A 46,XY Female with a 9p24.3p24.1 Deletion and a 8q24.11q24.3 Duplication: A Case Report and Review of the Literature

Abstract

Deletion of distal 9p is associated with a rare clinical condition characterized by dysmorphic features, developmental delay, and ambiguous genitalia. The phenotype shows variable expressivity and is related to the size of the deletion. 8q24 duplication has been reported in only few cases to date, all showing dysmorphic features and mild psychomotor developmental delay. A case of chromosomal aberration involving a 9p terminal deletion with an 8q duplication has never been reported. Here, we describe a child with a female phenotype, male karyotype, dysmorphic features, ambiguous genitalia, and developmental delay. In order to assess the cause of the patient's phenotype, conventional karyotyping, FISH, and a chromosomal microarray analysis were performed on the patient and her parents. The cytogenetic and molecular analysis revealed an unbalanced chromosomal aberration with a duplication in the long arm of chromosome 8 at 8q24.11q24.3 associated with a distal deletion in the short arm of chromosome 9 at 9p24.3p24.1, derived from a maternal balanced translocation. We compared the clinical picture of our patient with other similar cases reported in the literature and found that some clinical findings, such as strabismus, symphalangism of the first finger, and cubitus valgus, have never been previously associated with 9p deletion or 8q duplication expanding the phenotypic range of this condition. This study is aimed to better define the clinical history and prognosis of patients with this rare chromosomal aberration.

Fetus of 8q22.2q24.3 duplication and 13q33.2q34 deletion derived from a maternal balanced translocation

“…Among these, TAF2(OMIM: 604912), KCNK9(OMIM: 605847), TRAPPC9(OMIM: 611966), and RECQL4 (OMIM: 603780) have been linked to the intellectual disability, while other genes such as SAMD12(OMIM: 618073), KCNQ3(OMIM: 602232) and GPAA1(OMIM: 603048)have been associated with epilepsy. 9,10 Hence, we speculate that the various malformations of the fetus in ultrasound may be mainly the result of distal deletion in 13q, among which, the cerebellar vermis hypoplasia is a severe abnormality. The 13q terminal deletion is mainly characterized by intellectual disability, developmental delay and congenital anomalies of the brain, such as Dandy-Walker malformation (DWM), corpus callosum agenesis, encephalocele and holoprosencephaly; facial deformity and other disorders, such as bowel atresia and lung hypoplasia.…”

Shared Neurodevelopmental Perturbations Can Lead to Intellectual Disability in Individuals with Distinct Rare Chromosome Duplications

“…ID is caused by perturbations in the significant biological functions that impact cellular networks present in different regions of the CNS. We identified the influence of each of the 44 prioritized genes ( Supplementary Table S5 ) in different tissues and found that these genes are mainly expressed in the CNS when compared with other tissues in humans ( Figure 3 ) [ 14 , 16 , 53 ].…”

“…Moreover, six genes from the duplicated region 18p11.32-p11.21 are highly expressed in several regions of the CNS, from which three of them (LAMA1, MYOM1, and TGIF1) were duplicated in individuals with ID [ 18 , 19 , 20 ]. Furthermore, patients with duplication of 8q24.13q24.3 region involving the KCNQ3, PTK2, ASAP1, and NDRG1 genes, which are widely expressed in CNS, presented ID [ 14 , 16 , 53 ].…”

From karyotypes to precision genomics in 9p deletion and duplication syndromes

“…Genomic data were collected from the literature where approximate breakpoints are known for 53 individuals with 9p deletion and duplication syndromes. 12 , 14 , 15 , 16 , 17 , 19 , 27 , 29 , 30 , 33 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 …”

“… 12 An important phenotype to note that often occurs in individuals with a 9p deletion is sex reversal and other differences in sex development (DSDs). 8 , 12 , 13 , 17 , 24 , 25 , 26 , 27 , 28 , 29 , 30 Ambiguous genitalia are estimated to be present in up to 70% of individuals with 9p deletion. 27 The 46,XY sex reversal phenotype is more commonly found in individuals with terminal 9p deletions than in those with more proximal deletions.…”