable clinical entity with hypotonia, developmental generally arise out of non-REM sleep [10]. CHRNA4 knockout mice show heightened anxiety-like behaviour [11]. No seizures or sleep in our patient. Moreover microcephaly, which was also noted in our patient suggests deletion of these genes may show incomplete delay and growth deficiency. All these symptoms were observed disturbances were observed in our patient so far. Lack of seizures in our patient, has also been reported to accompany frequently the penetrance [5]. However, we cannot exclude the later onset the duplication 22q13 [15-18]. As the microcephaly was mentioned seizures as our patient is still young. only in the Beri-Deixheimer ´s (Table 1) report of 20q13.33 microdeletion, we can assume that this abnormality is more common for duplication 22q13.33. Craniofacial abnormalities are Thehaploinsufficiency MYT1 - myelin transcription factor that opiate-like G-protein–coupled receptor that is thought to be less characteristic for 22q13.33 duplication except for prominent is highly expressed in the developing brain – and OPRL1 (encoding involved in the regulation of instinctive and emotional behaviours) arementioned to have the possible role in behavioural problems and forehead, hypertelorismand flat nasal bridge which are frequently neuro developmental delay [12]. Behavioural problems associated of these in our patient. Poor language development and mental reported in this case (Table 2). But we can not confirm the presence with the chromosomal aberration [5,13] were noted at the age of

insufficiency/developmental delay are reported in both aberrations they were not related to theautistic spectrum disorders (ASD). these abnormalities to the particular aberration. three years in our patient, but at the time of first clinical evaluation – 22q13 duplication and 20q13 deletion -so it is difficult to ascribe Whereas deletion 22q13.33 is wellknown as Phelan McDermid Conclusion syndrome, the duplication the same region has been less frequently observed [14-16] usuallyas a result of unbalanced translocation Autistic behaviour was reported in patients with sub telomeric [17,18]. The duplication detected in our patient encompasses genes micro deletion 20q13 [5,26,27] Some of the neuro behavioural problems in our patient may result from the 22q13 duplication (moodiness) but she does not suffer fromAsperger syndrome SHANK3,The 22q13duplications ACR, ARSAand RABL2B. have been reported in patients diag- or ADHD. Hyperactivity or ADHD is common in this case [14,16]. Contemporary failure, to thrive, has been described in 20q13 disorder (ADHD) or schizophrenia [16,19,20]. Hyperkinetic neu- subtelomeric deletions (Table 1). The extension of the subtelomeric nosed with Asperger syndrome, attention deficit-hyperactivity ropsychiatric disorder is caused by heterozygous interstitial du- deletion 20q13 in all reviewed reports is rather similar, butwe concluded that except for the presence of seizures andmild brain anomalies is impossible to distinguish any subtypes. plication in chromosome 22q13 involving the SHANK3 gene [14]. gene expressed predominantly in cerebral cortex and cerebellum. SHANK3 was first identified in rats [15] and then in humans as a References showed poor social interactions and repetitive behaviours [21]. As 1. Patients with duplication of SHANK3 are essentially nonverbal and monosomy 20q: a new syndrome. Regional assignment of the adenosine deaminaseFraisse J, Bertheas (ADA) locus MF, Frere on 20q13. F, Lauras Ann B, Genet Rolland 24(4): MO, 216-219.et al. (1981) Partial discussed elsewhere [19,22,23], fine tuning of the gene expression 2. Ardalan A, Prieur M, Choiset A, Turleau C, Goutieres F, et al. (2005) of speech and language and/or social communication in humans. of critical genes such as SHANK3 can be crucial for the development Intrachromosomal insertion mimicking a pericentric inversion: Molecular cytogenetic characterizations of a three break rearrangement Whereas a child, who inherited the 22q13 deletion, developed of chromosome 20.Am J Med Genet 138A(3): 288-293. an ASD phenotype, her sister who inherited a 22q13 partial trisomy 3. presented with ADHD. Similarly, in a family with a paternal balanced presentation of 13 patients with subtelomeric rearrangements and a translocation described by [19], the daughter with a 22q13 deletion reviewRoberts of AE,the literature. Cox GF, Kimonis Am J Med V, Genet Lamb 128A: A, Irons 352-363. M (2003) Clinical developed autism, severe language delay, whereas her brother 4. with a 22q13 partial trisomy, albeit the diagnosis of Asperger (2004) Screening for subtelomeric rearrangements in 210 patients with syndrome, demonstrated precocious language development and Koolen DA, Nillesen WM, Versteeg, MHA, Merkx GFM, Knoers NV, et al

5. unexplained mental retardation using MLPA. J Med Genet 41: 892-899. not cause language disability but can lead to impairment in social fluent speech. The additional copy of 22q/SHANK3 seems to do Traylor RN, Bruno DL, Burgess T, Wildin R, Spencer A, et al (2010) A communication [19]. However, some authors reported the poor genotype-first approach for the molecular and clinical characterization of uncommon de novo microdeletion of 20q13.33. PLoS One 27: 12462e.

