| Phenotype | Suggested HPO term(s) | Onset/course | Frequency/evidence |
|---|---|---|---|
| Macrocephaly / macrocrania | HP:0000256 Macrocephaly | Usually postnatal overgrowth; non-progressive overgrowth pattern recognized from infancy/childhood | 29/38 (76%) in 42-patient cohort; GeneReviews notes postnatal macrocephaly common (pqac-00000008, pqac-00000036, pqac-00000001) |
| Intellectual disability | HP:0001249 Intellectual disability | Developmental onset; cognition appears relatively stable, with no clear evidence of decline over time | Moderate-severe ID in 33/39 (85%); mild 16%, moderate-severe 84% in cohort summaries (pqac-00000008, pqac-00000061, pqac-00000064) |
| Developmental delay / psychomotor delay | HP:0001263 Global developmental delay; HP:0011344 Severe global developmental delay (if severe) | Early childhood onset; persistent | All 57 patients in comparative review had ID and/or psychomotor delay; GeneReviews highlights early developmental delay and expressive speech delay (pqac-00000007, pqac-00000001) |
| Expressive speech delay | HP:0002474 Expressive language delay | Early childhood; major developmental concern requiring early therapy | Frequent, but no firm cohort percentage in extracted text; specifically emphasized in GeneReviews-style management summary (pqac-00000001, pqac-00000058) |
| Autism spectrum / autistic behavior | HP:0000729 Autism | Childhood onset; behavioral severity variable | Autism in 20/33 (61%) in cohort (pqac-00000008) |
| Hypotonia | HP:0001252 Hypotonia | Typically infancy/childhood; may contribute to motor delay | 26/34 (76%) in cohort (pqac-00000008) |
| Ptosis | HP:0000508 Ptosis | Congenital/childhood, part of characteristic facial gestalt | 20/28 (71%) in cohort (pqac-00000008) |
| Deep-set eyes / characteristic facies | HP:0000490 Deeply set eye; HP:0001999 Facial asymmetry not specifically supported; HP:0000007 Autosomal dominant inheritance not phenotype | Present from childhood; recognizable facial pattern becomes more evident with age | Frequent descriptive feature in recent case reports and GeneReviews summary; no exact percentage in extracted cohort text (pqac-00000003, pqac-00000001) |
| Downslanting palpebral fissures | HP:0000494 Downslanted palpebral fissures | Childhood; part of craniofacial pattern | Common descriptive feature; no exact percentage in extracted text (pqac-00000003, pqac-00000001) |
| Sensorineural hearing loss | HP:0000407 Sensorineural hearing impairment | Often prelingual; may become more evident over time; enriched in missense-variant cases | Hearing loss common: 21/27 children and 12/13 adults in GeneReviews summary; significantly more frequent with missense variants vs deletions/truncating variants (pqac-00000013, pqac-00000049, pqac-00000057) |
| Calcification/ossification of external ears | HP:0008608 Calcification of pinna; HP:0011397 Abnormal external ear cartilage (broader fallback) | Typically develops in later childhood/adolescence; one of the hallmark progressive signs | 14/28 (50%) overall and 12/12 (100%) adults in cohort; cardinal features usually emerge between 10-16 years (pqac-00000008, pqac-00000035) |
| Distal muscle wasting / distal amyotrophy | HP:0003699 Amyotrophy; HP:0008947 Distal amyotrophy | Usually first noticed around age 11; progressive with age | Progressive; clear age-related increase in cohort, first noticed around age 11 (pqac-00000034, pqac-00000065) |
| Joint contractures | HP:0001371 Flexion contracture; HP:0002829 Arthrogryposis multiplex congenita not supported | Typically begins around age 10; progressive | Appears in later childhood/adolescence; worsens with age (pqac-00000034, pqac-00000065) |
| Ataxia / gait difficulty | HP:0001251 Ataxia; HP:0001288 Gait disturbance | Rare; may be progressive in some individuals | Reported in subset only; GeneReviews notes progressive musculoskeletal impairment can lead to walking difficulty and eventual wheelchair dependence (pqac-00000010, pqac-00000063) |
| Seizures | HP:0001250 Seizure | Variable onset; monitor clinically for new seizures | 6/29 (21%) in cohort (pqac-00000008) |
| Corpus callosum anomaly / dysgenesis | HP:0001273 Agenesis of corpus callosum; HP:0006989 Dysgenesis of corpus callosum | Congenital/early neuroimaging finding | More frequent in missense SNV group; ~20% reported in recent review/case synthesis (pqac-00000049, pqac-00000023, pqac-00000006) |
| Cataract | HP:0000518 Cataract | Often later-onset; may become apparent in puberty/adulthood | Adult-enriched feature; included among age-related manifestations in cohort and reviews (pqac-00000035, pqac-00000036, pqac-00000055) |
| Disturbed glucose metabolism / diabetes mellitus | HP:0003074 Hyperglycemia; HP:0000819 Diabetes mellitus | Usually later childhood/adulthood; progressive metabolic monitoring recommended | Considered a cardinal biochemical feature; adults may require oral hypoglycemics and/or insulin (pqac-00000036, pqac-00000055, pqac-00000059) |
| Elevated alpha-fetoprotein | HP:0005914 Increased circulating alpha-fetoprotein level | Can be elevated from infancy and may persist without clear age-related trend in some individuals | 9/18 (50%) overall in cohort; 4/11 and 5/7 in subgroups (pqac-00000031, pqac-00000034) |
| Anemia | HP:0001903 Anemia | Variable; part of biochemical phenotype, may warrant repeated monitoring | 5/21 (24%) overall in cohort (pqac-00000034, pqac-00000035) |
| Sparse body hair | HP:0008070 Sparse body hair | More recognizable with age/adulthood | Described as characteristic adult feature; no exact percentage in extracted text (pqac-00000035, pqac-00000055) |
| Cryptorchidism | HP:0000028 Cryptorchidism | Congenital/childhood in affected males | About half of affected males in GeneReviews summary (pqac-00000003, pqac-00000055) |
| Hypothyroidism | HP:0000821 Hypothyroidism | Congenital or childhood-onset in subset; endocrine surveillance recommended | Rare overall but enriched in missense-variant group in comparative study; several cases reported in recent review (pqac-00000049, pqac-00000022, pqac-00000055) |
| Behavioral dysregulation / aggression / self-injury | HP:0000708 Behavioral abnormality; HP:0000734 Stereotypy; HP:0000742 Self-injurious behavior | Childhood to adolescence; variable severity | Common behavioral phenotype in GeneReviews; severe case showed response to sertraline in 2024 report (pqac-00000001, pqac-00000060) |


*Table: This table maps major Primrose syndrome manifestations to suggested HPO terms with onset/progression notes and frequency data where available, mainly from the 42-patient cohort and GeneReviews-style summary. It is useful for disease knowledge base curation and phenotype annotation.*