| Domain | Best-supported finding | Quantitative data | Evidence type | Suggested ontology terms |
|---|---|---:|---|---|
| Disease definition | PRMT7-related SBIDDS is a recognizable syndromic neurodevelopmental disorder caused by biallelic PRMT7 variants; OMIM phenotype entry reported as 617157 (pqac-00000015, pqac-00000012) | 51 affected individuals from 39 families in the largest cohort (pqac-00000015) | Human clinical cohort | OMIM 617157; MONDO: not established here; disease label: PRMT7-related short stature-brachydactyly syndrome / SBIDDS |
| Synonyms | Common labels include SBIDDS and PRMT7-related disorder; expanded 2023 description emphasizes short stature, obesity, craniofacial and digital abnormalities (pqac-00000005, pqac-00000013) | N/A | Human clinical + review | SBIDDS; “PRMT7-related disorder” |
| Core neurodevelopmental phenotype | Global developmental delay / intellectual disability was universal in the 2023 cohort (pqac-00000002, pqac-00000013) | 100% GDD/ID; severity mild 27%, moderate 33%, severe 40% (pqac-00000002, pqac-00000015) | Human clinical cohort | HPO: Global developmental delay (HP:0001263); Intellectual disability (HP:0001249) |
| Seizures | Seizures are a major but non-universal feature, often treatment-responsive (pqac-00000002, pqac-00000015) | 67–70%; median onset 3 years; range 7 months–45 years; ~16% intractable (pqac-00000002, pqac-00000015) | Human clinical cohort | HPO: Seizure (HP:0001250) |
| Growth phenotype | Short stature is one of the defining manifestations (pqac-00000002, pqac-00000013) | ~80% short stature (pqac-00000002, pqac-00000013) | Human clinical cohort | HPO: Short stature (HP:0004322) |
| Digital/skeletal phenotype | Brachydactyly with metacarpal/metatarsal shortening is characteristic (pqac-00000000, pqac-00000013) | ~70% brachydactyly; delayed bone age ~50%; decreased bone density ~40% (pqac-00000000, pqac-00000002) | Human clinical cohort | HPO: Brachydactyly (HP:0001156); Delayed bone age (HP:0002750); Decreased bone mineral density (standard HPO label) |
| Hypotonia | Hypotonia is frequent early in life (pqac-00000002, pqac-00000015) | 88% (pqac-00000002) | Human clinical cohort | HPO: Hypotonia (HP:0001252) |
| Head size | Microcephaly occurs in a substantial subset, but is not universal (pqac-00000002, pqac-00000015) | ~40% (pqac-00000002) | Human clinical cohort | HPO: Microcephaly (HP:0000252) |
| Obesity/metabolic phenotype | Obesity is common and tends to emerge later, especially after puberty (pqac-00000001, pqac-00000013) | ~50–54%; delayed onset, often >10 years (pqac-00000001, pqac-00000015) | Human clinical cohort | HPO: Obesity (HP:0001513) |
| Prenatal/perinatal findings | Prenatal growth impairment is relatively common (pqac-00000000, pqac-00000012) | Intrauterine growth restriction / prenatal manifestations ~45–55%; small for gestational age ~46–50% (pqac-00000000, pqac-00000013) | Human clinical cohort | HPO: Intrauterine growth restriction (HP:0001511); Small for gestational age (HP:0001518) |
| Craniofacial phenotype | Distinctive facial gestalt supports recognition in clinic (pqac-00000000, pqac-00000013) | Frontal bossing ~70%; prognathism 72.5%; tall/prominent chin ~75% (pqac-00000000, pqac-00000012) | Human clinical cohort | HPO: Frontal bossing (HP:0002007); Prognathism (HP:0000303) |
| Ophthalmologic / auditory findings | Strabismus and hearing impairment are recurrent associated findings (pqac-00000000, pqac-00000012) | Strabismus ~45%; hearing impairment ~30% (pqac-00000000, pqac-00000012) | Human clinical cohort | HPO: Strabismus (HP:0000486); Hearing impairment (HP:0000365) |
| Neuroimaging | Brain MRI may be normal or show nonspecific abnormalities (pqac-00000000) | 13/37 MRIs unremarkable; others nonspecific (ventricular enlargement, white-matter changes) (pqac-00000000) | Human clinical cohort | HPO: Abnormal brain MRI (standard label) |
| Gene | The causal gene is PRMT7 (OMIM *610087), encoding a protein arginine methyltransferase (pqac-00000015, pqac-00000005) | Single established causal gene in current evidence base (pqac-00000008) | Human genetics + review | HGNC: PRMT7; OMIM *610087 |
| Inheritance | Disease is autosomal recessive due to biallelic PRMT7 variants (pqac-00000002, pqac-00000013) | 25 compound heterozygous, 26 homozygous; consanguinity in 44% of families (pqac-00000000, pqac-00000012) | Human clinical cohort | HP:0000007 Autosomal recessive inheritance |
