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Renpenning syndrome


Other Names:
Sutherland-Haan X-linked intellectual disability syndrome; X-linked intellectual disability with spastic diplegia; MRXS3; Sutherland-Haan X-linked intellectual disability syndrome; X-linked intellectual disability with spastic diplegia; MRXS3; MRXS8; Sutherland-Haan syndrome; X-linked intellectual disability due to PQBP1 mutations See More
Categories:
Renpenning syndrome is a genetic condition which occurs mostly in males. Signs and symptoms include the following: developmental delay, a small head (microcephaly), short stature, and distinctive facial features. Approximately two-thirds of individuals with Renpenning syndrome have moderate to severe intellectual disability. Additional features may include heart defects, muscular atrophy, cleft palate, and eye abnormalities. [1][2] Renpenning syndrome is caused by mutations in the PQBP1 gene and is inherited in an X-linked recessive manner. [1][2][3] Management involves early intervention by trained therapists along with treatment of any associated features. [2]
Last updated: 2/3/2016
The most common features of Renpenning syndrome include moderate to severe intellectual disability, microcephaly (small head size), short stature, and small testes.[4][2][3] Differences in facial features found in individuals with this condition include a long and narrow face, upslanting eye openings (palpebral fissures), a long rounded (bulbous) nose with a low-hanging separation between the nostrils, cupped ears, and short philtrum (the area between the nose and upper lip).[1] Global developmental delays are present in all individuals, with significant delays in milestones such as walking and talking.[4] Individuals with Renpenning syndrome may also experience seizures and muscle wasting (atrophy).[1] About 20% of affected individuals also have birth defects, such as a gap or split in structures that make up the eye (coloboma), a split in the roof of the mouth (cleft palate), heart malformations, and malformations of the anus.[4][2][1]  

Signs and symptoms have been found only in males; known female carriers are noted to have normal facial features, growth, development, and intelligence.[2]
Last updated: 11/28/2016

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.

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Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Cachexia
Wasting syndrome
0004326
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe
[ more ] 		0003510
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ] 		0003202
30%-79% of people have these symptoms
Abnormality of the ribs
Rib abnormalities
0000772
Alopecia
Hair loss
0001596
Decreased testicular size
Small testes
Small testis
[ more ] 		0008734
Epicanthus
Eye folds
Prominent eye folds
[ more ] 		0000286
Hypospadias 0000047
Long face
Elongation of face
Increased height of face
Increased length of face
Vertical elongation of face
Vertical enlargement of face
Vertical overgrowth of face
[ more ] 		0000276
Macrotia
Large ears
0000400
Malar flattening
Zygomatic flattening
0000272
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw
[ more ] 		0000303
Narrow face
Decreased breadth of face
Decreased width of face
[ more ] 		0000275
Prominent nose
Big nose
Disproportionately large nose
Increased nasal size
Increased size of nose
Large nose
Pronounced nose
[ more ] 		0000448
Round ear 0100830
Short philtrum 0000322
Sprengel anomaly
High shoulder blade
0000912
Thin eyebrow
Thin eyebrows
0045074
Upslanted palpebral fissure
Upward slanting of the opening between the eyelids
0000582
5%-29% of people have these symptoms
Abnormal hair laboratory examination 0003328
Abnormal thumb morphology
Abnormality of the thumb
Abnormality of the thumbs
Thumb deformity
[ more ] 		0001172
Anal atresia
Absent anus
0002023
Broad columella 0010761
Cataract
Clouding of the lens of the eye
Cloudy lens
[ more ] 		0000518
Cleft palate
Cleft roof of mouth
0000175
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Diabetes mellitus 0000819
Heterotaxy 0030853
High hypermetropia
Severe farsightedness
Severe long-sightedness
[ more ] 		0008499
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth
[ more ] 		0002705
Iris coloboma
Cat eye
0000612
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Macrodontia
Increased width of tooth
0001572
Microphthalmia
Abnormally small eyeball
0000568
Narrow mouth
Small mouth
0000160
Pectus excavatum
Funnel chest
0000767
Renal hypoplasia
Small kidneys
Underdeveloped kidneys
[ more ] 		0000089
Seizure 0001250
Sensorineural hearing impairment 0000407
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ] 		0000486
Percent of people who have these symptoms is not available through HPO
Abnormal hair morphology
Abnormality of the hair
Hair abnormality
[ more ] 		0001595
Abnormality of the rib cage 0001547
Ankylosis 0031013
Anxiety
Excessive, persistent worry and fear
0000739
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ] 		0001631
Blindness 0000618
Brachycephaly
Short and broad skull
0000248
Bulbous nose 0000414
Camptodactyly
Permanent flexion of the finger or toe
0012385
Cerebral atrophy
Degeneration of cerebrum
0002059
Coloboma
Notched pupil
0000589
Cupped ear
Cup-shaped ears
Simple, cup-shaped ears
[ more ] 		0000378
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
High palate
Elevated palate
Increased palatal height
[ more ] 		0000218
Hypermetropia
Farsightedness
Long-sightedness
[ more ] 		0000540
Hyperreflexia
Increased reflexes
0001347
Joint contracture of the hand 0009473
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Narrow foot
Slender feet
0001786
Nasal speech
Nasal voice
0001611
Pes cavus
High-arched foot
0001761
Phimosis 0001741
Poor suck
Poor sucking
0002033
Protruding ear
Prominent ear
Prominent ears
[ more ] 		0000411
Scoliosis 0002650
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Situs inversus totalis
All organs on wrong side of body
0001696
Sparse hair 0008070
Sparse lateral eyebrow
Limited hair on end of eyebrow
0005338
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Tetralogy of Fallot 0001636
Thin upper lip vermilion
Thin upper lip
0000219
Triangular face
Face with broad temples and narrow chin
Triangular facial shape
[ more ] 		0000325
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ] 		0000431
X-linked recessive inheritance 0001419
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Last updated: 7/1/2020
Renpenning syndrome is caused by mutations in the polyglutamine-binding protein 1 gene (PQBP1).[1][2][3]
Last updated: 2/3/2016
Renpenning syndrome is inherited in an X-linked recessive manner.[1][2][3] A condition is considered X-linked if the gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must generally be present in both copies of the gene to cause the disorder.[2][3]

