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URL of this page: https://medlineplus.gov/genetics/condition/jansen-de-vries-syndrome/

Jansen-de Vries syndrome

Description

Jansen-de Vries syndrome is a developmental disorder that affects many parts of the body. Features of this condition include unique facial features, intellectual disability, certain personality characteristics, behavioral changes, and gastrointestinal problems. 

The signs and symptoms of Jansen-de Vries syndrome typically begin soon after birth. Affected infants often have low muscle tone (hypotonia) and feeding difficulties. Children with this disorder are often slow to develop speech and language skills, They may also be slow to acquire motor skills, such as standing or walking. People with Jansen-de Vries syndrome also tend to have intellectual disability, which can range from mild to severe.  

Additional features seen in people with Jansen-de Vries syndrome may include short stature, small hands and feet, and differences in facial features. The facial features that are common in people with this condition include a broad forehead, thin upper lip, low-set ears that are rotated backwards, and downturned corners of the mouth. 

Gastrointestinal problems, such as constipation, are also common in people with Jansen-de Vries syndrome. Many affected individuals experience recurrent episodes of nausea and vomiting (cyclic vomiting).

Though people with Jansen-de Vries syndrome tend to be very social with outgoing and friendly personalities, affected individuals may experience behavioral differences, such as anxiety disorders and attention-deficit hyperactivity disorder. Some people with Jansen-de Vries syndrome have autism-spectrum disorder, a developmental disorder that affects communication and social skills.

Other signs and symptoms of Jansen-de Vries syndrome include vision problems, an increased sensitivity to sound (hyperacusis), and a higher-than-normal pain threshold. Less commonly, people with Jansen-de Vries syndrome can have congenital heart defects. These may include openings in the wall (septum) that separates the upper or lower chambers of the heart (atrial or ventricular septal defects).

Frequency

Jansen-de Vries is a rare condition; fewer than 100 cases have been reported in the medical literature.

Causes

Certain variants (sometimes called mutations) in the PPM1D gene cause Jansen-de Vries syndrome. The PPM1D gene provides instructions for making an enzyme called protein phosphatase 1D. This enzyme is present in many of the body's tissues, including the developing brain. 

Protein phosphatase 1D belongs to a group of enzymes called the PP2C phosphatases, which regulate cell development in response to environmental stress. In particular, protein phosphatase 1D helps return the cell to its normal state after the cell's DNA has been damaged by environmental agents such as toxic chemicals or radiation. 

In addition, protein phosphatase 1D is thought to play a role in regulating areas of tightly packed DNA called heterochromatin. Because gene expression is lower when DNA is tightly packed than when DNA is loosely packed, protein phosphatase 1D helps to turn off (silence) regions of DNA that are not needed.

The variants in the PPM1D gene that cause Jansen-de Vries syndrome typically disrupt the gene's instructions, resulting in an enzyme that does not function as it should. Researchers believe that this enzyme is not able to reach the cell's nucleus. Without enough functional protein phosphatase 1D, gene expression may be altered and cells are not able to fully recover from DNA damage. Researchers are trying to learn exactly how these gene variants affect the developing brain and other body systems to cause the signs and symptoms of Jansen-de Vries syndrome. 

Inheritance

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases of this condition result from new (de novo) variants in the gene that occur during the formation of reproductive cells (eggs or sperm) in an affected individual's parent or during early embryonic development. These affected individuals typically have no history of the disorder in their family.

Other Names for This Condition

  • IDDGIP
  • Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold
  • JDVS

Additional Information & Resources

Patient Support and Advocacy Resources

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

  • Jansen S, Geuer S, Pfundt R, Brough R, Ghongane P, Herkert JC, Marco EJ, Willemsen MH, Kleefstra T, Hannibal M, Shieh JT, Lynch SA, Flinter F, FitzPatrick DR, Gardham A, Bernhard B, Ragge N, Newbury-Ecob R, Bernier R, Kvarnung M, Magnusson EA, Wessels MW, van Slegtenhorst MA, Monaghan KG, de Vries P, Veltman JA; Deciphering Developmental Disorders Study; Lord CJ, Vissers LE, de Vries BB. De Novo Truncating Mutations in the Last and Penultimate Exons of PPM1D Cause an Intellectual Disability Syndrome. Am J Hum Genet. 2017 Apr 6;100(4):650-658. doi: 10.1016/j.ajhg.2017.02.005. Epub 2017 Mar 23. Citation on PubMed
  • Kuroda Y, Murakami H, Yokoi T, Kumaki T, Enomoto Y, Tsurusaki Y, Kurosawa K. Two unrelated girls with intellectual disability associated with a truncating mutation in the PPM1D penultimate exon. Brain Dev. 2019 Jun;41(6):538-541. doi: 10.1016/j.braindev.2019.02.007. Epub 2019 Feb 20. Citation on PubMed
  • Lu X, Nannenga B, Donehower LA. PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev. 2005 May 15;19(10):1162-74. doi: 10.1101/gad.1291305. Epub 2005 May 3. Citation on PubMed
  • Porrmann J, Rump A, Hackmann K, Di Donato N, Kahlert AK, Wagner J, Jahn A, Eger I, Flury M, Schrock E, Tzschach A, Gieldon L. Novel truncating PPM1D mutation in a patient with intellectual disability. Eur J Med Genet. 2019 Jan;62(1):70-72. doi: 10.1016/j.ejmg.2018.05.006. Epub 2018 May 11. Citation on PubMed
  • Tuiskula A, Rahikkala E, Kero A, Haanpaa MK, Avela K. Jansen de Vries syndrome: Report of four new patients and review of the literature. Eur J Med Genet. 2023 Aug;66(8):104807. doi: 10.1016/j.ejmg.2023.104807. Epub 2023 Jun 28. Citation on PubMed
  • Wojcik MH, Srivastava S, Agrawal PB, Balci TB, Callewaert B, Calvo PL, Carli D, Caudle M, Colaiacovo S, Cross L, Demetriou K, Drazba K, Dutra-Clarke M, Edwards M, Genetti CA, Grange DK, Hickey SE, Isidor B, Kury S, Lachman HM, Lavillaureix A, Lyons MJ, Marcelis C, Marco EJ, Martinez-Agosto JA, Nowak C, Pizzol A, Planes M, Prijoles EJ, Riberi E, Rush ET, Russell BE, Sachdev R, Schmalz B, Shears D, Stevenson DA, Wilson K, Jansen S, de Vries BBA, Curry CJ. Jansen-de Vries syndrome: Expansion of the PPM1D clinical and phenotypic spectrum in 34 families. Am J Med Genet A. 2023 Jul;191(7):1900-1910. doi: 10.1002/ajmg.a.63226. Epub 2023 May 14. Citation on PubMed

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