In FOXP2-plus-related disorders oral motor deficits, global developmental delay, and autism spectrum disorder are common. Īllopurinol is widely prescribed for the treatment of hyperuricemia and gout. Autistic features and dysmorphic findings have been reported in a few affected individuals. Fine motor skills may be impaired (e.g., buttoning clothes, tying shoelaces), yet gross motor skills are normal. In FOXP2-only-related disorders, nonverbal (performance) IQ is typically more preserved compared to verbal IQ. The genetic alteration determines if only speech and language problems are present (FOXP2-only-related speech and language disorder) or if more global developmental and behavioral issues are likely to be present as well (FOXP2-plus-related speech and language disorder). The underlying genetic cause of FOXP2-related speech and language disorders is either disruption of FOXP2 only (referred to in this GeneReview as FOXP2-only-related speech and language disorder) or large copy number variants (i.e., contiguous gene deletions), structural variants (i.e., chromosome translocation or inversion), or maternal uniparental disomy of chromosome 7 (UPD7) involving FOXP2 (here referred to as FOXP2-plus-related speech and language disorders). Additional findings in FOXP2-related speech and language disorders can include oral motor dyspraxia (difficulty planning or programming oral movements on command) dysarthria (a neuromuscular-based speech disorder that may affect nasal resonance, voice quality, prosody, and breath support for speech) moderate to severe receptive and expressive language disorder and reading and spelling impairments. All individuals with CAS – whether caused by an alteration of FOXP2 or of an unknown cause – have difficulties in automatically and accurately sequencing speech sounds into syllables, syllables into words, and words into sentences with the correct prosody.
Somatic mutation, disruption, or copy number variation of the following genes or loci may also contribute to the formation of glioma: ERBB (EGFR 131550), ERBB2 (164870), LGI1 (604619), GAS41 (602116), GLI (165220), DMBT1 (601969), IDH1 (147700), IDH2 (147650), BRAF (164757), PARK2 (602544), TP53 (191170), RB1 (614041), PIK3CA (171834), 10p15, 19q, and 17p13.3. Īll FOXP2-related speech and language disorders, regardless of the underlying genetic alteration, have a core phenotype: childhood apraxia of speech (CAS), a disorder of speech motor programming or planning that affects the production, sequencing, timing, and stress of sounds, syllables, and words. Genetic Heterogeneity of Susceptibility to Glioma Other glioma susceptibilities include GLM2 (613028), caused by variation in the PTEN gene (601728) on chromosome 10q23 GLM3 (613029), caused by variation in the BRCA2 gene (600185) on chromosome 13q13 GLM4 (607248), mapped to chromosome 15q23-q26.3 GLM5 (613030), mapped to chromosome 9p21 GLM6 (613031), mapped to chromosome 20q13 GLM7 (613032), mapped to chromosome 8q24 GLM8 (613033), mapped to chromosome 5p15 and GLM9, caused by variation in the POT1 gene (606478) on chromosome 7q31. Familial clustering of gliomas may occur in the absence of these tumor syndromes, however. Gliomas are known to occur in association with several other well-defined hereditary tumor syndromes such as mismatch repair cancer syndrome (see 276300), melanoma-astrocytoma syndrome (155755), neurofibromatosis-1 (NF1 162200) and neurofibromatosis-2 (see SWNV, 101000), and tuberous sclerosis (TSC1 191100). They tend to be slow-growing, noninvasive, and located in the ventricular system, septum pellucidum, cerebral aqueduct, or proximal spinal cord (summary by Ryken et al., 1994). They were characterized as a distinct entity by Scheinker (1945). Subependymomas are unusual tumors believed to arise from the bipotential subependymal cell, which normally differentiates into either ependymal cells or astrocytes. Ependymomas are rare glial tumors of the brain and spinal cord (Yokota et al., 2003). Glial cells can show various degrees of differentiation even within the same tumor (summary by Kyritsis et al., 2010). Gliomas are central nervous system neoplasms derived from glial cells and comprise astrocytomas, glioblastoma multiforme, oligodendrogliomas, ependymomas, and subependymomas.
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