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Posterior fossa malformations in TASP1-related disorder (Suleiman-El-Hattab Syndrome)

Objectives: Homozygous loss-of-function variants in TASP1 have been associated with Suleiman-El-Hattab syndrome, a newly described neurodevelopmental disorder. We aim to study four individuals with Suleiman-El-Hattab syndrome, who had cystic malformations in the posterior fossa on cranial imaging. Methods: Patients’ demographic, clinical and imaging features were studied. Genetic testing including chromosomal microarray and/or exome sequencing were performed for all individuals. Results: The four cases (2 females), aged nine months to ten years, had biallelic TASP1 loss-of-function variants. They all had a neurodevelopmental disorder characterised by developmental delay, distinctive facial appearance, and happy demeanor. All had cardiac malformations; mostly mild PFO/VSD with spontaneous resolution, however; one individual (case1) had severe cardiac malformation (TOF) and required surgery (Table 1). All individuals had cystic malformations of the posterior fossa, varying from small cerebellopontine angle arachnoid cyst to dilated 4th ventricle with enlarged posterior fossa along with cerebellar vermian hypoplasia, to the full extent of classic Dandy Walker malformation with hydrocephalus (Figure 1). Conclusion: This work sheds more light and further delineates Suleiman-El-Hattab syndrome. In addition to the neurodevelopmental and distinctive facial features, posterior fossa cystic malformations seem to be an additional feature in some patients with this syndrome (which has not been previously reported). This extends the neurologic phenotype of Suleiman-El-Hattab syndrome, and might help neurologists and radiologists to recognise this syndrome. In addition, this supports the notion that imaging findings of cerebellar hypoplasia and Dandy Walker malformation are often associated with underlying genetic causes and should prompt further evaluation.