Last updated: 2/3/2016

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
There is currently no cure for Renpenning syndrome. Management may include early educational intervention and treatment of any associated symptoms such as heart defects or eye abnormalities.[2]
Last updated: 2/3/2016
In most cases, life expectancy does not appear to be shortened for those with Renpenning syndrome.[2] 
Last updated: 2/3/2016

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

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Fragile X syndrome is a differential diagnosis but microcephaly is not a feature. Other causes of microcephaly such as fetal CMV infection, fetal alcohol syndrome, maternal phenylketonuria, autosomal recessive microcephalies and Smith-Lemli-Opitz syndrome (see this term) should be considered.
Visit the Orphanet disease page for more information.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Providing General Support

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.

Where to Start

  • You can obtain information on this topic from the Centers for Disease Control and Prevention (CDC). The CDC is recognized as the lead federal agency for developing and applying disease prevention and control, environmental health, and health promotion and education activities designed to improve the health of the people of the United States.
  • Genetics Home Reference (GHR) contains information on Renpenning syndrome. This website is maintained by the National Library of Medicine.
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.

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 Renpenning syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • My adult son has Renpenning syndrome. My daughter, who is healthy, gave birth to a son three years ago with the same. We recently learned that this condition is genetic. I would like to learn more about this condition. Are speech delays common in Renpenning syndrome? Do individuals with this condition require less sleep than average? Could my family, which has French Canadian heritage, be related to the Canadian family described by Renpenning in the 1960s? What can we expect? See answer


  1. Renpenning syndrome. Genetics Home Reference. June, 2012; http://ghr.nlm.nih.gov/condition/renpenning-syndrome.
  2. Des Portes, Vincent. Renpenning syndrome. Orphanet. June 2012; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=3242.
  3. McKusick, VA. Renpenning Syndrome 1. In: Kniffin, CL. Online Mendelian Inheritance in Man (OMIM). 9/13/2016; http://www.omim.org/entry/309500.
  4. Stevenson RE, Bennett CW, Abidi F, Kleefstra T, Porteous M, Simensen RJ, Lubs HA, Hamel BC, Schwartz CE. Renpenning syndrome comes into focus. Am J Med Genet A. 2005; 134(4):415-421. http://www.ncbi.nlm.nih.gov/pubmed/15782410.