International Clinical Neuroscience Journal

Vol. 12 No. Continuous (2025)

FOXG1 Syndrome: Unraveling Congenital Rett-Like Disorder FOXG1 Syndrome

International Clinical Neuroscience Journal, Vol. 12 No. Continuous (2025), 25 January 2026 , Page e5
https://doi.org/10.22037/icnj.v12i1.50806

Abstract

FOXG1 syndrome is a rare neurodevelopmental disorder caused by mutations in the FOXG1 gene, leading to severe developmental delay, microcephaly, movement disorders, epilepsy, and autistic features. Though it shares some phenotypic similarities with Rett syndrome, it has a distinct genetic etiology and clinical course. We report a 1-year-old 3-month-old boy, the second-born child of a non-consanguineous couple, who presented with recurrent seizures from 4 months of age, characterized by infantile spasms. The child exhibited global developmental delay, poor social interaction, irritability, and sleep disturbances. Clinical examination revealed microcephaly, hypotonia, exaggerated deep tendon reflexes, and extensor plantar responses. Neuroimaging showed benign enlargement of the subarachnoid space, and genetic testing confirmed a pathogenic FOXG1 mutation. Despite multiple anti-seizure medications, the child’s epilepsy remained refractory. He is currently being managed on a ketogenic diet, anti-epileptic medication, and intensive multidisciplinary therapy sessions. This case highlights the diagnostic challenges of FOXG1 syndrome and its overlapping but distinct features from Rett syndrome. The patient’s refractory epilepsy, severe developmental delay, and poor response to conventional therapies align with existing literature. Neuroimaging findings in these patients are varied. This syndrome has a poor prognosis, with no definitive treatment available at present. FOXG1 syndrome is a distinct entity requiring early diagnosis and multidisciplinary management. Further research into gene-targeted therapies is crucial for improving outcomes.

Keywords:
  • FOXG1 gene mutation; developmental delay; Congenital Rett-Like Disorder; neurodevelopmental disorder

How to Cite

1.
Balakumaran P, Jeet Daniel N, Rajan N, Kumar Kommu PP. FOXG1 Syndrome: Unraveling Congenital Rett-Like Disorder: FOXG1 Syndrome. Int Clin Neurosci J [Internet]. 2026 May 4 [cited 2026 Jul. 5];12(Continuous):e5. Available from: https://journals.sbmu.ac.ir/neuroscience/article/view/50806

References

1. Ariani F, Hayek G, Rondinella D, Artuso R, Mencarelli MA, Spanhol-Rosseto A, et al. FOXG1 mutations cause the congenital variant of Rett syndrome. Am J Hum Genet. 2008;83(1):89–93. doi: 10.1016/j.ajhg.2008.06.007

2. Mitter D, Reichel K, Schröder S, Laccone F, Klink B, Bähring S, et al. FOXG1 syndrome: Genotype–phenotype association in 83 patients with FOXG1 variants. Genet Med. 2018;20(1):98–108. doi: 10.1038/gim.2017.75

3. Kortüm F, Das S, Flindt M, Morris-Rosendahl DJ, Stefanova I, Goldstein A, et al. The spectrum of FOXG1 syndrome: Severe epileptic encephalopathy and bilateral polymicrogyria. Brain. 2011;134(7):2443–51. doi: 10.1093/brain/awr168

4. Vegas N, Cavallin M, Maillard C, Boddaert N, Toulouse J, Schaefer E, et al. Delineating FOXG1 syndrome: From congenital microcephaly to Rett-like neurodevelopmental disorders. J Med Genet. 2018;55(4):256–63. doi: 10.1136/jmedgenet-2017-104805

5. Striano P, Battaglia S, Giordano L, Paravidino R, Ferrari AR, Gaggero R, et al. Clinical and genetic characterization of FOXG1 syndrome in epileptic encephalopathy patients. Epilepsy Res. 2017;135:16–23. doi: 10.1016/j.eplepsyres.2017.05.006

6. Tully HM, Dobyns WB. Infantile spasm and early epileptic encephalopathy in patients with FOXG1 mutations. Neurology. 2015;84(9):834–841. doi: 10.1212/WNL.0000000000001292

7. Paciorkowski AR, Thio LL, Rosenfeld JA, Gajecka M, Czapanskiy R, Kline AD, et al. FOXG1-related disorders: Clinical diagnosis, genetic testing, and therapeutic considerations. Pediatr Neurol. 2019;97:50–58. doi: 10.1016/j.pediatrneurol.2019.04.012

8. Wong LC, Wuu J, Hsu CJ, Cheng SY, Lee WT, Wang HS, et al. Clinical and sleep manifestations in children with FOXG1 syndrome. Sleep Med. 2022;90:136–144. doi: 10.1016/j.sleep.2021.12.020

9. Mueller K, Shine MG, Lee J, et al. The emerging face of FOXG1 syndrome: A rare, genetically defined neurodevelopmental disorder coming of age in the genomics era. Orphanet J Rare Dis. 2021;16(1):117. doi: 10.1186/s13023-021-01778-5

10. Striano P, Curry CJ, Maljevic S, et al. Clinical and genetic characterization of FOXG1 syndrome in epileptic encephalopathy patients. Epilepsy Res. 2017;135:16–23. doi: 10.1016/j.eplepsyres.2017.05.006

  • Abstract Viewed: 73 times
  • PDF Downloaded: 35 times

Download Statastics