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6. subtelomere deletion masquerading as pyridoxine-dependent epilepsy. Genet 49(5): 384-395. AmMefford J Med HC, Genet Cook 158A: J, Gospe 3190-3195. SM Jr (2012) Epilepsy due to 20q13.33 (21;22): three case reports and a review of the literature. Eur J Med 18. 7. (2007) 22q13 Microduplication in two patients with common clinical seizures with tonic clonic sequences and poor developmental outcome. manifestations:Okamoto N, Kubota A recognizable T, Nakamura syndrome? Y, Murakami Am J Med R, NishikuboGenet 143A: T, 2804- et al. Schmitt B, Wohlrab G, Sander T, Steinlein OK, Hajnal BL (2005) Neonatal 2089.

8. Epilepsy Res 65: 161-168. 19. Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, et al. (2007) Bellini G, Miceli F, Soldovieri MV, Miraglia delGiudice E, Pascotto A, et Washington,al (2010) KCNQ2 Seattle, - Related USA. disorders. In:Pagon RA, Adam MP, Ardinger Mutations in the gene encoding the synaptic scaffolding protein SHANK3 HH (Eds.) GeneReviews→ [Internet]. Seattle (WA): University of 20. areMoessner associated R, Marshall with autism CR, spectrumSutcliffe JS, disorders. Skaug J, Nat Pinto Genet D, 39:et al. 25-27. (2007) 9. Weckhuysen S, Mandelstam S, Suls A, Audenaert D, Deconic T, et al. Hum Genet 81: 1289-1297. Contribution of SHANK3 mutations to autism spectrum disorder. Am J (2012) KCNQ2 encephalopathy: Emerging phenotype of neonatal 21. 10. epileptic encephalopathy. Ann Neurol 71: 15-25. (1999) Proline-rich synapse-associated protein-1/cortactin binding proteinBoeckers 1 (ProSAP1/CortBP1) TM, Kreutz MR, Winter is a PDZ C, Zuschratterdomain protein W, SmallaKH, highly enriched et al. atHirose GeneTests: S, Kurahashi Medical H (2010) Genetics Autosomal Information dominant Resource nocturnal (database frontal online). lobe Seattle,epilepsy. WA: In: PagonUniversity RA, Birdof Washington, TD, dolan CR, USA. Stephens K (Eds.) GenReviews 22. in the postsynaptic density. J Neurosci 19(15): 6506-6518. 11. forkhead-domain gene is mutated in a severe speech and language deletion of epilepsy gene orthologs in a mutant mouse with a low Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP (2001) A electroconvulsiveYang Y, Beyer BJ, Otto threshold. JF, O’Brien Hum TP, Mol Letts Genet VA, 12(9): et al. (2003) 975-984. Spontaneous 23. disorder. Nature 413: 519-523. 12. Severe expressive-language delay related to duplication of the Williams- Somerville MJ, Mervis CB, Young EJ, Seo EJ, del Campo M, et al. (2005) 1444-1453.Romm E, Nielsen JA, Kim JG, Hudson LD (2005) Myt1 family recruits histone deacetylase to regulate neural transcription. J Neurochem 93: 24. Beuren locus. N Engl J Med 353: 1694-1701. 13. architectural framework that may lie at the core of the postsynaptic de novo 1.1-1.6 Mb subtelomeric deletion of chromosome 20q13.33 density.Baron MK, Science Boeckers 311(5760): TM, Vaida 531-535. B, Faham S, Gingery M, et al. (2006) An Bena F, Bottani A, Marcelli F, Sizonenko LD, ConradB, et al. (2007) A features. Am J Med Genet Part A 143A(16): 1894-1899. 25. in a patient with learning difficulties but without obvious dysmorphic complexity of PDZ domain-mediated interactions at glutamatergic 14. Meyer G, Varoqueaux F, Neeb A, Oschlies M, Brose N (2004) The expression causes manic-like behaviour with unique pharmacogenetic Han K, Holder JL, Schaaf CP, Lu H, Chen H, et al. (2013) SHANK3 over 26. synapses: a case study on neuroligin. Neuropharm 47: 724-733. retardation in a girl with a subtelomeric deletion on chromosome 20q 15. properties. Nature 503: 72-77. Kroepfl T, Petek E, Schwarzbraun T, Kroisel PM, Plecko B (2008) Mental aberrations in Chinese patients with unexplained developmental delay/ Clin Gen 73: 492-495. mentalWu Y, Ji retardation. T, Wang J, Xiao BMC J, MedWang Genet H (2010) 11: 72. Submicroscopic subtelomeric and complete deletion of the myelin transcription factor 1 gene (MYT1). 27. 16. Failla P, Romano C, Alberti A, Vasta A, Buono S, et al. (2007) Schizophrenia al. (2007) Genotype-phenotype correlations to aid in the prognosis in a patient with subtelomeric duplication of chromosome 22q. Clin Gen ofBe´ri-Deixheimer individuals with M, uncommon Gregoire MJ, 20q13.33 Toutain A,subtelomere Brochet K, Briaultdeletions: S, eta 71: 599-601. collaborative study on behalf of the association des Cytogene´ticiens de 17. . Cryptic duplication of the distal segment of 22q due to a translocation Feenstra I, Koolen DA, Van der Pas J, Hamel BC, Mieloo H, et al. (2006) languaeFrancaise’. Eur J Hum Genet 15(4): 446-452

