Infantile Spasms in a Patient with Williams Syndrome and Craniosynostosis

Abstract

Summary: A patient with Williams syndrome, craniosynostosis, and infantile spasms is described. At age 6 months, the infant demonstrated infantile spasms and craniosynostosis and was operated on for craniosynostosis and treated with adrenocorticotropic hormone (ACTH) for the infantile spasms. ACTH completely controlled the seizures, but was halted because of the progression of ventricular hypertrophy. The seizure returned, and he was found to have elfin face, failure‐to‐thrive, developmental delay, and dental malformation in addition to congenital heart defects. High‐resolution chromosome analysis revealed interstitial deletion of 7q11.22‐q11.23. Therefore his clinical and cytogenetic diagnosis was Williams syndrome. Thyrotropin‐releasing hormone (TRH) therapy reduced his seizures and improved the findings of EEG without cardiac side effects. In addition, his psychomotor development was slightly improved.

Zebrafish gene knockdowns imply roles for human YWHAG in infantile spasms and cardiomegaly

“…The range of this deletion is exactly same as that of the patient reported by Morimoto et al who also showed infantile spasms and cardiomegaly (Morimoto et al, 2003) (see Fig. 5).…”

“…This indicates that the infantile spasms and the cardiomegaly observed in patient 2 might be derived from haploinsufficiency of YWHAG, because the WBS patient reported by Morimoto et al (2003). also showed infantile spasms and cardiomegaly.…”

“…Marshall et al (2008) investigated 16 patients associated with documented seizures and interstitial deletions of 7q11.23-q21.1, which is neighboring to the WBS critical region, and revealed overlapping deletions of the MAGI2 in most patients. However, they reported at least one patient having infantile spasms and a chromosomal deletion including WBS critical region but in which MAGI2 was not included, who had been reported previously by Morimoto et al (2003).…”

“…WBS patients with common deletions rarely have epilepsy, especially infantile spasms. Until now, only a few WBS patients with infantile spasms have been reported (Mizugishi et al, 1998;Morimoto et al, 2003). In 2008, Marshall et al reported 28 patients with infantile spasms, twenty of whom had deletion of 7q11.23, the WBS critical region, and eight of whom had deletion of 7q21.…”

De Novo Mutations in YWHAG Cause Early-Onset Epilepsy

“…Three genes-MAGI2 (MIM: 606382), HIP1 (MIM: 601767), and YWHAGhave been suggested as possible candidates for these atypical features. [46][47][48][49][50][51][52][53] Ramocki et al 51 suggested that haploinsufficiency of HIP1 is sufficient to alter neuronal homeostasis and cause focal and generalized epilepsies and cognitive dysfunction. However, their findings do not exclude the possibility that YWHAG loss of function is sufficient to cause neurological phenotypes alone, as proven by our results.…”