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Interesting case report

Association of structural and numerical anomalies of chromosome 22 in a patient with syndromic intellectual disability

Rania Naoufal, Marine Legendre, Dominique Couet, Brigitte Gilbert-Dussardier, Alain Kitzis, Frederic Bilan, Radu Harbuz


Array comparative genomic hybridization (aCGH) is now widely adopted as a first-tier clinical diagnostic test for patients with developmental delay (DD)/intellectual disability (ID), autism spectrum disorders, and multiple congenital anomalies. Nevertheless, classic karyotyping still has its impact in diagnosing genetic diseases, particularly mosaic cases. We report on a 30 year old patient with syndromic intellectual disability, a 22q13.2 microdeletion and mosaic trisomy 22. The patient had the following clinical features: intrauterine growth retardation at birth, hypotonia, cryptorchidism, facial asymmetry, enophthalmus, mild prognathism, bifid uvula, hypoplastic upper limb phalanges, DD including speech delay, and ID. Whole genome aCGH showed a de novo 1 Mb interstitial heterozygous deletion in 22q13.2, confirmed by fluorescence in situ hybridization in all cells examined. Moreover, 18% cells had an extra chromosome 22 suggesting a trisomy 22 mosaicism. Almost all 22q13 deletions published so far have been terminal deletions with variable sizes (100 kb to over 9 Mb). Very few cases of interstitial 22q13.2 deletions were reported. In its mosaic form, trisomy 22 is compatible with life, and there are about 20 reports in the literature. It has a variable clinical presentation: growth restriction, dysmorphic features, cardiovascular abnormalities, hemihyperplasia, genitourinary tract anomalies and ID. Neurodevelopmental outcome ranges from normal to severe DD. The patient presents clinical features that are common to both the interstitial 22q13 deletion and the mosaic trisomy 22; characteristics related to the interstitial deletion alone and others explained solely by the mosaic trisomy. Our case points out the role of conventional cytogenetic tools in mosaic cases that could be missed by microarray technology. We therefore suggest the combination of both conventional and molecular karyotyping in the investigation of certain genetic diseases.  

Fig.1 The patient's 22q13 deletion with reported overlapping deletions: localization and gene content; viewed in the UCSC human genome browser, GRCh37, hg 19.

Fig. 2. Photograph of the patient at adult age. Patient has a facial asymmetry due to facial palsy, prominent supraorbital ridges, enophtalmia, proganathism, high arched palate, bifid uvula, and thin upper lip.

History File

Previously published Interesting case reports

7p22.1 microduplication syndrome: Refinement of the critical region
Interpretation of clinical relevance of X-chromosome copy number variations identified in a large cohort of individuals with cognitive disorders and/or congenital anomalies
De novo microdeletions of chromosome 6q14.1-q14.3 and 6q12.1-q14.1 in two patients with intellectual disability - further delineation of the 6q14 microdeletion syndrome and review of the literature
2p21 Deletions in hypotonia-cystinuria syndrome
Duplication of 8q12 encompassing CHD7 is associated with a distinct phenotype but without duane anomaly
A de novo 4.4-Mb microdeletion in 2p24.3/p24.2 in a girl with bilateral hearing impairment, microcephaly, digit abnormalities and Feingold syndrome
A novel de novo 1.8 Mb microdeletion of 17q21.33 associated with intellectual disability and dysmorphic features
An atypical 0.8 Mb inherited duplication of 22q11.2 associated with psychomotor impairment
Molecular cytogenetic characterization of 2p23.2p23.3 deletion in a child with developmental delay, hypotonia and cryptorchism
A newborn with a 790 kb chromosome 17p13.3 microduplication presenting with aortic stenosis, microcephaly and dysmorphic facial features - Is cardiac assessment necessary for all patients with 17p13.3 microduplication?
Interstitial 16p13.3 microduplication: Case report and critical review of genotype-phenotype correlation
Prenatal diagnosis of the duplication 17p11.2 associated with PotockieLupski syndrome in a foetus presenting with mildly dysmorphic features
2q23.1 microdeletion of the MBD5 gene in a female with seizures, developmental delay and distinct dysmorphic features
A de novo 163 kb interstitial 1q44 microdeletion in a boy with thin corpus callosum, psychomotor delay and seizures
Delineating the 17q24.2eq24.3 microdeletion syndrome phenotype
A 1 Mb de novo deletion within 11q13.1q13.2 in a boy with mild intellectual disability and minor dysmorphic features
A de novo 3.57 Mb microdeletion in 8q12.3q13.2 in a patient with mild intellectual disability and epilepsy
5p13 microduplication syndrome: A new case and better clinical definition of the syndrome
Blepharophimosis, ptosis, epicanthus inversus syndrome with translocation and deletion at chromosome 3q23 in a black African female
Sporadic male patients with intellectual disability: Contribution of X-chromosome copy number variants
Partial trisomy 1q, region 1q31->qter
Deletion 13q14.3 to q21.32
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