An Adolescent with a Rare De Novo Distal Trisomy 6p and Distal Monosomy 6q Chromosomal Combination

We report on a 12-year-old female with both a partial duplication and deletion involving chromosome 6. The duplication involves 6p25.3p24.3 (7.585 Mb) while the deletion includes 6q27q27 (6.244 Mb). This chromosomal abnormality is also described as distal trisomy 6p and distal monosomy 6q. The patient has a Chiari II malformation, hydrocephalus, agenesis of the corpus callosum, microcephaly, bilateral renal duplicated collecting system, scoliosis, and myelomeningocele associated with a neurogenic bladder and bladder reflux. Additional features have included seizures, feeding dysfunction, failure to thrive, sleep apnea, global developmental delay, intellectual disability, and absent speech. To our knowledge, our report is just the sixth case in the literature with concomitant distal 6p duplication and distal 6q deletion. Although a majority of chromosomal duplication-deletion cases have resulted from a parental pericentric inversion, the parents of our case have normal chromosomes. This is the first reported de novo case of distal 6p duplication and distal 6q deletion. Alternate explanations for the origin of the patient’s chromosome abnormalities include parental gonadal mosaicism, nonallelic homologous recombination, or potentially intrachromosomal transposition of the telomeres of chromosome 6. Nonpaternity was considered but ruled out by whole exome sequencing analysis.

Eosinophilic esophagitis: pathophysiology and its clinical implications

Classically, eosinophilic esophagitis is an antigen-mediated chronic disease distinct from gastroesophageal reflux disease. Eosinophilic esophagitis is an emerging clinical problem that is growing in recognition. It is characterized clinically by feeding dysfunction, dysphagia, and reflux-like symptoms. Histologically, eosinophilic esophagitis is identifiable by a dense epithelial eosinophilic infiltrate. Experimental modeling and clinical studies over the last decade have greatly improved mechanistic insights and led to improvements in clinical understanding and the assessment of therapeutic options for patients and their clinicians who manage this disease. Here, we review the clinicopathologic diagnostic criteria and our understanding of eosinophilic esophagitis as an allergic disease with genetic and immunological components. We present studies defining the importance of the epithelial barrier and the concept of barrier dysfunction as an initiating or perpetuating factor for this disease. We discuss the relationship between the symptoms of dysphagia and feeding dysfunction, our current knowledge of the underlying pathophysiologic mechanisms, and advances in clinical assessment of esophageal distensibility and narrowing in eosinophilic esophagitis patients. Finally, therapeutic implications relating to the advances that have led to our current understanding of the pathophysiology of eosinophilic esophagitis are explored.