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

Renpenning syndrome

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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?

The following information may help to address your question:


What is Renpenning syndrome?

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

What are the signs and symptoms of Renpenning syndrome?

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

Is speech delay or absence a common feature of Renpenning syndrome?

Speech delay is a common finding in individuals with Renpenning syndrome. In fact, it is not uncommon for individuals with this condition to delay first speech until ages 3 or 4 years. In some cases, speech may never develop. In these cases, it is not unusual for the individuals to understand simple conversations.[5] Studies have also shown that some individuals with Renpenning syndrome have speech dyspraxia or developmental dyspraxia. These conditions may  make it difficult for individuals with Renpenning syndrome to learn to speak or portray their thoughts into words.[6][7][8]
Last updated: 11/28/2016

My son did not sleep until he was three years old. My grandson is three and still requires very little sleep. Is there any association between sleep and Renpenning syndrome?

Sleeping difficulties have been described in individuals with Renpenning syndrome. While this symptom was not present in all cases reported in the medical literature, one study of multiple cases of Renpenning syndrome noted sleeping difficulties in 10 out of 13 individuals. Per the authors of this article, the difficulties became apparent in early childhood and resolved after school age.[9]
Last updated: 11/28/2016

What causes Renpenning syndrome?

Renpenning syndrome is caused by mutations in the polyglutamine-binding protein 1 gene (PQBP1).[1][2][3]
Last updated: 2/3/2016

How is Renpenning syndrome inherited?

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

How might Renpenning syndrome be treated?

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

What is the prognosis for individuals with Renpenning syndrome?

In most cases, life expectancy does not appear to be shortened for those with Renpenning syndrome.[2] 
Last updated: 2/3/2016

My family has some French Canadian heritage. Could the Renpenning syndrome in our family be traced back to the original family with Renpenning syndrome?

Although the first family described with Renpenning syndrome was from Canada, this condition is believed to be present in all racial and ethnic groups.[3] The Information Center cannot comment on your family's possible connection to the Canadian family described in the medical literature. However, if you wish to pursue this, a genetics professional may be able to assist you.
Last updated: 11/28/2016

How can I find a genetics professional in my area?

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 Genetics Home Reference.
Last updated: 11/30/2017

We hope this information is helpful. We strongly recommend you discuss this information with your doctor. If you still have questions, please contact us.

Warm regards,
GARD Information Specialist

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  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.
  5. Stevenson RE, Arena JF, Ouzts E, Gibson A, Shokeir MH, Vnencak-Jones C, Lubs HA, May M, Schwartz CE. Renpenning syndrome maps to Xp11.. Am J Hum Genet. May 1998; 62(5):1092-1101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1377092/.
  6. McLaughlin JF, Kriegsmann E. Developmental dyspraxia in a family with X-linked mental retardation (Renpenning syndrome). Dev Med Child Neurol. 1980; 22(1):84-92. http://www.ncbi.nlm.nih.gov/pubmed/7188916.
  7. Apraxia of Speech. National Institute on Deafness and Other Communication Disorders (NIDCD). June 7, 2010; https://www.nidcd.nih.gov/health/apraxia-speech. Accessed 11/28/2016.
  8. NINDS Developmental Dyspraxia Information Page. National Institute of Neurological Disorders and Stroke (NINDS). September 16, 2011; http://www.ninds.nih.gov/disorders/dyspraxia/dyspraxia.htm. Accessed 11/28/2016.
  9. D Germanaud et al. The Renpenning syndrome spectrum: new clinical insights supported by 13 new PQBP1-mutated males. Clinical Genetics. Mar 2011; 79(3):225-235. https://www.ncbi.nlm.nih.gov/pubmed/20950397.