| Domain | Specific feature (plain language) | Suggested HPO term(s) | Frequency/statistic (with denominator) | Typical onset/temporal notes | Key source/citation context IDs |
|---|---|---|---|---|---|
| Cohort overview | Longitudinal follow-up in dedicated natural-history cohorts | HP:0000007 Autosomal dominant inheritance; HP:0003674 Progressive | MGH: 47 patients; 81% had at least 1 follow-up; among those followed ≥5 years, progression observed in all. French: 12 molecularly confirmed patients, median follow-up 7 years | Progressive multisystem disease across childhood to adulthood | (pqac-00000017, pqac-00000021, pqac-00000016) |
| Growth | Intrauterine growth restriction / prenatal growth deficiency | HP:0001511 Intrauterine growth retardation | French: 12/12 (100%) | Prenatal onset; postnatal short stature persists | (pqac-00000018) |
| Growth | Postnatal growth failure / short stature | HP:0004322 Short stature; HP:0001510 Growth delay | French: postnatal height median about -3.5 SD; MGH: short stature described as common, but no cohort-wide % in retrieved text | Begins in infancy/childhood and persists | (pqac-00000018, pqac-00000017) |
| Hearing | Hearing impairment | HP:0000365 Hearing impairment | French: 7/12 (58%) | Detectable from about age 2 years; mixed conductive/sensorineural etiologies | (pqac-00000016) |
| Hearing / genotype-phenotype | p.Arg496Cys associated with less hearing loss | HP:0000365 Hearing impairment | Qualitative reduction vs other variant groups in MGH cohort | Suggests milder sensory involvement for this variant subgroup | (pqac-00000021) |
| Vision | Visual problems (mainly refractive error/strabismus) | HP:0000505 Visual impairment; HP:0000486 Strabismus; HP:0000545 Myopia/Hyperopia as applicable | French: 9/12 (75%) | Childhood onset | (pqac-00000016) |
| Craniofacial | Prognathism | HP:0000303 Mandibular prognathia | French: 11/12 (92%) | Childhood, persistent | (pqac-00000018) |
| Craniofacial | Maxillary hypoplasia | HP:0000327 Hypoplasia of the maxilla | French: 9/11 (82%) | Childhood | (pqac-00000018) |
| Craniofacial | Narrow/short palpebral fissures | HP:0000581 Narrow palpebral fissure | French: 9/12 (75%) | Childhood | (pqac-00000018) |
| Craniofacial | Prominent chin | HP:0000303 Mandibular prognathia | MGH: 35/47 (74%), severe in 7/35 | Persistent dysmorphic feature | (pqac-00000020) |
| Neurodevelopment | Neurodevelopmental disorders in early childhood | HP:0012758 Neurodevelopmental abnormality | French: 80% in preschool age | Preschool onset | (pqac-00000018) |
| Neurodevelopment | Developmental delay / intellectual disability | HP:0001263 Global developmental delay; HP:0001249 Intellectual disability | French: developmental delay/intellectual disability 9/12 (75%); MGH: intellectual disability in 32% | Early childhood onset; persistent | (pqac-00000019, pqac-00000020) |
| Neurobehavioral | Autism spectrum disorder / social communication difficulties | HP:0000729 Autism; HP:0000733 Stereotypy/behavioral abnormality | MGH: ASD diagnosis in 72%; social challenges in 91%; academic accommodations in 44/47 (94%) | Usually recognized in childhood; major QoL/education impact | (pqac-00000020) |
| Neurobehavioral | ADHD | HP:0007018 Attention deficit hyperactivity disorder | MGH: 14 patients (56% of subgroup discussed) had combined inattentive/hyperactive ADHD | Childhood; may be undertreated | (pqac-00000036) |
| Neurologic / cerebrovascular | Brain MRI abnormalities | HP:0410263 Abnormal brain MRI; HP:0002500 Abnormal cerebral white matter morphology | French: 5/8 imaged | Childhood/adolescence | (pqac-00000019) |
| Neurologic / vascular | Moyamoya-associated recurrent strokes | HP:0002527 Stroke; HP:0002134 Moyamoya disease | French: 1 patient | First reported from age 26 years in cohort | (pqac-00000018, pqac-00000019) |
| Skin | Thickened / stiff skin | HP:0008067 Thickened skin; HP:0000974 Skin sclerosis | French: 8/12 (67%); MGH: described as common/progressive but no overall % in retrieved text | Typically emerges in school age / around age 6; progressive | (pqac-00000016, pqac-00000019, pqac-00000038) |
| Musculoskeletal | Muscular hypertrophy / pseudomuscular build | HP:0009041 Muscular hypertrophy | French: 9/12 (75%) | Appears from about age 6 years | (pqac-00000018) |
| Musculoskeletal | Joint limitation / contractures | HP:0001371 Flexion contracture; HP:0001382 Joint limitation | French: 8/9 (89%); MGH: severe contractures 5/47 (11%), less severe contractures 23/47 (49%) | Median onset 6 years in French cohort; earliest contracture at 26 months in MGH; progressive from small joints to generalized limitation | (pqac-00000016, pqac-00000020) |
| Musculoskeletal | Stiff gait | HP:0002361 Stiff gait | MGH: 44/47 (94%) | Progressive mobility impact | (pqac-00000020) |
