De novo unbalanced translocation (4p duplication/8p deletion) in a patient with autism, OCD, and overgrowth syndrome

Abstract

Chromosomal abnormalities, such as unbalanced translocations and copy number variants (CNVs), are found in autism spectrum disorders (ASDs) [Sanders et al., 2011]. Many chromosomal abnormalities, including submicroscopic genomic deletions and duplications, are missed by G-banded karyotyping or Fragile X screening alone and are picked up by chromosomal microarrays [Shen et al., 2010]. Translocations involving chromosomes 4 and 8 are possibly the second most frequent translocation in humans and are often undetected in routine cytogenetics [Giglio et al., 2002]. Deletions of 4p16 have been associated with Wolf-Hirschhorn syndrome while 4p16 duplications have been associated with an overgrowth syndrome and mild to moderate mental retardation [Partington et al., 1997]. The 8p23.3 region contains the autism candidate gene DLGAP2, which can contribute to autism when disrupted [Marshall et al., 2008]. There has been a case report of a family with autism spectrum disorder (ASD), prominent obsessional behavior, and overgrowth in patients with der (8) t (4;8) p (16;23) [Partington et al., 1997]. This is an independent report of a male patient with autism, obsessive compulsive disorder (OCD), attention-deficit hyperactivity disorder (ADHD), and an overgrowth syndrome, whose de novo unbalanced translocation der (8) t (4;8) p (16.1→ter ; 23.1→ter) was initially missed by routine cytogenetics but detected with SNP microarray, allowing higher resolution of translocation breakpoints.

Prenatal Diagnosis and Molecular Cytogenetic Characterization of Copy Number Variations on 4p15.2p16.3, Xp22.31, and 12p11.1q11 in a Fetus with Ultrasound Anomalies: A Case Report and Literature Review

“…In our study, the CMA detected a duplication of 4p15.2p16.3 containing the critical 4p16.3 region, the deletion of which was associated with Wolf-Hirschhorn syndrome (WHS; OMIM: 194190), first described in the 1960s [21]. Patients with this deletion usually presented growth impairment, intellectual disability, congenital malformations, distinctive craniofacial appearance, and seizures [22,23].…”

Inherited unbalanced translocation (4p16.3p15.32 duplication/8p23.3p23.2deletion) in the four generation pedigree with intellectual disability/developmental delay

“…A 5-month-old baby with facial deformity, heart defect, and abnormal genitourinary system was too young to exhibit developmental abnormalities [20]. Other patients reported having more severe phenotypes in this study [21]. For example, a 21-year-old male patient had severe neurological developmental disorders.…”

“…Few cases of unbalanced translocation with both chromosome 4 short arm terminal duplication and chromosome 8 short arm terminal deletion have been reported. The recently published literature is summarized in Table 2 [20][21][22]. A 5-month-old baby with facial deformity, heart defect, and abnormal genitourinary system was too young to exhibit developmental abnormalities [20].…”

Subtelomeric Rearrangements: Presentation of 21 Probands with Emphasis on Familial Cases

“…Patient 19 seems to fit better into 4p16.3 duplication characteristics. [20][21][22] Both cases 11 and 12 presented with chromosome 6pter-p24 deletion syndrome, characterized by ID, ophthalmologic abnormalities, craniofacial dysmorphisms (macrocephaly, prominent forehead, down-slanting palpebral fissures, hypertelorism and depressed nasal bridge), Dandy-Walker malformation, congenital heart defects, hypotonia, hearing loss, and others, with high phenotypic variability. 23,24 The father of case 12 presented the same phenotype as his son.…”

“…In the aCGH era, it is tempting to perform only this technique in both children and parents to confirm a de novo occurrence; however, a normal aCGH result does not exclude a balanced translocation in parents, leaving the family at risk for chromosomal imbalances in future pregnancies of 7,8,9,10,11,12,13,14,15,17,18,19,20. For all these cases, written informed consent was given to publish the photographs.…”