| Variant spectrum | The cohort showed broad allelic heterogeneity, mostly loss-of-function classes but also missense and splice variants (pqac-00000000, pqac-00000012) | 46 variants total; 34 novel; 19 truncating (9 frameshift, 10 nonsense), 1 in-frame deletion, 9 splice, 14 missense, 3 large indels; 28 pathogenic, 3 likely pathogenic, 12 VUS (pqac-00000000, pqac-00000012) | Human clinical cohort | Sequence variant classes: nonsense, frameshift, splice-site, missense, in-frame deletion, indel |
| Diagnostic approach | Current real-world diagnosis relies on next-generation sequencing with confirmatory segregation testing and phenotype review (pqac-00000002, pqac-00000000) | Largest study: candidate variants confirmed by Sanger sequencing; dysmorphology assessment aided recognition (pqac-00000000) | Human clinical practice / cohort | NCIT: Sanger Sequencing; Whole exome/genome sequencing (standard labels); HPO-based phenotyping |
| Differential diagnosis | Differential diagnosis overlaps with other syndromic obesity / neurodevelopmental disorders (pqac-00000013) | Named comparators include Börjeson-Forssman-Lehmann, CHOPS, Chung-Jansen, Cohen, TRAPPC9-related disorders (pqac-00000013) | Human clinical interpretation | No ontology IDs asserted here |
| Mechanism: enzyme function | PRMT7 is a type III protein arginine methyltransferase that catalyzes arginine monomethylation; chromatin and non-histone substrates are implicated (pqac-00000005, pqac-00000009, pqac-00000010) | Qualitative; no disease-specific patient biomarker established (pqac-00000017) | Review + in vitro + model organism | GO: protein arginine methyltransferase activity; histone arginine methylation |
| Mechanism: neuronal | Experimental work links PRMT7 loss to altered neuronal excitability and developmental pathways, providing a plausible basis for ID/seizures, but not yet a complete human causal chain (pqac-00000005, pqac-00000008) | Qualitative | Model organism / in vitro | GO: regulation of neuron excitability; Cell Ontology: neuron |
| Mechanism: muscle/metabolism | Prmt7 deficiency in mice causes reduced skeletal muscle oxidative metabolism and age-related obesity, aligning with the human obesity/endurance phenotype (pqac-00000005, pqac-00000009) | Qualitative; mouse phenotypes include age-related obesity and reduced oxidative metabolism (pqac-00000005) | Model organism | GO: skeletal muscle tissue development; oxidative phosphorylation; adipogenesis |
| Mechanism: bone/growth | Mouse data support a role in skeletal growth and bone formation; review reports reduced body size, shortened fifth metatarsals, and reduced bone mineral content in knockout mice (pqac-00000005). A 2024 preprint links PRMT7 to PTEN-mediated osteogenesis and female-specific dwarfism in conditional knockout mice (pqac-00000006) | Qualitative; 2024 report notes dwarfism by 6 weeks in female CKO mice (pqac-00000006) | Model organism; 2024 evidence includes preprint | GO: ossification; osteoblast differentiation; Cell Ontology: osteoblast, bone marrow mesenchymal stem cell |
| Management | No disease-modifying therapy is established; care is supportive and symptom-directed, especially seizure management, developmental services, and surveillance of growth/obesity/skeletal issues (pqac-00000015, pqac-00000016) | Most seizures responsive to topiramate / sodium valproate; ~16% intractable (pqac-00000000, pqac-00000015) | Human clinical cohort | NCIT: Anticonvulsant Therapy; Physical Therapy; Occupational Therapy; Genetic Counseling |
| Current applications / implementation | Main current application is rare-disease molecular diagnosis and family counseling; syndrome recognition can improve testing yield and management planning (pqac-00000016, pqac-00000013) | 2023 cohort expanded recognizable phenotype to 51 individuals (pqac-00000012) | Clinical implementation | NCIT: Genetic Counseling; Molecular Diagnostic Testing |
| Clinical trials | No disease-specific interventional trial was identified in the available search results (tool search summary; no relevant PRMT7/SBIDDS trial returned) | 0 relevant disease-specific trials identified | Trial search / evidence gap | Not applicable |
| Unknowns / evidence gaps | Prevalence, incidence, penetrance, carrier frequency, founder variants, validated biomarkers, mortality, life expectancy, quality-of-life instruments, and gene-specific prevention strategies remain unestablished in the available literature (pqac-00000012, pqac-00000017) | Not reported in retrieved evidence | Evidence gap | Not applicable |


*Table: This table summarizes the strongest currently available evidence for PRMT7-related SBIDDS, centered on the 2023 51-person cohort and supported by mechanistic model data. It is useful for rapid knowledge-base population because it combines phenotype frequencies, inheritance and variant classes, diagnostics, management, and explicit evidence gaps in one place.*