Imaging in cutis laxa syndrome caused by a dominant negative ALDH18A1 mutation, with hypotheses for intracranial vascular tortuosity and wide perivascular spaces

- The neuroimaging findings in three children with cutis laxa syndrome based on a dominant negative ALDH18A1 mutation are presented.
- Intracranial vascular tortuosity and wide perivascular spaces were the most notable imaging findings.
- Our data indicate that neuroimaging should be included as part of baseline surveillance.
- We suggest an embryological hypothesis underlying these imaging findings.

The autosomal dominant progeroid form of cutis laxa is a recently identified multiple congenital anomaly disorder characterized by thin, wrinkled skin, a progeroid appearance, intra-uterine growth retardation, postnatal growth restriction, psychomotor developmental delay, microcephaly, cataract, hypotonia and contractures. De novo heterozygous mutations in ALDH18A1 have been described in this condition. We present neuroimaging abnormalities in three patients. One patient had intracranial arterial and venous tortuosity, widened ventricular and extra-axial cerebrospinal fluid (CSF) spaces, wide perivascular spaces and increased T2 signal intensity in the cerebral white matter over time. The second patient had vascular tortuosity. The third patient had prominent ventricular and extra-axial cerebrospinal fluid (CSF) spaces on CT. We propose an embryological mechanism for the development of intracranial vascular tortuosity and discuss the anatomical basis of wide perivascular spaces in relation to this syndrome. Although we do not know the clinical implications of these cerebral vascular anomalies, we suggest inclusion of neuroimaging in the baseline evaluation of these patients.