| Domain | Autosomal-dominant COL12A1 disease | Autosomal-recessive/biallelic COL12A1 disease | Ontology suggestions |
|---|---|---|---|
| Onset | Usually congenital or childhood hypotonia/motor delay; adolescent presentation and symptomatic distal weakness beginning in the fourth decade also occur. (pqac-00000010, pqac-00000021) | Congenital onset; reduced fetal movement, hypotonia, hip dysplasia, and delayed milestones occurred in all eight individuals in the 2025 cohort; arthrogryposis occurred in 4/8. (pqac-00000017) | HP:0002808 Abnormal fetal movements; HP:0001252 Hypotonia; HP:0001263 Global developmental delay; HP:0002751 Kyphosis |
| Severity and course | Generally mild, with retained ambulation and slowly progressive weakness; childhood function may be relatively preserved before adult distal weakness. Rare severe neonatal respiratory presentations occur. (pqac-00000010, pqac-00000018) | Variable but usually more severe: 5/8 had profound congenital weakness, minimal milestones, respiratory insufficiency, and feeding difficulty; 3/8 had mild-to-moderate weakness and walked independently. Motor ability often improved slowly without regression. (pqac-00000016, pqac-00000017) | HP:0003701 Proximal muscle weakness; HP:0002460 Distal muscle weakness; HP:0002376 Developmental regression—typically absent |
| Motor function and weakness | Axial, proximal, or distal weakness; adult disease may selectively involve anterior lower-leg muscles, finger extensors, and intrinsic hand muscles. In a later review, 31/33 reported dominant cases remained ambulant. (pqac-00000010, pqac-00000018) | Proximal and distal lower-limb weakness ranging from isolated hip-flexor weakness to profound generalized weakness. Five of 15 literature cases never walked; some ambulant children walked at 15 months, 16 months, or 3 years. (pqac-00000017, pqac-00000018) | HP:0003324 Generalized muscle weakness; HP:0008948 Pelvic-girdle muscle weakness; HP:0009055 Distal lower-limb muscle weakness; HP:0002355 Difficulty walking |
| Joints and spine | Joint hyperlaxity in 5/6 patients in a 2019 series; pes planus common, with occasional ankle contractures. Distal hypermobility may coexist with proximal contractures; kyphoscoliosis can progress. (pqac-00000003, pqac-00000010) | Distal laxity in all eight recent patients; contractures in 6/8, often involving finger flexors and knees. Progressive scoliosis requiring surgery occurred in 3/8 and thoracic kyphoscoliosis in 2/8. (pqac-00000017) | HP:0001382 Joint hypermobility; HP:0001371 Flexion contracture; HP:0001763 Pes planus; HP:0002650 Scoliosis; HP:0002751 Kyphosis; HP:0002802 Arthrogryposis multiplex congenita |
| Skin, wound healing, and craniofacial findings | Soft/doughy skin, atrophic scarring, abnormal wound healing, and high-arched palate have been reported; reliable frequencies are unavailable. (pqac-00000002, pqac-00000003, pqac-00000004) | Dysmorphic features were universal in the recent cohort; gingival hypertrophy occurred in 6/8, with micrognathia and dental abnormalities also reported. Velvety palms/soles occurred, whereas keloid scarring was absent; skin-feature frequencies otherwise unavailable. (pqac-00000016, pqac-00000017) | HP:0000974 Hyperextensible skin; HP:0001075 Atrophic scars; HP:0000278 Retrognathia; HP:0000212 Gingival overgrowth; HP:0000164 Abnormality of the dentition; HP:0000218 High-arched palate |
| Respiratory, feeding, and cardiac involvement | No cardiac or pulmonary disease was detected in the six-patient 2019 series; reported FVC values in later compiled cases ranged approximately 58–115% predicted. Rare severe dominant neonatal respiratory failure is reported. Feeding frequencies unavailable. (pqac-00000010, pqac-00000018, pqac-00000021) | Seven of eight required nasogastric or gastrostomy feeding. Respiratory involvement ranged from absent to ventilator dependence from birth; cardiac findings occurred in 4/8. Exact lesion-specific frequencies are unavailable. (pqac-00000017) | HP:0002093 Respiratory insufficiency; HP:0002020 Gastroesophageal reflux; HP:0008872 Feeding difficulties in infancy; HP:0011968 Feeding by nasogastric tube; HP:0011471 Gastrostomy tube feeding; HP:0001627 Abnormal heart morphology |
| Laboratory and electrophysiology | CK is usually normal or mildly elevated, although compiled values ranged from about 42–1,310 U/L. One congenital case had normal CK, EMG, and nerve-conduction studies. (pqac-00000003, pqac-00000021) | CK was normal in four and mildly elevated in two reported patients. EMG/nerve-conduction evidence was unavailable in the extracted cohort. (pqac-00000017) | HP:0003236 Elevated serum creatine kinase; HP:0003458 EMG abnormality—variable/not established |
| Biopsy and imaging | Muscle biopsy may show mild, nonspecific, non-dystrophic myopathy with fiber-size variation and increased connective tissue. Imaging can demonstrate rectus-femoris, posterior-thigh, neck, and lumbar muscle involvement. (pqac-00000003, pqac-00000018, pqac-00000022) | Four biopsies showed mild myopathic changes without dystrophic necrosis/regeneration. MRI ranged from normal to severe diffuse atrophy and fatty replacement; posterior-thigh and rectus-femoris involvement may be selective. (pqac-00000016, pqac-00000020) | HP:0003199 Decreased muscle mass; HP:0003712 Abnormal muscle fiber morphology; HP:0003808 Abnormal muscle biopsy finding; UBERON:0001383 skeletal muscle tissue |
| Molecular mechanism | Glycine substitutions and in-frame exon-skipping variants affecting the triple-helical region typically exert dominant-negative effects, causing intracellular retention, impaired secretion, or abnormal fibril-associated collagen-XII deposition. Mutant-allele siRNA restored ECM localization in exon-52-deletion fibroblasts. (pqac-00000003, pqac-00000010, pqac-00000017) | Usually biallelic loss of function, producing markedly reduced or absent collagen XII. Fibroblast collagen-XII abundance correlated with clinical severity in the eight-patient cohort. (pqac-00000011, pqac-00000019) | GO:0030198 extracellular matrix organization; GO:0030199 collagen fibril organization; GO:0005201 extracellular matrix structural constituent; GO:0062023 collagen-containing extracellular matrix; CL:0000057 fibroblast |
| Prognosis and function | Most patients retain ambulation; weakness may remain mild for years but can progress in adulthood. No genotype-specific survival, mortality, or validated quality-of-life statistics are available. (pqac-00000010, pqac-00000018) | Lifelong congenital disease with severity ranging from ventilator-dependent profound disability to independent walking. Improvement without motor regression is documented, but survival rates, life expectancy, and validated quality-of-life outcomes are unavailable. (pqac-00000016, pqac-00000017) | HP:0002355 Difficulty walking; HP:0003547 Shoulder-girdle muscle weakness; ICF mobility and self-care domains |


*Table: Evidence-based comparison of autosomal-dominant and biallelic COL12A1-related myopathic Ehlers-Danlos syndrome across clinical, diagnostic, molecular, and prognostic domains. Frequencies are reported only where available, and evidence gaps are explicitly marked.*