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Table 1: Clinical characterisation of del (20)(q13.33) in the literature. ECARUCA Capkova Kroepfl Traylor Koolen author 2011 Béna 5 4 3 2 1 0.0925 1.1-1.6 of del [Mb] 0.56 1.08 1.61 0.52 size 1.1 1.6 1 ARFGAP1, ARFGAP1, ARFGAP1, ARFGAP1, ARFGAP1, ARFGAP1, ARFGAP1, CHRNA4, CHRNA4, CHRNA4, CHRNA4, CHRNA4, CHRNA4, CHRNA4, CHRNA4, PCMTD2 genes of interest KCNQ2, KCNQ2, KCNQ2, KCNQ2, KCNQ2, KCNQ2, KCNQ2, KCNQ2 SOX18, SOX18, SOX18, SOX18, SOX18, SOX18, SOX18 MYT1, MYT1 MYT1 MYT1 MYT1 MYT1 MYT1 aCGH, FISH aCGH, FISH MLPA,FISH SNP array, karyotype SNP array SNP array SNP array detection (q13.33) (q13.33) (q13.33) (q13.33) (q13.33) (q13.33) (q13.33) (q13.33) t(20;22) del(20) del(20) del(20) del(20) del(20) del(20) del(20) del(20) der(20) method aCGH FISH FISH 61.22- exten- (Mb) 61.2- 61.2- 60.7- 61.2- 61.7- 62.8- 61.3- 61.3- 62.2 61.8 62.3 62.3 62.3 62.3 62.9 62.4 62.9 sion (gender) 2y7m(F) 4y2m(F) 5y7m(F) 23y(M) 9y (M) 3y5m- 9y(M) 3y3m 4y(F) (M) (M) age seizures /epile- only 1 psy + + + + - - - - speech delay ++ ++ + + + + ? ? ? PMD MI ++ ++ + + + + + + - temporal forehead bifrontal minence promi- narro- wing nent pro- ? ------thickened posterio- antihelix low-set, otapos- promi- roted helix, tasis, nent ears - - - slunt on the epicanthus, convergent mongoloid mongoloid mongoloid mongoloid strabism telorism shaped, almond hyper- ptosis slunt, slunt, slight slunt slunt eyes left dysmorphic thin upper lip, long philtrum mouth - - - - nent pinna nasolabial decreased small alae - tipped, bulbous bulbous narrow promi- folds, nose nasī. - square trian- gular face/ head - - - lobe, normal perivascular dilatation in of temporal left parietal delaydmye- prominent bilaterally and cystic expanded abnormal linisation EEG, MRI temporal space, of ventricle the right anomaly slightly normal lobe of spaces brain lobes EEG EEG ? ? - - - cephaly micro- + ? ------repetitive, xious, shy, dyspraxia the lower ments of affective anxious, negativ- ballistic autistic minim. behav- action, overa- move- motor action social social inter- inter- calm poor istic, mild iour legs ? ? ? (lower hypo- laxity tonia legs) joint mild + + + ? ? - - GD + + ? ? ? - - - - (incl. clinod- clinodactyly hypospadia, riding toes tubes,over- dislocation nystagmus congenital of 4th toe of the hip club foot, club foot, actyly) others ear ? - - - -

Biomedical Journal of Scientific & Technical Research (BJSTR) 3996 Capkova Pavlína. Biomed J Sci & Tech Res Volume 4- Issue 3: 2018

Beri-Deix-

ECARUCA

heimer

delay, MI

Mefford

Ardalan

Roberts

motoric

psycho-

growth

Fraisse

insuffi-

mental

Leeuw

ciency

delay,

2006

PMD

approx

1.33

1.0

1.5

0.8

1.6

ARFGAP1,

CHRNA4,

KCNQ2,

SOX18,

MYT1

conventional

and dup(20)

karyotyping

aCGH, FISH

(p13)

