U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Geleophysic dysplasia 2(GPHYSD2)

MedGen UID:
481684
Concept ID:
C3280054
Disease or Syndrome
Synonym: GPHYSD2
 
Gene (location): FBN1 (15q21.1)
 
Monarch Initiative: MONDO:0013612
OMIM®: 614185

Disease characteristics

Excerpted from the GeneReview: Geleophysic Dysplasia
Geleophysic dysplasia, a progressive condition resembling a lysosomal storage disorder, is characterized by short stature, short hands and feet, progressive joint limitation and contractures, distinctive facial features, progressive cardiac valvular disease, and thickened skin. Intellect is normal. The characteristic clinical findings are likely to be present in the first year of life. Cardiac, airway, and pulmonary involvement result in death before age five years in approximately 33% of individuals. [from GeneReviews]
Authors:
Pauline Marzin  |  Valérie Cormier-Daire   view full author information

Additional description

From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/geleophysic-dysplasia

Clinical features

From HPO
Short palm
MedGen UID:
334684
Concept ID:
C1843108
Finding
Short palm.
Short foot
MedGen UID:
376415
Concept ID:
C1848673
Finding
A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).
Aortic valve stenosis
MedGen UID:
1621
Concept ID:
C0003507
Pathologic Function
The presence of a stenosis (narrowing) of the aortic valve.
Mitral regurgitation
MedGen UID:
7670
Concept ID:
C0026266
Disease or Syndrome
An abnormality of the mitral valve characterized by insufficiency or incompetence of the mitral valve resulting in retrograde leaking of blood through the mitral valve upon ventricular contraction.
Mitral valve prolapse
MedGen UID:
7671
Concept ID:
C0026267
Disease or Syndrome
One or both of the leaflets (cusps) of the mitral valve bulges back into the left atrium upon contraction of the left ventricle.
Mitral stenosis
MedGen UID:
44466
Concept ID:
C0026269
Disease or Syndrome
An abnormal narrowing of the orifice of the mitral valve.
Tricuspid stenosis
MedGen UID:
21678
Concept ID:
C0040963
Disease or Syndrome
A narrowing of the orifice of the tricuspid valve of the heart.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Tip-toe gait
MedGen UID:
98104
Concept ID:
C0427144
Finding
An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait.
Joint stiffness
MedGen UID:
56403
Concept ID:
C0162298
Sign or Symptom
Joint stiffness is a perceived sensation of tightness in a joint or joints when attempting to move them after a period of inactivity. Joint stiffness typically subsides over time.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Ovoid vertebral bodies
MedGen UID:
344549
Concept ID:
C1855665
Finding
When viewed in lateral radiographs, vertebral bodies have a roughly rectangular configuration. This term applies if the vertebral body appears rounded or oval.
Limitation of joint mobility
MedGen UID:
341696
Concept ID:
C1857108
Finding
A reduction in the freedom of movement of one or more joints.
Cone-shaped epiphysis
MedGen UID:
351282
Concept ID:
C1865037
Finding
Cone-shaped epiphyses (also known as coned epiphyses) are epiphyses that invaginate into cupped metaphyses. That is, the epiphysis has a cone-shaped distal extension resulting from increased growth of the central portion of the epiphysis relative to its periphery.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Smooth philtrum
MedGen UID:
222980
Concept ID:
C1142533
Finding
Flat skin surface, with no ridge formation in the central region of the upper lip between the nasal base and upper vermilion border.
Short nose
MedGen UID:
343052
Concept ID:
C1854114
Finding
Distance from nasion to subnasale more than two standard deviations below the mean, or alternatively, an apparently decreased length from the nasal root to the nasal tip.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Thickened skin
MedGen UID:
66024
Concept ID:
C0241165
Finding
Laminar thickening of skin.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Professional guidelines

