Novel Case of 9p- Deletion in a Patient with Cardiac Pathology and a Review of the Literature

Our case focuses on a patient with a rare mutation, 9pter-9p22.2 interstitial deletion, associated with unique presentation and specific cardiac abnormalities which have not previously been associated with this condition. The subject was a term male infant born with an omphalocele which had been diagnosed prenatally. Upon delivery he was noted to have craniofacial and limb abnormalities, and found to be persistently hypoglycemic, requiring a significantly elevated glucose infusion rate. On echocardiogram an aortic coarctation was identified. He underwent cardiac repair, but ultimately developed severe pulmonary hypertension complicated by multiple episodes of cardiopulmonary arrest. To our knowledge there are only 26 previously identified patients with similar copy number variants on this region reprinted in the literature or identified in the Decipher database. This case report is not only able to help build knowledge which can be used to predict phenotypes, but it can also shed light on some of the more devastating characteristics possible with this condition. While this subject did have two of the most common symptoms involved, craniofacial and musculoskeletal, he also had cardiovascular abnormalities, which had only been identified in one other patient with 9pter-9p22.2 interstitial deletion. It was also a goal of this report to identify similarities and differences between 9pter-9p22.2 interstitial deletion with the much more well-known disease, 9p minus syndrome. Of patients with 9p minus, craniofacial and musculoskeletal abnormalities are very common. Patients also frequently have visceral defects, intellectual disabilities, hypoglycemia, genital defects, and a small incidence of cardiovascular defects. More subjects are needed for further evaluation, but it appears that 9pter-9p22.2 interstitial deletion may be much more similar to the larger 9p minus syndrome than previously appreciated. Introduction/Background Current advancements in pediatric critical care as well as the evolution of human genomic investigations have revealed a wide range of clinical pathologies warranting further classification and, inturn, clinical correlations by providers. The DECIPHER database has focused on cataloguing specific mutations with correlated phenotypes to better characterize genetic abnormalities [1]. 9p deletion syndrome is a pathologic genetic copy number variant initially identified in 1973 by Alfi and colleagues [2]. Since this time, more than 100 cases of 9p minus have been reported worldwide. The syndrome represents a heterogeneous condition, characterized upon initial presentation with craniofacial abnormalities (including trigonocephaly, midface hypoplasia, upslanting palpebral fissures, anteverted nostrils, depressed nasal bridge, long philtrum, and hypertelorism), short neck, increased inter-nipple distance, positional limb defects, nonketotic hypoglycemia, external genitalia anomalies, and cardiac abnormalities [3]. Follow up and longitudinal assessments demonstrate neurocognitive difficulties including low IQ (mean of 49), global developmental delays, hypotonia, and behavioral problems [4]. Visceral abnormalities including inguinal or umbilical hernias and omphaloceles have also been reported [5,6]. Swinkels et al. previously observed approximately 15% of patients with 9psyndrome had an omphalocele [7]. More specifically, 9pter-9p22.2 interstitial deletion, is a microdeletion syndrome which has demonstrated an emerging clinical significance and has currently been diagnosed in 26 patients across the globe. As shown in Table 1, these patients share many phenotypic similarities to 9pminus, but 9pter-9p22.2 interstitial deletion is subtyped with an even stronger association with craniofacial deformities and developmental delays [8]. With the apparent rise in the frequency of 9pminus diagnosis and concomitant presentations of the 9pter-9p22.2 interstitial deletion subtype, our report serves to catalogue and summarize the available data to provide initial diagnosing providers and follow up clinicians with a more robust clinical picture to best manage these complex patients. Koslow E (2018) Novel Case of 9pDeletion in a Patient with Cardiac Pathology and a Review of the Literature J Clin Res Med, Volume 1(2): 2–3, 2018 Table 1. Phenotypic abnormalities in known patients with 9pter-9p22.2 interstitial deletion [8]. Phenotypic Abnormality Number with abnormality (N = 26) % with abnormality Head, ears, eyes, nose, throat 10 38.5 Developmental 10 38.5 Musculoskeletal 6 23.1