Chromosomal imbalance letterA de novo 7.9 Mb deletion in 22q13.2→qter in a boy with autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings
Section snippets
Methods of detection
Karyotyping by GTG banding of the proband and the parents at 550 bands of resolution and high-resolution comparative genomic hybridization (HR-CGH) analysis of DNA by high-density fine-tiling oligonucleotide array (NimbleGen, Madison, WI, USA) were made. The fine-tiling array-CGH has a manufacture-specified resolution of 2 kb.
Chromosomal anomaly
Conventional karyotyping on 20 metaphase cells was performed and revealed a karyotype of 46,XY,del(22)(q13.2) (Fig. 1). Array-CGH analysis identified a deletion of 22q13.2→qter with the first clone locating at 41,675,914 bp on distal 22q13.2 and the last clone locating at 49,589,250 bp on 22q13.33 according to UCSC Genome Browser on Human Mar. 2006 Assembly (Fig. 2).
Method of confirmation
FISH experiments were performed using BAC clones on metaphase cells. The deletion was confirmed by using probes RP11-91O6 (22q11.21) and RP11-232E17 (22q13.33) (Fig. 3). Polymorphic DNA marker analysis was made to determine parental origin of the deletion.
Causative of the phenotype
The parental karyotypes were normal. Polymorphic DNA marker analysis revealed that the deletion was de novo and of paternal origin.
Clinical description
The 5-year-old boy presented with mental retardation, autistic features, epilepsy, developmental delay and atopic dermatitis. He was born at term with a birth weight of 3497 g as the only child of healthy unrelated parents. The mother was 23 years of age and the father was 32 years of age at the time of his birth. There was no family history of autism, epilepsy and immunological or mental disorders. He was found to have hypotonia and gross motor delay postnatally. When examined at 1 year of
Discussion
We have described a patient with autistic features, developmental delay, epilepsy, language impairment, mental retardation, abnormal immunological findings and atopic dermatitis, carrying a 7.9 Mb de novo deletion of chromosome 22q13.2→qter. The patient manifested characteristic features of chromosome 22q13 deletion syndrome or Phelan-McDermid syndrome (OMIM 606232) which has clinical characteristics including large or unusual ears, relatively large hands, full brow, dolichocephaly, ptosis,
Acknowledgements
This work was supported by research grants NSC-96-2314-B-195-008-MY3 and NSC-97-2314-B-195-006-MY3 from the National Science Council, and MMH-E-98004 from Mackay Memorial Hospital, Taipei, Taiwan.
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Cited by (29)
Genetic syndromes with evidence of immune deficiency
2020, Stiehm's Immune Deficiencies: Inborn Errors of ImmunityProspective longitudinal overnight video-EEG evaluation in Phelan–McDermid Syndrome
2018, Epilepsy and BehaviorCitation Excerpt :In some cases, seizures have been accompanied or preceded by loss of consciousness. Similarly, while there are reports of the EEG findings in this population, the reported EEG features have dramatically varied, including generalized slowing, multifocal slowing, absence or slowing of occipital dominant rhythm, focal and multifocal spike–wave, and sharp wave epileptiform activity [2,18–22]. A recent retrospective analysis of clinically referred, routine EEGs found nonspecific EEG abnormalities in 67% of the cohort (n = 21), despite only 46% having a history of seizures [18].
Late-onset epileptic spasms in a patient with 22q13.3 deletion syndrome
2016, Brain and DevelopmentCitation Excerpt :Detailed information about the manifestation of seizures and EEG characteristics from previous case reports that are available in the literature are provided in Table 1. Generalized tonic-clonic, myoclonic, absence, and focal seizures may occur in patients with 22q13.3 deletion syndrome. [2,4–8]. Soorya et al. reported that 13 of 32 (41%) patients with 22q13.3 deletion syndrome had clinical seizures, including seven (22%) with febrile seizures only, four (13%) with non-febrile seizures, and two (6%) with both febrile and non-febrile seizures [9].
Seizures and EEG pattern in the 22q13.3 deletion syndrome: Clinical report of six Italian cases
2014, SeizureCitation Excerpt :In our sample of patients with 22q13.3 deletion syndrome there is no evidence of a relationship between seizures or EEG abnormalities and developmental impairment. We also found different and aspecific MRI brain abnormalities in our group of patients confirming previous neuroimaging data, such as reduced myelination, agenesia or thinning of corpus callosum, cerebral ventricle dilation, cortical atrophy.6,19,20,23–25 In our series we did not find cerebellar and posterior fossa malformations, namely cerebellar vermis hypoplasia or “mega cisterna magna”, which were observed in 8/10 patients described by Aldinger et al.25 These authors propose PLXNB2 and MAPK8IP2 genes, two genes located in the 22q13 region, as candidates for cerebellar phenotypes.
Genetic Syndromes with Evidence of Immune Deficiency
2014, Stiehm's Immune DeficienciesDistribution of disease-associated copy number variants across distinct disorders of cognitive development
2013, Journal of the American Academy of Child and Adolescent Psychiatry