| Entity | Molecular lesion | Typical sex / inheritance | Defining phenotype / course | Evidence strength | Key caveat |
|---|---|---|---|---|---|
| AUTSX3 / autism susceptibility, X-linked 3 (OMIM 300496) | Historical MECP2-associated susceptibility label; not well delineated as a modern, discrete clinical entity in the gathered evidence | X-linked; historically associated with males carrying MECP2 variants, but current literature tends to subsume such cases under broader MECP2-related disorders (pqac-00000001, pqac-00000006) | Autism/autistic features may occur with MECP2 variants, but the gathered evidence does not define a consistent standalone natural history, phenotype spectrum, prevalence, or diagnostic criteria for AUTSX3 specifically (pqac-00000001, pqac-00000002) | Sparse / historical | Do **not** transfer Rett syndrome prevalence, survival, or treatment data directly to AUTSX3; current evidence supports treating AUTSX3 as a legacy nosologic label within the wider MECP2-related disorder spectrum (pqac-00000001, pqac-00000002) |
| Rett syndrome due to MECP2 loss of function | MECP2 loss-of-function variants; >300 LOF variants documented, with 8 hotspot variants accounting for >60% of cases (pqac-00000008, pqac-00000009) | Predominantly females; X-linked dominant with major effect in heterozygous females; males usually require mosaicism or 47,XXY to present with classic RTT (pqac-00000003, pqac-00000008, pqac-00000009) | Regression after early apparently typical development with loss of spoken language and purposeful hand use, hand stereotypies, gait impairment; chronic neurodevelopmental course with stabilization after regression and multisystem comorbidity burden (pqac-00000009, pqac-00000011, pqac-00000013) | Strong | RTT statistics apply to RTT, not to historical AUTSX3; X-inactivation modifies severity and blood XCI may not reflect brain disease (pqac-00000008, pqac-00000014) |
| Severe neonatal encephalopathy in males (OMIM 300673) | Usually severe pathogenic MECP2 loss-of-function variants, often overlapping with classic female RTT-causing variants in hemizygous males (pqac-00000000, pqac-00000006) | Typically 46,XY males; X-linked; often de novo | Severe early encephalopathy with neonatal/infantile onset, profound developmental impairment, ventilatory needs, and early death; considered among the most severe male MECP2 phenotypes (pqac-00000000, pqac-00000005, pqac-00000006) | Moderate | Male MECP2 genotype-phenotype prediction remains limited; severity is broad and individual cases may not fit neatly into categories (pqac-00000003, pqac-00000007) |
| X-linked intellectual developmental disorder 13 / PPM-X (OMIM 300055) | Pathogenic MECP2 variants, including missense, truncating, and other alleles associated with non-classic male phenotypes (pqac-00000001, pqac-00000002, pqac-00000006) | Usually males; X-linked | Cognitive impairment / intellectual disability with variable neurologic and behavioral involvement; may be static or less progressive than RTT/neonatal encephalopathy and may include autism-related features (pqac-00000000, pqac-00000002, pqac-00000006) | Moderate | Boundaries with AUTSX3 and other historical MECP2 male diagnoses are blurred in modern literature; classification has shifted toward broader “MECP2-related disorders in males” (pqac-00000000, pqac-00000001) |
| MECP2 duplication syndrome (OMIM 300260) | Copy-number gain / duplication (or triplication) involving MECP2; dosage gain rather than loss of function (pqac-00000004) | Predominantly males; X-linked, often inherited from asymptomatic or mildly affected carrier mothers with skewed XCI (pqac-00000004, pqac-00000005) | Hypotonia, developmental delay, moderate-to-severe intellectual disability, poor/absent speech, autistic features, progressive spasticity, recurrent respiratory infections, GI problems, epilepsy in >50%, and possible motor regression/loss of ambulation over time (pqac-00000004) | Strong | Pathobiology is opposite in direction to RTT (gene dosage gain vs loss); should not be grouped with AUTSX3/RTT for prognosis or treatment assumptions (pqac-00000004, pqac-00000005) |


*Table: This table distinguishes the historical AUTSX3 label from better-supported MECP2-related entities. It is useful for preventing misclassification, especially the inappropriate reuse of Rett syndrome statistics for AUTSX3.*