National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Primrose syndrome


Other Names:
Intellectual disability-cataracts-calcified pinnae-myopathy syndrome; Ossified ear cartilages with mental deficiency, muscle wasting, and bony changes
Categories:
Primrose syndrome was originally described in 1982 and fewer than a dozen cases have been reported in the literature. The most distinctive clinical feature is a calcification (hardening) of the outer ear. Other findings include characteristic facial features, a large head (macrocephaly), and intellectual disability. A variety of neurological signs such as brain calcifications, autism, and behavioral abnormalities have been reported in some cases. Additional features such as diabetes, sparse body hair, and muscle wasting become apparent in adulthood. Research has found that some cases of Primrose syndrome are caused by a mutation in the ZBTB20 gene . Most cases have been sporadic.[1][2]
Last updated: 8/24/2016
Signs and symptoms of primrose syndrome vary from person to person and may include:[1][3][4]
  • Characteristic facial features (deep set eyes, small lower jaw, drooping of the eyelid) and a large head (macrocephaly)
  • Autism, behavioral abnormalities, and intellectual disability
  • Neurological symptoms including brain calcifications, partial or complete absence of the structure that connects the two hemispheres of the brain (agenesis of the corpus callosum) muscle wasting, and problems with coordination (ataxia)
  • Cataracts
  • Calcification (hardening) of the outer ear, recurrent ear infections, and hearing loss
  • Sparse body hair 
  • Torus palatinus (a hard bony growth in the roof of the mouth) 
  • Diabetes
  • Fluid filled lesions (cysts) in the bones 
Last updated: 9/8/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 72 |
Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Abnormal palate morphology
Abnormality of the palate
Abnormality of the roof of the mouth
[ more ] 		0000174
Anemia
Low number of red blood cells or hemoglobin
0001903
Bone cyst
Bone cysts
0012062
Calcification of the auricular cartilage 0005103
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Conductive hearing impairment
Conductive deafness
Conductive hearing loss
[ more ] 		0000405
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood
[ more ] 		0002376
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait
[ more ] 		0001288
Hip contracture 0003273
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypogonadism
Decreased activity of gonads
0000135
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Irregular vertebral endplates 0003301
Kyphosis
Hunched back
Round back
[ more ] 		0002808
Macrotia
Large ears
0000400
Myopathy
Muscle tissue disease
0003198
Osteolysis
Breakdown of bone
0002797
Posterior scalloping of vertebral bodies 0005121
Scoliosis 0002650
30%-79% of people have these symptoms
Anonychia
Absent nails
Aplastic nails
[ more ] 		0001798
Bilateral cryptorchidism 0008689
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Gynecomastia
Enlarged male breast
0000771
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ] 		0011800
Narrow chest
Low chest circumference
Narrow shoulders
[ more ] 		0000774
Narrow iliac wings 0002868
Pectus excavatum
Funnel chest
0000767
Plagiocephaly
Flat head syndrome
Flattening of skull
Rhomboid shaped skull
[ more ] 		0001357
Seizure 0001250
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Synophrys
Monobrow
Unibrow
[ more ] 		0000664
5%-29% of people have these symptoms
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness
[ more ] 		0000718
Autism 0000717
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Congenital hypothyroidism
Underactive thyroid gland from birth
0000851
Hypergonadotropic hypogonadism 0000815
Restlessness 0000711
Self-injurious behavior
Self-injurious behaviour
0100716
Percent of people who have these symptoms is not available through HPO
Absent axillary hair 0002221
Absent facial hair 0002550
Autosomal dominant inheritance 0000006
Basilar impression 0005758
Brachycephaly
Short and broad skull
0000248
Broad forehead
Increased width of the forehead
Wide forehead
[ more ] 		0000337
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye
[ more ] 		0000490
Diabetes mellitus 0000819
Distal amyotrophy
Distal muscle wasting
0003693
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth
[ more ] 		0002714
Dystrophic fingernails
Poor fingernail formation
0008391
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Generalized osteoporosis 0040160
Genu valgum
Knock knees
0002857
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion
[ more ] 		0000327
Increased size of the mandible 0040309
Knee flexion contracture 0006380
Macrocephaly
Increased size of skull
Large head
Large head circumference
[ more ] 		0000256
Malar flattening
Zygomatic flattening
0000272
Metatarsus adductus
Front half of foot turns inward
0001840
Narrow mouth
Small mouth
0000160
Neurodegeneration
Ongoing loss of nerve cells
0002180
Osteoporosis 0000939
Pes cavus
High-arched foot
0001761
Posterior polar cataract 0001115
Ptosis
Drooping upper eyelid
0000508
Short distal phalanx of finger
Short outermost finger bone
0009882
Sparse scalp hair
Reduced/lack of hair on scalp
Scalp hair, thinning
Sparse, thin scalp hair
sparse-absent scalp hair
[ more ] 		0002209
Sporadic
No previous family history
0003745
Superiorly displaced ears 0008541
Thick lower lip vermilion
Increased volume of lower lip
Plump lower lip
Prominent lower lip
[ more ] 		0000179
Truncal obesity 0001956
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Last updated: 7/1/2020
Primrose syndrome is thought to be caused by a mutation in the ZBTB20 gene . Most cases have been sporadic. However, affected individuals have a 50% risk for passing the mutation to each of their offspring.[1][4]
Last updated: 8/24/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Primrose syndrome. Click on the link to view a sample search on this topic.

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  1. Mattioli, Francesca, et al.. Novel de novo mutations in ZBTB20 in Primrose syndrome with congenital hypothyroidism. American Journal of Medical Genetics. June, 2016; 170(6):1626-1629. http://www.ncbi.nlm.nih.gov/pubmed/?term=27061120.
  2. Additional features of unique Primrose syndrome phenotype. American Journal of Medical Genetics. June, 2011; 155A (6):1379-1383. http://www.ncbi.nlm.nih.gov/pubmed/?term=21567911.
  3. Battisti C, Dotti MT, Cerase A, Rufa A, Sicurelli F, Scarpini C, Federico A. The Primerose syndrome with progressive neurological involvement and cerebral calcification. J Neurol. 2002;
  4. Primrose Syndrome. Online Mendelian Inheritance in Man (OMIM). August 8, 2016; http://www.omim.org/entry/259050.