| Domain | Feature/Statistic | Value | Study/Population | Notes |
|---|---|---:|---|---|
| Clinical features | Developmental delay and/or intellectual disability | 97% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000009) | Core neurodevelopmental feature in the largest cohort |
| Clinical features | Failure to thrive | 67.7% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000009) | Common early growth problem |
| Clinical features | Feeding difficulties | 66.3% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000009) | Tube feeds reported in 25.5% in extended cohort summary (pqac-00000010) |
| Clinical features | Constipation | 63.8% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000009) | Frequent gastrointestinal comorbidity |
| Clinical features | Short stature | 57.8% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000009) | Postnatal growth deficiency is a hallmark finding |
| Clinical features | Hypertrichosis cubiti | 57.0% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000009) | Historically considered highly suggestive, but not universal |
| Clinical features | Vertebral anomalies | 46.9% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000009) | Supports skeletal surveillance |
| Clinical features | Hypotonia | 72.4% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000011) | Later associated with LoF variants in cohort analysis |
| Clinical features | Hyperactivity | 44.3% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000011) | Behavioral/psychiatric burden is substantial |
| Clinical features | Aggressive behavior | 33.0% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000011) | Behavioral support often needed |
| Clinical features | Autism spectrum disorder | 21.3% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000011) | Not universal but clinically relevant |
| Clinical features | Seizures | 20.0% | Sheppard et al. 2021, surveyed subset of cohort (pqac-00000011) | Reported association with non-LoF variants |
| Clinical features | Structural brain abnormality on imaging | 57.5% | Sheppard et al. 2021, imaged subgroup (n=52) (pqac-00000011) | Includes corpus callosum and myelination abnormalities |
| Clinical features | Cardiac abnormalities | 35.8% | Sheppard et al. 2021, evaluated subgroup (29/81) (pqac-00000011) | Structural anomalies also emphasized in review literature |
| Clinical features | Genitourinary anomalies | 46.8% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000010) | Renal anomaly 28.6%; uterine/testicular anomalies 16.9% |
| Clinical features | Recurrent infections | 25.7% | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000010) | Supports consideration of immune evaluation |
| Clinical features | Abnormal immunoglobulins | 53.8% | Sheppard et al. 2021, tested subgroup (n=13) (pqac-00000010) | Small tested subset only |
| Developmental milestones | Sitting independently | Median 10 months (range 6-36) | Sheppard et al. 2021, multicenter cohort (pqac-00000010) | Delayed relative to typical development |
| Developmental milestones | Standing independently | Median 17 months (range 8-60) | Sheppard et al. 2021, multicenter cohort (pqac-00000010) | Marked gross motor delay |
| Developmental milestones | Walking independently | Median 20 months (range 11-60) | Sheppard et al. 2021, multicenter cohort (pqac-00000009, pqac-00000010) | Frequently cited milestone delay in WSS |
| Developmental milestones | First words | Median 18 months (range 8-60) | Sheppard et al. 2021, multicenter cohort (pqac-00000009, pqac-00000010) | Language delay common but variable |
| Clinical features | Short stature | 90.9% | Lin et al. 2023, Chinese cohort (n=11) (pqac-00000002, pqac-00000005) | Higher than in Sheppard cohort |
| Clinical features | Developmental delay | 90.9% | Lin et al. 2023, Chinese cohort (n=11) (pqac-00000002, pqac-00000005) | Confirms high frequency across populations |
| Clinical features | Intellectual disability | 72.7% | Lin et al. 2023, Chinese cohort (n=11) (pqac-00000002, pqac-00000005) | Smaller cohort, likely ascertainment effects |
| Clinical features | Patent ductus arteriosus | 57.1% | Lin et al. 2023, Chinese cohort imaging findings (pqac-00000002) | Frequent cardiovascular imaging finding in this cohort |
