9p24 triplication in syndromic hydrocephalus with diffuse villous hyperplasia of the choroid plexus

Abstract

Hydrocephalus, a disorder of impaired cerebrospinal fluid (CSF) homeostasis, often results from an imbalance between CSF production and reabsorption. Rarely, hydrocephalus is the consequence of CSF hypersecretion in the context of diffuse villous hyperplasia of the choroid plexus (DVHCP). The limited genetic information in previously reported cases suggests a high prevalence of gains of Chromosome 9p in this disease, although the critical genes involved in DVHCP pathogenesis have not been identified. Here, we report a patient with syndromic hydrocephalus with DVHCP associated with a novel 9p24.3-11.2 triplication and 15q13.2-q13.3 microdeletion. We review the clinical, radiological, and pathological features of DVHCP, as well as its surgical management. A better understanding of the genetic basis of DVHCP could spur the development of rational, targeted nonsurgical hydrocephalus treatments.

Congenital hydrocephalus in a trisomy 9p gained child: a case report

“…Hydrocephalus can be considered as a condition caused by disordered CSF homeostasis that results in expansion of the cerebral ventricles [2,[4][5][6][7]. It may accordingly arise from an increase in CSF secretion and/or an obstruction of flow in the ventricular-subarachnoid pathway, and/or a decrease in drainage to the venous system [2].…”

“…It may accordingly arise from an increase in CSF secretion and/or an obstruction of flow in the ventricular-subarachnoid pathway, and/or a decrease in drainage to the venous system [2]. However, although the choroid plexus with a secretory rate of 0.4 ml minute −1 g tissue −1 is among the most efficient secretory tissues in our body and only paralleled by the cells of the renal proximal tubule and pancreatic ducts, one rarely encounters hydrocephalus caused by CSF hypersecretion [2,4,5]. CSF hypersecretion can be caused by secreting choroid plexus neoplasms (papilloma or carcinoma), which account for 0.4-0.6% of all intracranial neoplasms, or by choroid plexus hyperplasia, where the number of normal productive epithelial cells is increased [4].…”

“…However, although the choroid plexus with a secretory rate of 0.4 ml minute −1 g tissue −1 is among the most efficient secretory tissues in our body and only paralleled by the cells of the renal proximal tubule and pancreatic ducts, one rarely encounters hydrocephalus caused by CSF hypersecretion [2,4,5]. CSF hypersecretion can be caused by secreting choroid plexus neoplasms (papilloma or carcinoma), which account for 0.4-0.6% of all intracranial neoplasms, or by choroid plexus hyperplasia, where the number of normal productive epithelial cells is increased [4]. To date, hydrocephalus caused by choroid plexus hyperplasia has been described in fewer than 30 patients [4][5][6][7]10].…”

“…Hydrocephalus is commonly treated by implantation of a ventriculoperitoneal (VP) shunt). In patients with choroid plexus hyperplasia, however, the CSF production can exceed several liters a day, ultimately causing accumulation of CSF in the abdominal cavity and ascites [1,[4][5][6][7]. Optional but rarely used treatment options such as ventriculoatrial (VA) shunt, choroid plexus coagulation, and pharmacological treatment may thus be needed to control choroid plexus hyperplasia-derived hydrocephalus in trisomy 9p [1, 4-15, 15, 16].…”

“…Optional but rarely used treatment options such as ventriculoatrial (VA) shunt, choroid plexus coagulation, and pharmacological treatment may thus be needed to control choroid plexus hyperplasia-derived hydrocephalus in trisomy 9p [1, 4-15, 15, 16]. However, the known risk of VA shunt-associated cardiovascular complications such as endocarditis, heart failure, intraatrial thrombus, and pulmonary hypertension may exclude this treatment modality in trisomy 9p patients with cooccurring congenital heart disease [4,5,8,9,13,14,16], as illustrated by the current case report.…”