Multiple cysts of the corpus callosum and psychomotor delay in a patient with a 3.1 Mb 15q24.1q24.2 interstitial deletion identified by array‐CGH

Chromosome 15q24 microdeletion syndrome is a recently described rare microdeletion syndrome that has been reported in 19 individuals. It is characterized by growth retardation, intellectual disability, and distinct facial features including long face with high anterior hairline, hypertelorism, epicanthal folds, downslanting palpebral fissures, sparse and broad medial eyebrows, broad and/or depressed nasal bridge, small mouth, long smooth philtrum, and full lower lip. Other common findings include skeletal and digital abnormalities, genital abnormalities in males, hypotonia, behavior problems, recurrent infections, and eye problems. Other less frequent findings include hearing loss, growth hormone deficiency, hernias, and obesity. Congenital malformations, while rare, can be severe and include structural brain anomalies, cardiovascular malformations, congenital diaphragmatic hernia, intestinal atresia, imperforate anus, and myelomeningocele. Karyotypes are typically normal, and the deletions were detected in these individuals by array comparative genomic hybridization (aCGH). The deletions range in size from 1.7-6.1 Mb and usually result from nonallelic homologous recombination (NAHR) between paralogous low-copy repeats (LCRs). The majority of 15q24 deletions have breakpoints that localize to one of five LCR clusters labeled LCR15q24A, -B, -C, -D, and -E. The smallest region of overlap (SRO) spans a 1.2 Mb region between LCR15q24B to LCR15q24C. There are several candidate genes within the SRO, including CYP11A1, SEMA7A, CPLX3, ARID3B, STRA6, SIN3A and CSK, that may predispose to many of the clinical features observed in individuals with 15q24 deletion syndrome. The deletion occurred as a de novo event in all of the individuals when parents were available for testing. Parental aCGH and/or FISH studies are recommended to provide accurate genetic counseling and guidance regarding prognosis, recurrence risk, and reproductive options. Management involves a multi-disciplinary approach to care with the primary care physician and clinical geneticist playing a crucial role in providing appropriate screening, surveillance, and care for individuals with this syndrome. At the time of diagnosis, individuals should receive baseline echocardiograms, audiologic, ophthalmologic, and developmental assessments. Growth and feeding should be closely monitored. Other specialists that may be involved in the care of individuals with 15q24 deletion syndrome include immunology, endocrine, orthopedics, neurology, and urology. Chromosome 15q24 microdeletion syndrome should be differentiated from other genetic syndromes, particularly velo-cardio-facial syndrome (22q11.2 deletion syndrome), Prader-Willi syndrome, and Noonan syndrome. These conditions share some phenotypic similarity to 15q24 deletion syndrome yet have characteristic features specific to each of them that allows the clinician to distinguish between them. Molecular genetic testing and/or aCGH will be able to diagnose these conditions in the majority of individuals.Disease name a...

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“…Other features that have been reported in a minority of cases include strabismus [1-3,6,10] nystagmus [1,5,8] and dental abnormalities [1]. …”

Section: Clinical Descriptionmentioning

confidence: 99%

Chromosome 15q24 microdeletion syndrome

Magoulas

El‐Hattab

2012

Orphanet J Rare Dis

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“…28 El-Hattab et al 22 Van Esch et al 20 Klopocki et al 19 Sharp et al 7 Case 1 Masurel-Paulet et al 21 Case 1 Foot deformities include clubfeet, pes planus, or pes cavus. M, male; F, female; MR/DD, mental retardation and/or developmental delay; IUGR, intrauterine growth restriction; CC, corpus callosum; VSD, ventricular septal defect; ADHD, attention-deficit hyperactivity disorder; GH, growth hormone; ALL, acute lymphoblastic leukemia; MMC, myelomeningocele.…”

Section: Cytogenetic and Fluorescence In Situ Hybridization Analysesmentioning

confidence: 99%

Deletion and duplication of 15q24: Molecular mechanisms and potential modification by additional copy number variants

El‐Hattab

Zhang

Maxim

et al. 2010

Genetics in Medicine

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Purpose: To investigate the potential influence of additional copy number variants in patients with 15q24 rearrangements and the possible underlying mechanisms for these rearrangements. Methods: Oligonucleotide-based chromosomal microarray analyses were performed, and the results were subsequently confirmed by fluorescence in situ hybridization analyses. Long-range polymerase chain reaction amplification and DNA sequencing analysis were used for breakpoint junction sequencing. Results: We describe a 15-year-old boy with cognitive impairment and dysmorphic features with deletions in 15q24 and 3q21, a 2-month-old female infant with growth deficiency, heterotaxy, cardiovascular malformations, intestinal atresia, and duplications in 15q24 and 16q22, and a 3.5-year-old boy with developmental delay, microcephaly, and dysmorphic features, with duplications in 15q24 and 2q36.3q37.1. Breakpoint sequencing for the 15q24 deletion in the first patient revealed microhomology and suggested the underlying mechanism of either nonhomologous end joining or fork stalling and template switching/microhomology-mediated break-induced replication. Conclusions: The three described patients with 15q24 rearrangements have copy number variants at other loci and exhibit additional clinical features with a more severe phenotype than that observed in previously reported patients with isolated 15q24 rearrangements, suggesting that the genomic mutational load may contribute to the phenotypic severity and variability in patients with 15q24 rearrangements. Genet Med 2010:12(9):573-586.

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“…To date there are 18 reported cases involving 15q24.1 deletion which are detected by array-based methods (Andrieux et al, 2009;El-Hattab et al, 2009;El-Hattab et al, 2010;Klopocki et al, 2008;Marshall et al, 2008;Masurel-Paulet et al, 2009;McInnes et al, 2010;Sharp et al, 2007;Van Esch et al, 2009). The sizes of the deleted regions range from 1.7 Mb to 6.1 Mb.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, a new breakpoint region (BP4) centromeric to BP1 was identified (Masurel-Paulet et al, 2009). The proximal breakpoint of the deletion in our case appears to coincide with BP4, while the distal breakpoint is within BP3.…”

Section: Resultsmentioning

confidence: 99%

An Additional Case of the Recurrent 15q24.1 Microdeletion Syndrome and Review of the Literature

Chin

Lim

et al. 2011

Twin Res Hum Genet

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We report a 9-year-old girl with 3 Mb interstitial deletion of chromosome 15q24 identified by oligonucleotide array comparative hybridization. She is of Chinese ancestry and shared some typical features of previously reported 15q24 deletion cases such as mild dysmorphism with developmental and speech delay. She also had mild hearing loss that was reported in one other case. We compared all 19 cases that are identified from array-CGH. The deletion occurred within an 8.3 Mb region from 15q23 to 15q24.3. The minimum overlapping deleted region is less than 0.5 Mb from 72.3 Mb to 72.7 Mb. The functions of the nine annotated genes within the region and how they might contribute to the microdeletion phenotype are discussed.

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Multiple cysts of the corpus callosum and psychomotor delay in a patient with a 3.1 Mb 15q24.1q24.2 interstitial deletion identified by array‐CGH

Cited by 21 publications

References 14 publications

Chromosome 15q24 microdeletion syndrome

Chromosome 15q24 microdeletion syndrome

Deletion and duplication of 15q24: Molecular mechanisms and potential modification by additional copy number variants

An Additional Case of the Recurrent 15q24.1 Microdeletion Syndrome and Review of the Literature

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