Liebenberg syndrome

Liebenberg syndrome is a condition that is characterized by abnormal development of the elbows, wrists, and hands. Joint deformities (contractures) that limit the movement of the elbows, wrists, and hands are common. The signs and symptoms and the severity of Liebenberg syndrome can vary among affected individuals.

In people with Liebenberg syndrome, the bones and tissues of the elbows typically resemble those of the knees, and the arm bones near the elbow are shaped more like related structures in the leg. These changes limit the range of motion in the elbows.

Individuals with Liebenberg syndrome may have bones in the wrists that are joined together (fused), resembling related structures in the ankles and heels. This fusion can cause the hand to bend permanently toward the thumb (radial deviation).

Abnormalities of the hands and fingers may also be seen in individuals with Liebenberg syndrome. The bones in the hand that connect the wrist to the fingers (metacarpals) tend to be longer than normal, resembling the bones in the foot that connect the ankle to the toes. People with Liebenberg syndrome typically have fingers that are short (brachydactyly). Some affected individuals have a little finger that is permanently bent (camptodactyly) or fingers that are fused together (syndactyly).

Individuals with Liebenberg syndrome typically have no other signs and symptoms that are related to this condition. The development of the legs and feet is not affected.

Liebenberg syndrome is rare. Fewer than 1 in 1 million people are estimated to have this condition.

Liebenberg syndrome is caused by changes in a region of the long (q) arm of chromosome 5 near the PITX1 gene. The PITX1 gene provides instructions for making a protein that plays a critical role in the development of the legs and feet by regulating the activity of other genes involved in their development.

The changes on chromosome 5 that cause Liebenberg syndrome involve the deletion, insertion, or rearrangement of genetic material near the PITX1 gene. These changes affect regions of DNA known as regulatory elements that help turn genes on or off during development.

The chromosome changes that are associated with Liebenberg syndrome cause the PITX1 gene to become abnormally active when the arms and hands are developing. Because the PITX1 protein normally directs the development of the legs and feet, the bones and tissues in the arms and hands develop more like those in the legs and feet. 

Genetic Testing Information

• Genetic Testing Registry: Brachydactyly-elbow wrist dysplasia syndrome

Genetic and Rare Diseases Information Center

• Brachydactyly-elbow wrist dysplasia syndrome

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• LIEBENBERG SYNDROME; LBNBG

Scientific Articles on PubMed

• PubMed

• Al-Qattan MM, Al-Thunayan A, Alabdulkareem I, Al Balwi M. Liebenberg syndrome is caused by a deletion upstream to the PITX1 gene resulting in transformation of the upper limbs to reflect lower limb characteristics. Gene. 2013 Jul 15;524(1):65-71. doi: 10.1016/j.gene.2013.03.120. Epub 2013 Apr 12. Citation on PubMed
• Bompadre O, Rouco R, Darbellay F, Rauseo A, Guerard-Millet F, Gentile C, Kmita M, Andrey G. Liebenberg syndrome severity arises from variations in Pitx1 locus topology and proportion of ectopically transcribing cells. Nat Commun. 2025 Jul 9;16(1):6321. doi: 10.1038/s41467-025-61615-2. Citation on PubMed
• DeLaurier A, Schweitzer R, Logan M. Pitx1 determines the morphology of muscle, tendon, and bones of the hindlimb. Dev Biol. 2006 Nov 1;299(1):22-34. doi: 10.1016/j.ydbio.2006.06.055. Epub 2006 Jul 14. Citation on PubMed
• Duboc V, Logan MP. Pitx1 is necessary for normal initiation of hindlimb outgrowth through regulation of Tbx4 expression and shapes hindlimb morphologies via targeted growth control. Development. 2011 Dec;138(24):5301-9. doi: 10.1242/dev.074153. Epub 2011 Nov 9. Citation on PubMed or Free article on PubMed Central
• Kragesteen BK, Brancati F, Digilio MC, Mundlos S, Spielmann M. H2AFY promoter deletion causes PITX1 endoactivation and Liebenberg syndrome. J Med Genet. 2019 Apr;56(4):246-251. doi: 10.1136/jmedgenet-2018-105793. Epub 2019 Feb 2. Citation on PubMed
• Mennen U, Mundlos S, Spielmann M. The Liebenberg syndrome: in depth analysis of the original family. J Hand Surg Eur Vol. 2014 Nov;39(9):919-25. doi: 10.1177/1753193413502162. Epub 2013 Aug 12. Citation on PubMed
• Seoighe DM, Gadancheva V, Regan R, McDaid J, Brenner C, Ennis S, Betts DR, Eadie PA, Lynch SA. A chromosomal 5q31.1 gain involving PITX1 causes Liebenberg syndrome. Am J Med Genet A. 2014 Nov;164A(11):2958-60. doi: 10.1002/ajmg.a.36712. Epub 2014 Aug 14. No abstract available. Citation on PubMed
• Spielmann M, Brancati F, Krawitz PM, Robinson PN, Ibrahim DM, Franke M, Hecht J, Lohan S, Dathe K, Nardone AM, Ferrari P, Landi A, Wittler L, Timmermann B, Chan D, Mennen U, Klopocki E, Mundlos S. Homeotic arm-to-leg transformation associated with genomic rearrangements at the PITX1 locus. Am J Hum Genet. 2012 Oct 5;91(4):629-35. doi: 10.1016/j.ajhg.2012.08.014. Epub 2012 Sep 27. Citation on PubMed or Free article on PubMed Central