Rett Syndrome, Congenital Variant

Alternative Names

  • FOXG1 Syndrome

Associated Genes

Forkhead Box G1
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations of the nervous system

OMIM Number

613454

Mode of Inheritance

Autosomal dominant

Gene Map Locus

14q12

Description

Rett Syndrome, Congenital Variant, also known as FOXG1 syndrome, is a severe neurodevelopmental condition characterized by brain abnormalities and impaired development.  These abnormalities include microcephaly, corpus callosum hypoplasia, delayed myelination, simplified gyral pattern, reduced white matter volume and pachygyria.  This results in severe mental retardation, developmental regression, hypotonia, apraxia, seizures, jerky limb movements, spasticity, dyskinesia, chorea, athetosis and dystonia.  Patients also exhibit limited social skills, with lack of speech development and poor eye contact.  FOXG1 syndrome has an early onset, affecting infants in the first few months of life.  The disorder was initially believed to be a subset of Rett syndrome, but is now recognized as a distinct condition.  Also, FOXG1 syndrome affects both men and women, while Rett syndrome is found almost exclusively in females. Around 100 cases of the disorder have been reported so far.

Diagnosis is done based on clinical features, brain imaging studies and genetic testing.  While there is currently no cure for the disorder, patients may benefit greatly from physical, speech, vision and occupational therapy, nutritional support, orthopedic aids and pharmaceutical agents such as anticonvulsants. 

Molecular Genetics

The disorder is not inherited and instead occurs in isolated cases due to de-novo heterozygous mutations in the FOXG1 gene.  FOXG1 encodes a transcriptional repressor believed to play a key role in the development of the embryonic brain, particularly in the telencephalon region which is responsible for multiple important structures including the cerebrum.  At least 11 mutations within the FOXG1 gene have been reported in people with this syndrome.  Most of these are transitions, transversions or deletions that result in premature truncation of the FOXG1 protein, although some cases are caused by a large deletion in the 14q12 region resulting in the loss of the FOXG1 gene as well as surrounding genes.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
613454.1United Arab EmiratesUnknown Developmental regression; Generalized ...NM_005249.5:c.1397G>AHeterozygousAutosomal, DominantAl-Shamsi et al. 2016
613454.2Saudi ArabiaFemaleNoYes Protruding ear; Prominent nasal tip; Wid...NM_005249.5:c.689G>THeterozygousAutosomal, DominantShaheen et al. 2019
617360.1United Arab EmiratesFemale Microcephaly; Strabismus; Visual impairm...NM_005249.5:c.256delHeterozygousAutosomal, DominantTrinh et al. 2019 Patient had dual dia...
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