VUS COMPARATOR
Pulatov 2025 is shown separately.
The single case is useful descriptive context, but the ASH1L missense finding remained a VUS and additional variants were present. It is not included in confirmed-variant totals.
PHENOTYPE OVERVIEW
Choose the clinical chapter that matches the question.
Use this page to find the clinical chapter that matches the question; it is not a prognosis or symptom checklist.
7 CLINICAL CHAPTERS
Each chapter starts with one main clinical question.
The clinical areas overlap in real life, but each chapter starts from a different question. Open the primary chapter first, then follow the linked system when the observation crosses domains.
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Development & memory
Primary question: Was a skill acquired, retained, retrieved, expressed, variably accessible, or truly lost?
Language, learning, memory domains, processing, communication access, school, adaptive function, and adult change.
Development / language · Function / school / adult · Behavior / sensoryOpen chapter →Neurology & seizures
Primary question: What event was observed, what physiology was captured, and what remains unresolved?
Seizures, EEG background, spells, sleep-state context, event recovery, and cardiorespiratory overlap.
Seizure / EEG / spells · Sleep / state / fatigueOpen chapter →Movement, gait & tics
Primary question: Is the movement long-standing, episodic, limited by pain, or newly acquired?
Tone, strength, gait, coordination, laterality, pain, movement events, vision, mobility, and recovery.
Motor / tone / gait / visionOpen chapter →Oral, GI, ENT & growth
Primary question: Which area—oral function, GI, ENT or airway, growth, endocrine, or bone—best matches the concern?
Oral motor function, swallowing, dentition, GI motility, nutrition and hydration, hearing and airway, growth, endocrine, and bone.
Oral / dental / chewing · GI / fuel / bowel · ENT / hearing / airway · Growth / endocrine / puberty / boneOpen chapter →Immune, skin & mucosa
Primary question: What was measured, what was observed, and what only happened around the same time?
Infection, antibody response, inflammation, mucosa, skin, healing, allergy, vascular and barrier observations, and recovery.
Immune / skin / mucosalOpen chapter →Cardiac & autonomic
Primary question: Which measurements taken during the event can distinguish heart rhythm, fainting, breathing, hydration, temperature, urinary, or neurologic causes?
Heart rate and rhythm, orthostatic symptoms, faint-like events, oxygenation, sweating, temperature, urinary findings, and recovery.
Autonomic / cardiac / urinary / temperatureOpen chapter →Neurobehavioral & mental health
Primary question: What is the observable change, and which body, brain, communication, mental-health, or environmental state could produce it?
Regulation, distress, attention, anxiety, rigidity, mood, sensory processing, participation, diagnosis, and support response.
Behavior / sensory · Function / school / adultOpen chapter →WHERE TO STARTStart where the measurement can answer the presenting concern.A linked chapter is a second reading path—not proof that the two systems share one mechanism.
Scroll horizontally to review every column.
| Presenting concern | Primary chapter | Important linked chapter | First measurement rule |
|---|---|---|---|
| A new staring, collapse, confusion, or nocturnal event | Neurology & seizures | Cardiac & autonomic | Capture the representative event and recovery; align EEG, ECG, oxygenation, sleep, and position with the clinical question. |
| A skill is inconsistent or appears lost | Development & memory | Neurology & seizures | Anchor the prior baseline and compare the same function across state, support, and recovery. |
| Feeding, bowel, hearing, airway, or growth burden | Oral, GI, ENT & growth | Immune, skin & mucosa | Keep oral, GI, ENT, growth, mucosal, and nutritional measurements parallel rather than forcing one pathway. |
| Gait, weakness, pain, laterality, or episodic movement | Movement, gait & tics | Neurology & seizures | Separate persistent motor capacity from episodic access, pain, orthopedic burden, and captured events. |
| Illness-linked or prolonged multisystem change | Immune, skin & mucosa | Natural history & state transitions | Record objective findings, competing explanations, intervention, and the return-to-baseline curve. |
| Behavior, withdrawal, aggression, fear, or participation change | Neurobehavioral & mental health | Development & memory | Describe the observation first; assess safety, communication, pain, physiology, mental health, environment, and support. |
CROSS-STUDY HUMAN PHENOTYPE MATRIXEach study keeps its own participant count.Each result is shown with the participant count used by that study. Results from different or overlapping studies are not combined.