| Musculoskeletal | Brachydactyly | HP:0001156 Brachydactyly | French: 11/11 (100%); MGH: 30/47 (64%) | Early childhood / first years of life | (pqac-00000016, pqac-00000020) |
| Musculoskeletal | Small hands | HP:0200055 Small hand | French: 8/8 (100%) | Early childhood | (pqac-00000016) |
| Musculoskeletal | Clinodactyly | HP:0030084 Clinodactyly | French: 4/8 (50%); MGH: 33/47 (70%) | Early childhood | (pqac-00000016, pqac-00000020) |
| Musculoskeletal | Toe 2-3 syndactyly | HP:0001770 Syndactyly of toes | MGH: 31/47 (66%) | Congenital/early childhood | (pqac-00000020) |
| Musculoskeletal | Scoliosis | HP:0002650 Scoliosis | MGH: 10/47 (21%) | Childhood/adolescence | (pqac-00000020) |
| Musculoskeletal | Fractures | HP:0002757 Pathologic fracture / recurrent fractures | MGH: 13/47 (28%) | From infancy to adulthood; authors note apparently elevated fracture burden | (pqac-00000020, pqac-00000036) |
| Skeletal imaging | Thickened calvarium | HP:0002684 Thick calvarium | French: 5/7 (71%) | Childhood | (pqac-00000016) |
| Skeletal imaging | Enlarged vertebral pedicles | HP:0008467 Abnormal vertebral pedicle morphology | French: 7/10 (70%) | Childhood | (pqac-00000016) |
| Cardiovascular | Congenital heart defects | HP:0001627 Abnormality of the cardiovascular system; HP:0001626 Congenital cardiovascular malformation | French: 7/12 (58%) | Often identified in infancy/childhood | (pqac-00000016) |
| Cardiovascular | Pulmonary hypertension / pulmonary arterial hypertension | HP:0002092 Pulmonary hypertension | French: 5/8 assessed (63%) | Early childhood in Shone complex; early adolescence in others; major life-threatening complication | (pqac-00000016) |
| Cardiovascular | Aortic hypoplasia | HP:0004970 Ascending aorta hypoplasia / aortic hypoplasia | MGH: overall % not retrieved; p.Ile500Thr subgroup 3/5 (60%) had moderate/severe aortic hypoplasia | Childhood recognition; important surveillance lesion | (pqac-00000017, pqac-00000021) |
| Cardiovascular / genotype-phenotype | p.Arg496Cys associated with less growth restriction and less aortic hypoplasia | HP:0001511 Intrauterine growth retardation; HP:0004970 Aortic hypoplasia | Qualitative reduction vs other variants in MGH cohort | Suggests variant-specific attenuation of some core phenotypes | (pqac-00000017, pqac-00000021) |
| Respiratory / airway | Multilevel laryngotracheal stenosis | HP:0001609 Laryngotracheal stenosis | French: 2 cases specifically described; MGH: severe feature recognized, % not retrieved in quoted text | Progressive; may emerge in childhood/adolescence; potentially lethal | (pqac-00000019, pqac-00000037) |
| Respiratory | Obstructive sleep apnea | HP:0010535 Sleep apnea | French: 4 patients | Childhood/adolescence | (pqac-00000019) |
| Respiratory / pleural | Pleural effusion | HP:0002202 Pleural effusion | French: 6/10 (60%) | Often later/progressive; contributed to chronic respiratory failure in severe cases | (pqac-00000019) |
| Respiratory | Chronic respiratory failure | HP:0002878 Respiratory insufficiency | French: 2 adolescents | Severe late complication | (pqac-00000019) |
| ENT / sinus-mastoid imaging | Opacified mastoids / sinusitis / opacified sinuses | HP:0010628 Abnormal mastoid morphology; HP:0000246 Sinusitis | MGH: 30%, 38%, and 13% respectively | Chronic/recurrent ENT burden | (pqac-00000037) |
| Endocrine / puberty | Precocious puberty (reported mainly in females) | HP:0000826 Precocious puberty | French: 8 females affected; MGH notes underascertainment due to age distribution | Around age 8 years in French cohort | (pqac-00000019, pqac-00000038) |
| Immune | Hypogammaglobulinemia | HP:0004313 Decreased circulating immunoglobulin level | French: 4 patients; MGH outside testing: 7/13 (54%) had hypogammaglobulinemia | Variable; may prompt vaccine-response testing or IgG replacement in selected cases | (pqac-00000019, pqac-00000020) |
| Gastrointestinal | Abdominal pain | HP:0002027 Abdominal pain | MGH: 40% | Chronic symptom; multifactorial | (pqac-00000027) |
| Gastrointestinal | Celiac disease | HP:0002608 Celiac disease | MGH review incidence 6% vs ~1% general population | Screening may be considered | (pqac-00000038) |
| Mortality / prognosis | Disease-related deaths | HP:0001423 Sudden death / mortality not directly mapped | MGH: 2 deaths; French: 3 deaths | Causes included complex cardiovascular disease, airway stenosis, PAH crisis, mesenteric ischemia, severe esophageal atresia | (pqac-00000017, pqac-00000018) |


*Table: This table summarizes cohort-derived phenotype frequencies, timing, and genotype-phenotype observations for Myhre syndrome from the major recent natural-history studies. It is useful for building disease knowledge-base phenotype assertions with suggested HPO mappings and citation-ready evidence links.*