| Clinical features | Patent foramen ovale | 42.9% | Lin et al. 2023, Chinese cohort imaging findings (pqac-00000002) | Common but potentially incidental in some children |
| Clinical features | Abnormal corpus callosum | 50.0% | Lin et al. 2023, Chinese cohort imaging findings (pqac-00000002) | Supports neuroimaging when clinically indicated |
| Clinical features | Developmental delay | 84.6% | Lin et al. 2023, combined Chinese cases (n=52) (pqac-00000002) | Review-level estimate across reported Chinese patients |
| Clinical features | Intellectual disability | 84.6% | Lin et al. 2023, combined Chinese cases (n=52) (pqac-00000002) | Similar to developmental delay frequency |
| Clinical features | Short stature | 80.8% | Lin et al. 2023, combined Chinese cases (n=52) (pqac-00000002) | Suggests growth phenotype may be prominent in Chinese reports |
| Clinical features | Delayed bone age | 68.0% | Lin et al. 2023, combined Chinese cases (n=52) (pqac-00000002) | Bone age may be delayed or, in other reports, advanced |
| Variant spectrum | Distinct KMT2A variants identified | 82 | Sheppard et al. 2021, multicenter cohort (n=104) (pqac-00000009, pqac-00000012) | 69/82 were novel |
| Variant spectrum | Novel variants among distinct variants | 84% (69/82) | Sheppard et al. 2021, multicenter cohort (pqac-00000009, pqac-00000012) | Highlights allelic heterogeneity |
| Variant spectrum | De novo variants | 55.8% | Sheppard et al. 2021, cohort summary (pqac-00000011) | Likely underestimate due to incomplete parental testing |
| Variant spectrum | Frameshift variants | 37.8% | Sheppard et al. 2021, variant spectrum (pqac-00000012) | Largest variant class in this cohort |
| Variant spectrum | Nonsense variants | 29.3% | Sheppard et al. 2021, variant spectrum (pqac-00000012) | Supports haploinsufficiency mechanism |
| Variant spectrum | Missense variants | 20.7% | Sheppard et al. 2021, variant spectrum (pqac-00000012) | Missense variants often cluster in functional domains |
| Variant spectrum | Splice-site variants | 11.0% | Sheppard et al. 2021, variant spectrum (pqac-00000012) | Rounded from reported 11% |
| Variant spectrum | Variants absent from gnomAD v2.1.1 | 80/82 | Sheppard et al. 2021, variant spectrum (pqac-00000012) | Consistent with rarity and pathogenic enrichment |
| Variant spectrum | Variants identified | 11 total (3 known, 8 novel) | Lin et al. 2023, Chinese cohort (n=11) (pqac-00000002) | No hotspot variant detected |
| Variant spectrum | HGMD-listed KMT2A variants | 349 total | Lin et al. 2023 background summary (pqac-00000002) | 273 disease-causing, 76 possible disease-causing |
| Variant spectrum | Reported KMT2A variants in review | 322 | Yu et al. 2022 review (pqac-00000001) | Included missense, nonsense, frameshift, and splicing variants |
| Variant spectrum | Variants in exons 3 and 27 | >50% of pathogenic variants | Yu et al. 2022 review (pqac-00000001) | Review-level observation, not cohort-specific |
| Treatment/management | rhGH-treated patients with satisfactory height gain | 2/2 | Lin et al. 2023, Chinese cohort (pqac-00000002) | One patient developed accelerated bone age |
| Treatment/management | Growth hormone deficiency | 18.8% | Sheppard et al. 2021, endocrine subgroup (pqac-00000010) | Supports endocrine assessment in selected patients |
| Treatment/management | Growth hormone deficiency | 18.8%-50% | Yu et al. 2022 review (pqac-00000001) | Range reflects literature variability |
| Epidemiology | Estimated prevalence | <1/1,000,000 | Lin et al. 2023 background summary (pqac-00000005) | Authors also noted <400 reported cases worldwide at that time |
| Epidemiology | Revised prevalence estimate | ~1 in 25,000-40,000 | Yu et al. 2022 review (pqac-00000008) | Review noted ascertainment likely increased with sequencing |


*Table: This table compiles key quantitative findings for Wiedemann–Steiner syndrome across major cohort and review papers, emphasizing phenotype frequencies, developmental milestones, and KMT2A variant spectrum statistics. It is useful as a quick-reference evidence summary for clinical and knowledge-base curation.*