| Topic | Summary | Publication / year | PMID / identifier(s) | URL | Citation |
|---|---|---|---|---|---|
| Disease names / synonyms / identifiers | Evidence supports the SRPX2-associated disease spectrum including **Rolandic epilepsy–speech dyspraxia** / **RESDX** / **rolandic epilepsy-speech dyspraxia syndrome** and **bilateral perisylvian polymicrogyria (BPP)** / **congenital bilateral perisylvian syndrome**. OMIM numbers explicitly mentioned for **SRPX2 (OMIM 300642)**, **Rolandic epilepsy–speech dyspraxia (OMIM 300643)**, and **bilateral perisylvian polymicrogyria (OMIM 300388)**. Open Targets context lists **MONDO_0015587 rolandic epilepsy-speech dyspraxia syndrome** and **Orphanet 163721 Rolandic epilepsy - speech dyspraxia**. | Hum Mol Genet 2010; Open Targets context; IJMS review 2024 | PMID not shown in context for 2010 paper; MONDO_0015587; Orphanet 163721; OMIM 300642/300643/300388 | https://doi.org/10.1093/hmg/ddq415 | (pqac-00000003, pqac-00000000, pqac-00000013) |
| Inheritance | Reported as an **X-linked** syndrome for SRPX2-related RESDX; females may show milder or variable manifestations, plausibly influenced by skewed X-inactivation. PMG literature notes familial PMG can be autosomal dominant, autosomal recessive, or X-linked, but the SRPX2 disorder specifically is X-linked in the cited syndrome reports. | Epilepsia 2009; IJMS review 2024; PMG review 2022 | PMID not shown in context | https://doi.org/10.1111/j.1528-1167.2009.02214.x ; https://doi.org/10.3390/ijms25074110 ; https://doi.org/10.4103/aian.aian_97_22 | (pqac-00000009, pqac-00000013, pqac-00000015) |
| Core phenotype: speech / oromotor | Recurrent phenotypes across reports/reviews include **speech delay**, **verbal/oral dyspraxia**, **oro-facial dyspraxia**, and language-cortex dysfunction. These features are central to the named syndrome and often accompany epilepsy; intellectual disability may be variable. | Epilepsia 2009; IJMS review 2024 | PMID not shown in context | https://doi.org/10.1111/j.1528-1167.2009.02214.x ; https://doi.org/10.3390/ijms25074110 | (pqac-00000009, pqac-00000013) |
| Core phenotype: epilepsy | Seizures are typically **rolandic/centrotemporal** in the classic syndrome. Reviews connect SRPX2 to focal epilepsies of the rolandic/sylvian speech areas. In X-linked PMG broadly, **epilepsy is observed in ~80% of cases**. | Epilepsia 2009; IJMS review 2024 | PMID not shown in context | https://doi.org/10.1111/j.1528-1167.2009.02214.x ; https://doi.org/10.3390/ijms25074110 | (pqac-00000009, pqac-00000013) |
| Core phenotype: cortical malformation | SRPX2 is also linked to **bilateral perisylvian polymicrogyria**, a developmental malformation of the speech cortex; reviews note SRPX2 among the principal X-linked PMG genes. | BMC Genet 2007; IJMS review 2024; PMG review 2022 | PMID not shown in context | https://doi.org/10.1186/1471-2156-8-72 ; https://doi.org/10.3390/ijms25074110 ; https://doi.org/10.4103/aian.aian_97_22 | (pqac-00000010, pqac-00000013, pqac-00000015) |
| Key SRPX2 variants | Two historically emphasized **missense variants** are **p.N327S** (reported with rolandic epilepsy and verbal dyspraxia) and **p.Y72S** (reported with bilateral perisylvian polymicrogyria / rolandic seizures). The 2013 Brain study notes that the direct causal role of **p.N327S** has been questioned because of co-inheritance of another missense variant in most affected members. | Brain 2013; BMC Genet 2007 | PMID not shown in context | https://doi.org/10.1093/brain/awt161 ; https://doi.org/10.1186/1471-2156-8-72 | (pqac-00000008, pqac-00000010, pqac-00000016) |
| FOXP2 network variants (mechanistic context) | **FOXP2 p.R553H** abolishes repression/binding effects on SRPX2/uPAR regulatory sites; **FOXP2 p.M406T** causes partial loss of nuclear localization and significant loss of SRPX2 promoter repression. These FOXP2 variants are mechanistic network findings rather than primary SRPX2 disease alleles. | Hum Mol Genet 2010 | PMID not shown in context | https://doi.org/10.1093/hmg/ddq415 | (pqac-00000001, pqac-00000002, pqac-00000003) |
| Mechanism: FOXP2 represses SRPX2/uPAR | FOXP2 directly down-regulates **SRPX2** and **uPAR**; reported quantitative effects include **43.6% reduction of SRPX2 transcripts**, **38.6% reduction of uPAR transcripts**, and inhibition of **SRPX2** and **uPAR** promoter activity by about **80.2%** and **77.5%**, respectively. This supports a FOXP2→SRPX2/uPAR speech-disorder network. | Hum Mol Genet 2010 | PMID not shown in context | https://doi.org/10.1093/hmg/ddq415 | (pqac-00000003) |
| Mechanism: neuronal migration / tubulin acetylation | In utero **Srpx2 silencing** in rat cortex causes **neuronal migration defects** and later **spontaneous epileptiform activity**. **Wild-type**, but **not mutant**, human SRPX2 rescues the migration phenotype and increases **alpha-tubulin acetylation**, linking SRPX2 dysfunction to cortical development. | Brain 2013 | PMID not shown in context | https://doi.org/10.1093/brain/awt161 | (pqac-00000016) |
| Mechanism / experimental rescue | Maternal treatment with the tubulin deacetylase inhibitor **tubacin** prevented both the migration abnormalities and postnatal epileptiform consequences in the rat model, providing proof-of-principle for pathway-targeted rescue in a developmental model. This remains **preclinical**, not a human standard of care. | Brain 2013 | PMID not shown in context | https://doi.org/10.1093/brain/awt161 | (pqac-00000016, pqac-00000008) |
| Recent review perspective (2023–2024) | Recent reviews continue to place SRPX2 among important **X-linked PMG** and **X-linked epilepsy** genes. The 2024 review states SRPX2 was initially related to **Rolandic seizures, ID, speech delay, oro-facial dyspraxia, and abnormalities in brain speech areas**; the 2023 review discusses X-linked neuronal migration disorders and emphasizes limited epidemiologic data overall. | Int J Mol Sci 2024; Int J Dev Neurosci 2023 | PMID not shown in context | https://doi.org/10.3390/ijms25074110 ; https://doi.org/10.1002/jdn.10290 | (pqac-00000013, pqac-00000014) |


*Table: This table condenses the main disease names, identifiers, inheritance, phenotypes, variants, mechanisms, and key quantitative findings for the SRPX2-related speech-epilepsy-polymicrogyria spectrum. It is designed as a quick reference for integrating evidence from primary and recent review sources.*