| entity/interval | principal dosage-sensitive genes | characteristic phenotype | inheritance/sex effects | strongest evidence |
|---|---|---|---|---|
| Broad partial Xq duplication (heterogeneous larger duplications across Xq, e.g., Xq23-q26.3) | Interval-dependent; reported neurodevelopmental genes in one 20 Mb Xq23-q26.3 case included **ARHGEF6, PHF6, HPRT1, SLC9A6** | Variable but commonly developmental delay/intellectual disability, short stature, microcephaly, and multiple congenital findings; a 2023 adult female with de novo inverted tandem Xq23-q26.3 duplication had **extremely short stature** and **mild mental deficiency** | Not a single syndrome; phenotype depends on duplicated segment and X-inactivation. Females may be unaffected or variably affected with **skewed/non-random X-inactivation**; males are often more severely affected (pqac-00000013) | 2023 case report delineating de novo inverted tandem Xq23-q26.3 duplication in an adult female; review-style statements that partial Xq duplications are associated with ID/short stature and female phenotype depends on X-inactivation (pqac-00000013) |
| **Xq25 STAG2 duplication cohesinopathy** | **STAG2** is the shortest-region-of-overlap and principal driver; neighboring duplicated genes can include **XIAP, THOC2, GRIA3, SH2D1A** | Intellectual disability (often mild-moderate), behavioral problems, seizures in about one-third, autism in a minority, characteristic facial features; more severe disease with **triplication** | Mainly affects males; female carriers show variable outcomes from normal to borderline or mild ID, with clinically important effects linked to **skewed X-inactivation** | 2015 cohort of **28 affected males** (15 familial, 13 singleton) identified through ~27,000 males tested for neurodevelopmental delay; duplicated intervals **202-746 kb**; behavioral problems **68%**, seizures **32%**, short stature **21%** (pqac-00000000, pqac-00000001, pqac-00000002) |
| **MECP2 duplication syndrome, Xq28 (MRXSL)** | **MECP2** is the major disease-contributing gene; nearby genes may modify severity, especially **RAB39B**, and sometimes **IRAK1, L1CAM, GDI1** | Core phenotype: infantile hypotonia, severe developmental delay/intellectual disability, poor/absent speech, progressive spasticity, recurrent respiratory infections, epilepsy, GI problems, autistic features, dysmorphism; severity worsens with **triplication** and more complex structures | X-linked disorder affecting primarily males; estimated prevalence about **1/100,000 live male births** in one 2024 paper and **1/150,000 males** in a 2022 review. Female carriers often milder due to X-inactivation, but affected females occur. In the 2024 cohort, terminal duplications had more **de novo** events than tandem duplications | 2024 deep-genomic cohort of **137 individuals**: duplication sizes **64.6 kb-16.5 Mb**; structural classes were tandem **48%**, terminal **22%**, inverted triplication **20%**, other complex rearrangements **10%**; genotype-phenotype analyses showed worsening of survival and neurologic severity from tandem to triplication, with MECP2 RNA-protein correlation (pqac-00000013, pqac-00000011). Clinical synthesis review in 2022 summarizes 20 years of phenotype and prevalence (pqac-00000017, pqac-00000015, pqac-00000016) |
| Distal **Xq28 duplications excluding MECP2** (including K/L-mediated and int22h1/int22h2-mediated regions) | Does **not** include **MECP2**; likely multigenic distal Xq28 dosage effects rather than a single confirmed driver | Can resemble MECP2 duplication syndrome: regressive intellectual disability, progressive neurologic disorder/spasticity, epilepsy, recurrent infections, and brain MRI abnormalities | Sex/inheritance effects not established as clearly as classic MECP2 duplication syndrome; evidence is currently based on small case numbers/case reports | 2023 case report of a **17-year-old boy** with a **1.2 Mb distal Xq28 duplication** spanning both K/L-mediated and int22h1/int22h2-mediated regions: epilepsy from age 6, progressive lower-extremity spasticity requiring surgery at 14, recurrent infection, and hypoplasia of corpus callosum/cerebellum/brain stem; authors concluded that **MECP2 alone may not explain all symptoms** of distal Xq28 duplication (pqac-00000019) |


*Table: This table summarizes the main clinically relevant Xq duplication entities discussed in the evidence gathered so far. It distinguishes the broad heterogeneous category from better-defined subtypes such as Xq25/STAG2 and Xq28/MECP2 duplications, which is useful for disease-scope clarification and genotype-phenotype interpretation.*