Phenotypic expression of 19q13.32 microdeletions: Report of a new patient and review of the literature

Abstract

The phenotypic manifestations of microdeletions in the 19q13.32 region are still poorly known. In this paper we report a patient who presented with hypotonia, developmental delay, facial dysmorphism, micrognathia, kyphoscoliosis, and buried penis. Chromosomal microarray revealed an interstitial 327 kb de novo microdeletion in the 19q13.32 region comprising eight genes (ARGHAP35, NPAS1, TMEM160, ZC3H4, SAE1, BBC3, MIR3190, and MIR3191). Previously reported cases of microdeletions in the 19q13.32 region were reviewed and compared to our patient, highlighting the common features of a possible 19q13.32 microdeletion syndrome.

Expanding the Clinical Phenotype of 19q Interstitial Deletions: A New Case with 19q13.32-q13.33 Deletion and Short Review of the Literature

“…The authors concluded that the above-mentioned features are common features of 19q13.32 microdeletion syndrome, and that these features result from the deletion of 20–23 genes located in this region, among which are NPAS1, NAPA, ARGHGAP35, DHX34, SLC8A2, ZNF541, and MEIS3, genes that are expressed in the brain parenchyma, glial cells, musculoskeletal system, heart, and gastrointestinal system [ 14 ]. In 2017, Travan et al [ 24 ] described a fifth patient with a 327 kb deletion in this region, consisting of eight genes: ARGHAP35, NPAS1, TMEM160, ZC3H4, SAE1, BBC3, MIR3190, and MIR3191. The patient had hypotonia, facial dysmorphism, micrognathia, developmental delay, kyphoscoliosis, and a buried penis [ 24 ].…”

“…In 2017, Travan et al [ 24 ] described a fifth patient with a 327 kb deletion in this region, consisting of eight genes: ARGHAP35, NPAS1, TMEM160, ZC3H4, SAE1, BBC3, MIR3190, and MIR3191. The patient had hypotonia, facial dysmorphism, micrognathia, developmental delay, kyphoscoliosis, and a buried penis [ 24 ].…”

“…After corroborating the available information in the literature, we can conclude that 19q13 microdeletion syndrome is very complex and, being a contiguous gene syndrome, each case is different even though many features overlap in all patients. We could divide this syndrome into the 19q13.11 microdeletion subgroup, with 14 patients reported so far, according to Abe et al (2018), and the 19q13.32 microdeletion subgroup [ 23 ], with five patients reported so far, according to Castillo and Travan [ 14 , 24 ]. Interestingly, the features overlap, with the exception of cleft palate, right-side aortic arch, and colonic atony, which seem to be related to the 19q13.32 region [ 14 , 24 ].…”

“…We could divide this syndrome into the 19q13.11 microdeletion subgroup, with 14 patients reported so far, according to Abe et al (2018), and the 19q13.32 microdeletion subgroup [ 23 ], with five patients reported so far, according to Castillo and Travan [ 14 , 24 ]. Interestingly, the features overlap, with the exception of cleft palate, right-side aortic arch, and colonic atony, which seem to be related to the 19q13.32 region [ 14 , 24 ]. It is worth mentioning that our patient did not present submucosal cleft palate but had a very high palate.…”

“…Interestingly, her features overlapped the “classical” features of 19q13.11 microdeletion syndrome more. Moreover, our patient presented three features that have, to our knowledge, never been reported so far as being connected to 19q13 microdeletion syndrome, namely, tracheomalacia, iris coloboma, and brain abnormalities consisting of third ventricle enlargement and a subependymal cyst, features that could possibly be specific to the 19q13.32 microdeletion, in which the only brain abnormality mentioned is aplasia of the corpus callosum [ 14 , 24 ].…”