GENOTYPE × PHENOTYPE × TIME
The 61-person corpus connects five molecular-context categories plus one unresolved roster group, fifteen clinical lanes, age and sex context, and within-person change. Missing information remains missing; genotype is an analytic frame, not a prediction of outcome.
SCIENTIFIC SUMMARY
The evidence is strongest at gene level, increasingly specific in experimental cell and tissue systems, and still incomplete for many human multisystem features.
ESTABLISHED
Heterozygous ASH1L loss of function is an established cause of autosomal-dominant neurodevelopmental disorder. Developmental, language, intellectual, behavioral, motor, sleep, and seizure phenotypes are supported across human series. Missense, in-frame, splice, CNV, and complex findings still require finding-specific interpretation.
COHORT OBSERVATION
The records extend into oral-motor and dental function, GI and fuel state, ENT and airway, movement and pain, immune and barrier findings, connective and skeletal features, cardiac/autonomic physiology, puberty, medication and anesthesia response, and adult support needs. Uneven assessment prevents prevalence claims.
LONGITUDINAL SIGNAL
Eight evidence-mapped histories span seven forms of regression, loss of access, or severe deterioration. The cohort also contains continued acquisition, explicit no-regression histories, and complete recovery after severe illness. Each trajectory requires its own chronology and differential.
TESTABLE HYPOTHESIS
Direct experiments show that ASH1L effects depend on cell identity and state. The human records motivate—but do not prove—a cross-scale hypothesis about persistent or incompletely resolving clinical states after physiological load. “Failure to terminate” is therefore a defined experimental question, not a cohort diagnosis.
THE ANALYTIC FRAME
Every person remains linked to molecular class, exact allele when confirmed, sex, current age, relatedness, co-findings, source depth, and chronology. That structure makes recurrence, co-occurrence, and data gaps visible while preventing a thin record from becoming a false negative or a molecular class from becoming a prognosis.
15 female · 17 male
31 have a sequence-positioned protein consequence; one remains outside protein-position math.6 female · 12 male
Allele-specific interpretation is required; missense is not assumed equivalent to haploinsufficiency.2 female · 3 male
Retained as a multigene molecular context, separate from sequence-only comparisons.1 female · 2 male
Multiple molecular or inheritance factors remain visible rather than being forced into a cleaner class.0 female · 2 male
The protein consequence is not sufficiently resolved for position-based analysis.0 female · 1 male
Visible in the full roster but excluded from class-specific inference.RECURRENCE & MULTI-VARIANT STRUCTURE
The map separates an opposite-sex same-stop frameshift pair, a same-sex truncating pair, an internal-to-physician LoF match, five related missense cases, one dual-missense individual, and one truncating-plus-missense individual.
Review the molecular structures →PUBLIC POSITIONAL RECURRENCE · RESIDUE 1222
Duplicated public source rows remain provenance rather than independent people. Connected-cohort and clinician-shared records stay in broad protein segments and are not asserted here as exact residue-level matches.
Examine residue 1222 →Exact allele, class, relatedness, and co-findings define the valid descriptive set.
Positive, negative, unresolved, and unreported states remain distinct.
Baseline, change, measurement, intervention, and recovery define the trajectory.
WHERE COVERAGE PARTITIONS ARE COMPLETE
Seizure/EEG and cardiac/autonomic pages show mutually exclusive sex-by-molecular-class source-coverage partitions. They describe what is mapped, unresolved, negative, or unreported—not prevalence or a genotype effect. Sleep examples carry molecular class and chronology. Other lanes retain molecular context in the analytic record, but this public site does not invent genotype frequencies from incomplete reporting.
SEVEN CLINICAL CHAPTERS
The grouping makes the material readable without pretending the systems are isolated. Sleep can alter seizures and access; oral mechanics connect to nutrition and airway; immune, barrier, autonomic, and medication effects can change several lanes at once.
Milestones, language, learning, retention, retrieval, reliable access, regression, school, and adult function.
42 people mapped · 9 formal evidence anchorsOpen chapter →Event types, EEG background, sleep, unresolved spells, captured nonepileptic events, triggers, and recovery.
35 people mapped · 13 formal evidence anchorsOpen chapter →Tone, coordination, feet, laterality, pain, weakness, tics, stereotypies, event capture, loss, rehabilitation, and recovery.
39 people mapped · 7 formal evidence anchorsOpen chapter →Feeding mechanics, chewing, swallowing, dentition, bowel and fuel state, hearing, airway, growth, bone, and connective features.
Four linked systems · sex-specific source coverageOpen chapter →Infection, antibody response, inflammatory assays, ENT overlap, skin and oral barriers, bruising, healing, and endothelial signals.
25 people mapped · 6 formal evidence anchorsOpen chapter →Rhythm, ECG, syncope-like events, orthostatic physiology, breathing, temperature, sweating, urinary findings, and event testing.
23 people mapped · 6 formal evidence anchorsOpen chapter →Diagnoses and assessments, aggression, anxiety, rigidity, self-injury, sensory regulation, psychiatric mimics, intervention response, and adult change.
36 people mapped · 4 formal evidence anchorsOpen chapter →LONGITUDINAL PHENOTYPE
The same chronology standard is applied to development, seizures, sleep, movement, oral–GI function, immune and barrier events, cardiac/autonomic physiology, medication, procedures, and adult function.
Follow the age-ordered trajectoriesWHAT IS VISIBLE ACROSS AGES
This is current-age composition—not age of onset or a cross-sectional prevalence comparison. The complete age-by-system source map and the deep within-person stories live together on the longitudinal page.
1infant <1
8toddler 1–3
20child 4–11
13adolescent 12–17
17adult 18+
1passed / deceased
1age not reported
Feeding, tone, development, sleep, GI function, ENT/airway, growth, and neurologic events can all precede a settled diagnostic narrative.
Oral, GI, immune, bone, hormonal, and autonomic documentation remains uneven. Missing follow-up must stay visible as missing.
Communication, memory access, epilepsy, sleep, movement, GI, immune, cardiac/autonomic, bone, mental-health, and support needs remain part of adult natural history.
FIFTEEN-LANE COVERAGE
Each person is assigned once: positive only; positive plus an explicit negative or unresolved candidate; negative only; unresolved with no positive; or unreported. Formal-record status is evidence strength within those groups—not another person count.
State definitions: “Positive + negative / unresolved” means that the same person has positive content plus either an explicit-negative subfeature or an unresolved candidate within that broad lane. “Unresolved, no positive” includes a candidate with or without an explicit-negative subfeature, but no positive content. These are person-level display states; they are not severity grades.
Formal evidence is nested within the mapped group, not added as another person count: L01 2 · L02 21 · L03 9 · L04 13 · L05 7 · L06 4 · L07 3 · L08 5 · L09 7 · L10 4 · L11 6 · L12 6 · L13 7 · L14 6 · L15 2.
Formal record, parent-reported formal content, parent observation, visual candidate, administrative permission, and inference remain distinct labels.
CLINICAL USE
Define the person’s own baseline, preserve timing and recovery, then distinguish neurologic, sleep, pain, gastrointestinal, immune, endocrine, cardiac, autonomic, medication, and environmental explanations.