Schif Aharon, Ekchilevitch Nina, Daver Ruthy, Shahar Eli
In order to refine the FOXG1 duplication syndrome phenotype we have performed a review of the clinical picture of 14 patients reported to date in the literature, adding a new personal 15th case.
Deletions and inactivating mutations of FOXG1 have been associated
with a Rett-like syndrome characterized by hypotonia, irritability, developmental delay, hand stereotypies, and deceleration of head growth. FOXG1, has an important role in the developing brain.
FOX G1 Duplication syndrome that include a 14q12 duplication encompassing FOXG1 gene -have been recently associated with developmental delay, speech impairment, epilepsy, aspecific neuroimaging findings and minor dimorphisms.
Chromosomal micro array (CMA) test was performed using peripheral blood cells from our proband patient using standard techniques.
we have performed a review of the phenotypic clinical picture of the patients
reported to date in the literature.
A 17.4 Mb duplication at 14q11.2-q21.1 including FOXG1gene was detected in our 24 month old female patient presented by 4 month with global developmental delay, speech impairment, early treatable infantile spasms, hypotony, and mild dimorphism. Deceleration of head growth since birth was found but without microcephaly and without developmental regression.
We found 6 other reports describing a total of 14 patients of both sexes with 14q12 duplications of varying sizes. 2/3 of patients including ours (10/15 patients) developed seizures –mainly infantile spasms (9/10 epileptic patients) – in the first months of life (10/10 epileptic patients). Developmental delay or mental retardation was reported in 2/3 (10/15 patients). With available follow up, 6/10 patients were seizure free with or without therapy. Mild dimorphism was reported in 6/15 patients. Deceleration of head growth was reported in 3/15 patients Independent walking was reported in 9/15 patients.
Patients presenting with early epileptic encephalopathy mainly infantile spasms developmental delay and sometimes with mild dimorphism, should be screened for FOXG1 duplication syndrome by CMA testing.