(q13.33)

t(17;20)

del(20)

der(20)

del(20)

(q13)

aCGH

FISH

61.2-

60.7-

61.6-

62.9

62.4

3m (M)

5y4m-

7y(M)

7y (F)

9y(M)

4y (F)

7y(F)

(M)

irregular

seizures,

episode,

ataxia

tonic,

sleep

mild

narro-wing

temporal

narrow

promi-

large

nent

small thin

dysplastic

low-set,

malfo-

rmed

helix

mongolo-id

epicant-hic

mongoloid

epicanthic

deep-set, deep-set,

telorism,

hyperte-

elorism

hypert-

hyper-

lorism

slunt-

slunt, slunt,

slunt

folds

thin upper lip,

down-turned

smooth short

micrognathia

corners, thin

short upper

long upper

philtrum,

upper lip

philtrum

lower lip

lip, thick

short

lip

long pro-

notched

bulbous

nostrils

minent

bridge,

antev-

broad

nares

erted

trigono-

cephaly

brachy-

thin

delaydmye+-

enlargement

of temporal

thin corpus

asymmetry

ventricular

abnormal

callosum,

linisation

cerebral

atrophy,

lobes,

mild

with

EEG

and

and social

langu-age

injur-ious

sive, self-

failure to

autistic,

normal

aggres-

thrieve

action

inter-

poor

beh.

axial

clinodactyly

syndactyly,

nystagmus

of kidneys,

congenital

placement

malities,

abnorm.

cryptor-

chidism

phono-

abnor-

logical

blind,

anal

Biomedical Journal of Scientific & Technical Research (BJSTR) 3997 Capkova Pavlína. Biomed J Sci & Tech Res Volume 4- Issue 3: 2018

Table 2:

Okamoto 1

Feenstra 1

Bon/2007

ECARUCA

Capkova

author

Han 1

Failla

Clinical characterization of microduplication 22q(q13.33) in the literature.

size of

0.115-

0.258

.064-

[Mb]

0.19

>2.0

0.24

dup

6.0

4.3

5.4

0.3

SHANK3,

RABL2B,

SHANK3

RABL2B

RABL2B genes of

RABL2B

interest

ARSA,

(q13.31;q13.33))

dup(22)(q13.33)

SNP array, MLPA

(q13.33;q13.33)

der(20)t(20;22)

der(17)t(17;22)

der(21)t(21;22)

der(10)t(10;22

(p13;q13.2)pat

(p10;q13.3)pat

ma microarray,

(q13→qter)dn

(p13;q13)pat

dn SNParray,

MLPA, FISH

aCGH, FISH

FISH,MLPA

aCGH,FISH

Karyotype

detection

dup(22)

method

aCGH

FISH

3y11m

4m (F)

7m (F)

5y7m

3y7m

3y6m

6y(F)

(gen-

der)

35 y

Age

20y

11y

(M)

(F)

Seizures/

epilepsy

Speech

incoh-

erent-

delay

PMD/

prom-

inent

head

fore-

otapostasis,

prominent

deformed

low-set,-

low-set,

ioroted

low-set

poster-

hyper-

plasia

helix

ears

hypertelorism,

down-slanting

hypertelorism

shaped, slight

slunt on the

epicanthus,

strabismus

Epicanthus

mongoloid

palpebral

deep-set

epicants

fissures,

myopia,

fissures

almond

fissures

small

eyes

left

rethrognathia,

micrognathia,

down-turned

microstomia

high-arched

submucose

palate cleft

prominent

upper lip,

philtrum,

thick lips

shallow

corners

mouth

palate

prominent

anteverted

deviation

depresed

flat nasal

Pinched

of nasal

bridge

broad,

bridge

broad,

pinna

nares

septa

nose

trigono-

midface

cephaly

square

round

Face

flat

cephaly

micro-

anxious, mild

bipolar, mood

hyperactivity,

hyperactivity

schizofrenia,

hyperactive,

negativistic,

restlesness,

destructive

behaviour

aggresive

difficulty

affective,

difficulty

affective

pleasant

reaction

friendly

feeding

ADHD,

swing

tonia

hypo

stature/

growth

delay

short

myopia,some

skin and hair

ysplastic hip,

lation, hype-

clinodactyly

hypopigme-

with valgus,

of 4th toes,

overstimu-

syndactyly

pulmonar

splay foot

abnorma

scoliosis,

stenosis,

auditory

flat feet

rphagia

ntation

ectopic

kidney

others

valve

lities

CHD

skin

EEG

Biomedical Journal of Scientific & Technical Research (BJSTR) 3998 Capkova Pavlína. Biomed J Sci & Tech Res Volume 4- Issue 3: 2018

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Biomedical Journal of Scientific & Technical Research (BJSTR) 3999