HUMAN STUDY SOURCES106 rare-variant reports or cohorts, 1 VUS case, 2 Tourette-susceptibility studies, and 1 American Epilepsy Society abstract
REPORTED FEATURE RESULTS55Shown with each study’s participant count
CONNECTED PEOPLE63Shown separately as information availability and never combined with published study results
Scroll horizontally to review every column.
| Study | Study N | Intellectual disability / developmental delay | Autism spectrum disorder | Seizure or epilepsy | Dysmetria / ataxia | Feeding or GI entry | Overlap / limits |
|---|---|---|---|---|---|---|---|
| Okamoto et al. 2017Peer reviewed · case report | 1Not extracted from the primary abstract. | 1/1severe intellectual disability | NRNot reported / not extracted | NRNot reported / not extracted | NRNot reported / not extracted | NRNot reported / not extracted | This individual is repeated in later literature-synthesis tables; do not count the synthesis as a new participant. |
| Shen et al. 2019Peer reviewed · case report | 1Not extracted from the primary abstract. | NRNot reported / not extracted | NRNot reported / not extracted | NRNot reported / not extracted | NRNot reported / not extracted | NRNot reported / not extracted | The case is repeated in later literature-synthesis tables; retain the primary report as the participant source. |
| Liu et al. 2021Peer reviewed · family study | 22 female | 2/2mild intellectual disability | NRNot reported / not extracted | 2/2seizures | NRNot reported / not extracted | NRNot reported / not extracted | Two people, one family, and one independent allele event. Later literature tables repeat both individuals. |
| Cordova et al. 2024Peer reviewed · case series | 33 male | 2/3ID/DD (intellectual disability/developmental delay) | 3/3ASD (autism spectrum disorder) | 2/3Seizures | 2/3Dysmetria/ataxic gait | NRNot reported / not extracted | One Brain Gene Registry participant appears again in the Papendorp 2025 supplement. The article's prior-literature totals are a synthesis, not a new cohort. |
| Papendorp et al. 2025Preprint · mixed human/model prospective cohort | 2310 male; 13 female | 20/221 missing · mild or moderate ID, or borderline cognitive classification | 9/221 missing · ASD consensus: Y only | CONFLICTPrimary text and supplement do not reconcile | 16/23appendicular and/or truncal ataxia coded present | 17/23any feeding or gastrointestinal entry versus 'none noted' | At least one participant overlaps Cordova 2024; the later AES N=26 abstract is likely an expanded overlapping cohort. Never sum these denominators. |
| Liao et al. 2025Peer reviewed · case report | 11 female | 1/1mild intellectual disability; WAIS 65 | NRNot reported / not extracted | 0/1no seizures | NRNot reported / not extracted | NRNot reported / not extracted | The article reviews prior variants; only the new index proband is counted here. |
| Nie et al. 2025Conference abstract · prospective natural history | 2612 male; 14 female | NRNot reported / not extracted | NRNot reported / not extracted | NRNot reported / not extracted | NRNot reported / not extracted | NRNot reported / not extracted | Same research group and highly similar cohort architecture as Papendorp 2025; treat as an expanded overlapping cohort and never sum the two study Ns. |
How overlapping studies and source disagreements are handled
OVERLAPPING PARTICIPANTS
Papendorp 23 and the American Epilepsy Society 26 are not added together.
At least one Cordova participant appears again in Papendorp, and the American Epilepsy Society cohort is likely an expanded overlapping cohort. No combined participant total is calculated.
SOURCE DISAGREEMENT
The Papendorp seizure and EEG counts do not reconcile.
The primary text and public supplement report different sex-specific counts. Both are documented in the download, so no combined seizure or EEG total is calculated.
See how much connected-family information is available across all 15 areas
Scroll horizontally to review every column.
| Clinical area | Information available | Area not addressed | Of those, original source document available | Total |
|---|---|---|---|---|
| Birth / feeding | 29 | 34 | 5 | 29 + 34 = 63 |
| Genetics | 63 | 0 | 35 | 63 + 0 = 63 |
| Development / language | 50 | 13 | 12 | 50 + 13 = 63 |
| Seizure / EEG / spells | 43 | 20 | 16 | 43 + 20 = 63 |
| Sleep / state / fatigue | 41 | 22 | 7 | 41 + 22 = 63 |
| Oral / dental / chewing | 37 | 26 | 5 | 37 + 26 = 63 |
| GI / fuel / bowel | 38 | 25 | 6 | 38 + 25 = 63 |
| ENT / hearing / airway | 33 | 30 | 6 | 33 + 30 = 63 |
| Motor / tone / gait / vision | 49 | 14 | 12 | 49 + 14 = 63 |
| Behavior / sensory | 49 | 14 | 14 | 49 + 14 = 63 |
| Immune / skin / mucosal | 38 | 25 | 11 | 38 + 25 = 63 |
| Autonomic / cardiac / urinary / temperature | 30 | 33 | 10 | 30 + 33 = 63 |
| Growth / endocrine / puberty / bone | 37 | 26 | 11 | 37 + 26 = 63 |
| Medication / anesthesia | 40 | 23 | 9 | 40 + 23 = 63 |
| Function / school / adult | 34 | 29 | 3 | 34 + 29 = 63 |
HOW TO READ EVERY CHAPTER
Two rules travel with every chapter.
A chapter is not a diagnosis
Clinical domains organize questions. Ordinary differential diagnosis, additional findings, medications, environment, and unrelated disease remain active.
A new change deserves its own timeline
The person’s baseline, onset, context, measurement, intervention, duration, and recovery should remain attached.