Geleophysic dysplasia

Geleophysic dysplasia is an inherited condition that affects many parts of the body. It is characterized by abnormalities involving the bones, joints, heart, and skin.

People with geleophysic dysplasia have short stature with very short hands and feet. Most also develop thickened skin and joint deformities called contractures, both of which significantly limit mobility. Affected individuals usually have a limited range of motion in their fingers, toes, wrists, and elbows. Additionally, contractures in the legs and hips cause many affected people to walk on their toes.

The name of this condition, which comes from the Greek words for happy ("gelios") and nature ("physis"), is derived from the good-natured facial appearance seen in most affected individuals. The distinctive facial features associated with this condition include a round face with full cheeks, a small nose with upturned nostrils, a broad nasal bridge, a thin upper lip, upturned corners of the mouth, and a flat area between the upper lip and the nose (philtrum).

Geleophysic dysplasia is also characterized by heart (cardiac) problems, particularly abnormalities of the cardiac valves. These valves normally control the flow of blood through the heart. In people with geleophysic dysplasia, the cardiac valves thicken, which impedes blood flow and increases blood pressure in the heart. Other heart problems have also been reported in people with geleophysic dysplasia; these include a narrowing of the artery from the heart to the lungs (pulmonary stenosis) and a hole between the two upper chambers of the heart (atrial septal defect).

Other features of geleophysic dysplasia can include an enlarged liver (hepatomegaly) and recurrent respiratory and ear infections. In severe cases, a narrowing of the windpipe (tracheal stenosis) can cause serious breathing problems. As a result of heart and respiratory abnormalities, geleophysic dysplasia is often life-threatening in childhood. However, some affected people have lived into adulthood.

Geleophysic dysplasia is a rare disorder whose prevalence is unknown. More than 30 affected individuals have been reported.

Geleophysic dysplasia results from mutations in the ADAMTSL2 gene. This gene provides instructions for making a protein whose function is unclear. The protein is found in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells. Studies suggest that the ADAMTSL2 protein may play a role in the microfibrillar network, which is an organized clustering of thread-like filaments (called microfibrils) in the extracellular matrix. This network provides strength and flexibility to tissues throughout the body.

Mutations in the ADAMTSL2 protein likely change the protein's 3-dimensional structure. Through a process that is poorly understood, ADAMTSL2 gene mutations alter the microfibrillar network in many different tissues. Impairment of this essential network disrupts the normal functions of cells, which likely contributes to the varied signs and symptoms of geleophysic dysplasia. Researchers are working to determine how mutations in the ADAMTSL2 gene lead to short stature, heart disease, and the other features of this condition.

Genetic Testing Information

• Genetic Testing Registry: Geleophysic dysplasia 2

Genetic and Rare Diseases Information Center

• Geleophysic dysplasia

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• GELEOPHYSIC DYSPLASIA 1; GPHYSD1
• GELEOPHYSIC DYSPLASIA 2; GPHYSD2

Scientific Articles on PubMed

• PubMed

• Giray O, Kyr M, Bora E, Saylam G, Ugurlu B, Gurel D. Clinical and morphological phenotype of geleophysic dysplasia. Ann Trop Paediatr. 2008 Jun;28(2):161-4. doi: 10.1179/146532808X302206. Citation on PubMed
• Le Goff C, Morice-Picard F, Dagoneau N, Wang LW, Perrot C, Crow YJ, Bauer F, Flori E, Prost-Squarcioni C, Krakow D, Ge G, Greenspan DS, Bonnet D, Le Merrer M, Munnich A, Apte SS, Cormier-Daire V. ADAMTSL2 mutations in geleophysic dysplasia demonstrate a role for ADAMTS-like proteins in TGF-beta bioavailability regulation. Nat Genet. 2008 Sep;40(9):1119-23. doi: 10.1038/ng.199. Citation on PubMed or Free article on PubMed Central
• Marzin P, Cormier-Daire V. Geleophysic Dysplasia. 2009 Sep 22 [updated 2024 Mar 28]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK11168/ Citation on PubMed
• Pontz BF, Stoss H, Henschke F, Freisinger P, Karbowski A, Spranger J. Clinical and ultrastructural findings in three patients with geleophysic dysplasia. Am J Med Genet. 1996 May 3;63(1):50-4. doi: 10.1002/(SICI)1096-8628(19960503)63:13.0.CO;2-T. Citation on PubMed
• Rosser EM, Wilkinson AR, Hurst JA, McGaughran JM, Donnai D. Geleophysic dysplasia: a report of three affected boys--prenatal ultrasound does not detect recurrence. Am J Med Genet. 1995 Sep 11;58(3):217-21. doi: 10.1002/ajmg.1320580304. Citation on PubMed
• Santolaya JM, Groninga LC, Delgado A, Monasterio JL, Camarero C, Bilbao FJ. Patients with geleophysic dysplasia are not always geleophysic. Am J Med Genet. 1997 Oct 3;72(1):85-90. Citation on PubMed
• Scott A, Yeung S, Dickinson DF, Karbani G, Crow YJ. Natural history of cardiac involvement in geleophysic dysplasia. Am J Med Genet A. 2005 Jan 30;132A(3):320-3. doi: 10.1002/ajmg.a.30450. Citation on PubMed
• Shohat M, Gruber HE, Pagon RA, Witcoff LJ, Lachman R, Ferry D, Flaum E, Rimoin DL. Geleophysic dysplasia: a storage disorder affecting the skin, bone, liver, heart, and trachea. J Pediatr. 1990 Aug;117(2 Pt 1):227-32. doi: 10.1016/s0022-3476(05)80534-7. Citation on PubMed
• Wraith JE, Bankier A, Chow CW, Danks DM, Sardharwalla IB. Geleophysic dysplasia. Am J Med Genet. 1990 Feb;35(2):153-6. doi: 10.1002/ajmg.1320350202. Citation on PubMed