Renpenning syndrome

Title

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:

Congenital and Genetic Diseases

Summary Summary

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

Symptoms Symptoms

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 Small head circumference Reduced head circumference Decreased size of skull Decreased circumference of cranium [ 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 testis Small testes [ 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	Increased projection of lower jaw Big lower jaw Prominent lower jaw Prominent chin Large lower jaw Increased size of lower jaw [ more ]	0000303
Narrow face	Decreased width of face Decreased breadth 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	Squint eyes Squint Cross-eyed [ more ]	0000486
1%-4% of people have these symptoms
Blindness		0000618
Brachycephaly	Short and broad skull	0000248
Brittle hair		0002299
Bulbous nose		0000414
Coloboma	Notched pupil	0000589
Cupped ear	Cup-shaped ears Simple, cup-shaped ears [ more ]	0000378
Death in childhood		0003819
Global developmental delay		0001263
Hearing impairment	Deafness Hearing defect [ more ]	0000365
High palate	Elevated palate Increased palatal height [ more ]	0000218
Low hanging columella		0009765
Short stature	Decreased body height Small stature [ more ]	0004322
Situs inversus totalis	All organs on wrong side of body	0001696
Spasticity	Involuntary muscle stiffness, contraction, or spasm	0001257
Telecanthus	Corners of eye widely separated	0000506
Percent of people who have these symptoms is not available through HPO
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
Camptodactyly	Permanent flexion of the finger or toe	0012385
Cerebral atrophy	Degeneration of cerebrum	0002059
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
Sparse hair		0008070
Sparse lateral eyebrow	Limited hair on end of eyebrow	0005338
Synostosis of the proximal phalanx of the thumb with the 1st metacarpal	Fusion of the innermost bone of the thumb with the 1st long bone of hand	0009640
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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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Do you have updated information on this disease? We want to hear from you.

Cause Cause

Renpenning syndrome is caused by mutations in the polyglutamine-binding protein 1 gene (PQBP1).^[1]^[2]^[3]

Last updated: 2/3/2016

Inheritance Inheritance

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

Diagnosis Diagnosis

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.

Treatment Treatment

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

Prognosis Prognosis

In most cases, life expectancy does not appear to be shortened for those with Renpenning syndrome.^[2]

Last updated: 2/3/2016

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Related Diseases Related Diseases

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.

Organizations Organizations

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

American Association on Intellectual and Developmental Disabilities
501 3rd Street NW
Suite 200
Washington, DC 20001
Toll-free: (800) 424-3688
Telephone: (202) 387-1968
Fax: (202) 387-2193
Website: http://www.aaidd.org
The Society for Developmental and Behavioral Pediatrics
6728 Old McLean Village Drive
McLean, VA 22101
Telephone: 703-556-9222
E-mail: info@sdbp.org
Website: http://www.sdbp.org/index.cfm

Do you know of an organization? We want to hear from you.

Learn More Learn More

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.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
Genetics Home Reference (GHR) contains information on Renpenning syndrome. This website is maintained by the National Library of Medicine.

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.

GARD Answers GARD Answers

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

Have a question? Contact a GARD Information Specialist.

References References

Renpenning syndrome. Genetics Home Reference. June, 2012; http://ghr.nlm.nih.gov/condition/renpenning-syndrome.
Des Portes, Vincent. Renpenning syndrome. Orphanet. June 2012; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=3242.
McKusick, VA. Renpenning Syndrome 1. In: Kniffin, CL. Online Mendelian Inheritance in Man (OMIM). 9/13/2016; http://www.omim.org/entry/309500.
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.