Pontine Tegmental Cap Dysplasia: developmental and cognitive outcome in three adolescent patients

Abstract

Pontine Tegmental Cap Dysplasia (PTCD) is a recently described, rare disorder characterized by a peculiar cerebellar and brainstem malformation. Nineteen patients have been reported to date, of which only one in the adolescent age, and data on the clinical, cognitive and behavioural outcome of this syndrome are scarce. Here we describe three adolescent patients with PTCD. All presented bilateral deafness and multiple cranial neuropathies, variably associated with skeletal, cardiac and gastro-intestinal malformations. Feeding and swallowing difficulties, that are often causative of recurrent aspiration pneumonias and death in the first years of life, completely resolved with age in all three patients. Neuropsychological assessment showed borderline to moderate cognitive impairment, with delay in adaptive functioning, visual-spatial and language deficits. Two of three patients also showed mild behavioural problems, although their overall socialization abilities were well preserved. Cochlear implantation in two patients significantly improved their relational and learning abilities. Fibre tractography confirmed the abnormal bundle of transversely oriented fibres forming the typical pontine "tegmental cap" and absence of decussation of the superior cerebellar peduncles, supporting the hypothesis that PTCD results from abnormal axonal guidance and/or migration.These data indicate that PTCD may have a favourable long-term outcome, with borderline cognitive deficit or even normal cognition and partially preserved speech.

Figure 1

Neuroimaging of PTCD patients. MRI and DTI at 1.5 T of patient 1 (A, D, G), patient 2 (B, E) and patient 3 (C, F, H). In all the patients, sagittal T1-weighted images (A, B, C) show the typical "cap" (arrows) in the pontine tegmentum protruding into the fourth ventricle, diagnostic for the malformation. Note also the flat ventral pons and dysplastic cerebellar vermis. T2-weighted images (D, E, F) at the level of the isthmus reveal a "molar tooth-like" appearance, with laterally displaced superior cerebellar peduncles. Colour-coded fractional anisotropy maps of patient 1 (G) and patient 3 (H) are shown with standard DTI conventions (blue for superior↔inferior direction perpendicular to plane of section, red for right↔left direction, green for anterior↔posterior direction). The tegmental "cap" (arrowhead) is a bundle of transversely oriented fibres, possibly representing "ectopic" pontine transverse fibres, normally located in the midpons (double arrowheads in "control").

Figure 2

Tractography study. 3D projection of brainstem tractography (posterior view) at 1.5 T in patient 1 (A), patient 3 (B) and a normal control (C) with 16, 12 and 30 non-collinear diffusion-encoding directions, respectively. In both patients (A, B) the red streamlines of the pontine tegmentum "cap" are clearly visible (arrowhead): some of them continue into the expected location of the middle cerebellar peduncles, possibly representing fibres projecting to the cerebellum. In the normal subject (C), red streamlines (arrowhead) represent the more anteriorly located pontine trasverse fibers, partially "covered" by fibers running longitudinally in the brainstem tegmentum.