Unusual Combination of MEN-1 and the Contiguous Gene Deletion Syndrome of CAH and Ehlers-Danlos Syndrome (CAH-X)

Abstract

The contiguous gene deletion syndrome of congenital adrenal hyperplasia and Ehlers-Danlos syndrome, named CAH-X, is a rare entity that occurs because of a deletion of a chromosomal area containing 2 neighboring genes, TNXB and CYP21A. Here, we describe a patient from a consanguineous family in which coincidentally MEN-1 syndrome is associated with CAH-X, causing particular challenges explaining the phenotypic features of the patient. A 33-year-old man with salt-wasting congenital adrenal hyperplasia and classic-like Ehlers-Danlos syndrome presented with an adrenal crisis with a history of recurrent hypoglycemia, abdominal pain, and vomiting. He was found to have primary hyperparathyroidism, hyperprolactinemia, and pancreatic neuroendocrine tumors, as well as primary hypogonadism, large adrenal myelolipomas, and low bone mineral density. A bladder diverticulum was incidentally found. Genetic analysis revealed a heterozygous previously well-described MEN1 mutation (c.784-9G > A), a homozygous complete deletion of CYP21A2 (c.1-?_1488+? del), as well as a large deletion of the neighboring TNXB gene (c.11381-?_11524+?). The deletion includes the complete CYP21A2 gene and exons 35 through 44 of the TNXB gene. CGH array found 12% homozygosity over the whole genome. This rare case illustrates a complex clinical scenario with some initial diagnostic challenges.

Bladder diverticulum accompanied by abdominal pain: a case description

“…There are two types of bladder diverticula: congenital and acquired. Congenital bladder diverticula are relatively rare ( 3 ). Acquired bladder diverticula are most often caused by a block in the bladder outlet, which results in increased intravesical pressure in the bladder ( 4 ).…”

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance

“…At a lower level of statistical evidence, we mention the sample-focused analysis of case reports with regard to the parathyroid and pancreatic MEN1-NETs having a specified genetic confirmation of the MEN1 pathogenic variant (regardless of if the type was detailed by the original authors) [68,73,75,77,81,97,100,[116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132] (Table 6). There were 24 MEN1 subjects (including index cases with genetic analysis for their relatives) within 24 papers; they were aged between 17 years (only two pediatric cases were found) and 74 years; the female-to-male ratio was 0.84.…”

“…At a lower level of statistical evidence, we mention the sample-focused analysis of case reports with regard to the parathyroid and pancreatic MEN1-NETs having a specified genetic confirmation of the MEN1 pathogenic variant (regardless of if the type was detailed by the original authors) [ 68 , 73 , 75 , 77 , 81 , 97 , 100 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ] ( Table 6 ).…”

“…There were 24 MEN1 subjects (including index cases with genetic analysis for their relatives) within 24 papers; they were aged between 17 years (only two pediatric cases were found) and 74 years; the female-to-male ratio was 0.84. The female population (N = 11) had an average age of 43.63 years (ranges between 28 and 60); males (N = 13) had a mean age of 40.07 years (ranges between 17 and 74) [ 68 , 73 , 75 , 77 , 81 , 97 , 100 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 ].…”

“…del) and a large deletion of the neighboring TNXB gene (c.11381-?_11524+?) in exons 35 to 44 that involved a phenotype with salt-wasting congenital adrenal hyperplasia (complicated with adrenal crisis during adulthood) and features of classic-like Ehlers–Danlos syndrome [ 131 ].…”