PubMed

Nguyen DB, Khirani S, Griffon L, Baujat G, Michot C, Marzin P, Rondeau S, Luscan R, Couloigner V, Pejin Z, Zerah M, Cormier-Daire V, Fauroux B
Am J Med Genet A 2021 Jul;185(7):2108-2118. Epub 2021 Apr 28 doi: 10.1002/ajmg.a.62236. PMID: 33908178
Marzin P, Thierry B, Dancasius A, Cavau A, Michot C, Rondeau S, Baujat G, Phan G, Bonnière M, Le Bourgeois M, Khraiche D, Pejin Z, Bonnet D, Delacourt C, Cormier-Daire V
Genet Med 2021 Feb;23(2):331-340. Epub 2020 Oct 21 doi: 10.1038/s41436-020-00994-x. PMID: 33082559
Allali S, Le Goff C, Pressac-Diebold I, Pfennig G, Mahaut C, Dagoneau N, Alanay Y, Brady AF, Crow YJ, Devriendt K, Drouin-Garraud V, Flori E, Geneviève D, Hennekam RC, Hurst J, Krakow D, Le Merrer M, Lichtenbelt KD, Lynch SA, Lyonnet S, MacDermot K, Mansour S, Megarbané A, Santos HG, Splitt M, Superti-Furga A, Unger S, Williams D, Munnich A, Cormier-Daire V
J Med Genet 2011 Jun;48(6):417-21. Epub 2011 Mar 17 doi: 10.1136/jmg.2010.087544. PMID: 21415077Free PMC Article

Recent clinical studies

Etiology

Marzin P, Thierry B, Dancasius A, Cavau A, Michot C, Rondeau S, Baujat G, Phan G, Bonnière M, Le Bourgeois M, Khraiche D, Pejin Z, Bonnet D, Delacourt C, Cormier-Daire V
Genet Med 2021 Feb;23(2):331-340. Epub 2020 Oct 21 doi: 10.1038/s41436-020-00994-x. PMID: 33082559
Cheng SW, Luk HM, Chu YWY, Tung YL, Kwan EY, Lo IF, Chung BH
Eur J Med Genet 2018 Apr;61(4):219-224. Epub 2017 Nov 27 doi: 10.1016/j.ejmg.2017.11.018. PMID: 29191498
McInerney-Leo AM, Le Goff C, Leo PJ, Kenna TJ, Keith P, Harris JE, Steer R, Bole-Feysot C, Nitschke P, Kielty C, Brown MA, Zankl A, Duncan EL, Cormier-Daire V
J Med Genet 2016 Jul;53(7):457-64. Epub 2016 Apr 11 doi: 10.1136/jmedgenet-2015-103647. PMID: 27068007
Allali S, Le Goff C, Pressac-Diebold I, Pfennig G, Mahaut C, Dagoneau N, Alanay Y, Brady AF, Crow YJ, Devriendt K, Drouin-Garraud V, Flori E, Geneviève D, Hennekam RC, Hurst J, Krakow D, Le Merrer M, Lichtenbelt KD, Lynch SA, Lyonnet S, MacDermot K, Mansour S, Megarbané A, Santos HG, Splitt M, Superti-Furga A, Unger S, Williams D, Munnich A, Cormier-Daire V
J Med Genet 2011 Jun;48(6):417-21. Epub 2011 Mar 17 doi: 10.1136/jmg.2010.087544. PMID: 21415077Free PMC Article
Le Goff C, Cormier-Daire V
Pediatr Endocrinol Rev 2009 Mar;6(3):418-23. PMID: 19396027

Diagnosis

Reyes-Hernández OD, Palacios-Reyes C, Chávez-Ocaña S, Cortés-Malagón EM, Alonso-Themann PG, Ramos-Cano V, Ramírez-Bello J, Sierra-Martínez M
BMC Musculoskelet Disord 2016 Feb 15;17:79. doi: 10.1186/s12891-016-0935-9. PMID: 26875674Free PMC Article
Le Goff C, Cormier-Daire V
Pediatr Endocrinol Rev 2009 Mar;6(3):418-23. PMID: 19396027
Giray O, Kýr M, Bora E, Saylam G, Ugurlu B, Gürel D
Ann Trop Paediatr 2008 Jun;28(2):161-4. doi: 10.1179/146532808X302206. PMID: 18510828
Rosser EM, Wilkinson AR, Hurst JA, McGaughran JM, Donnai D
Am J Med Genet 1995 Sep 11;58(3):217-21. doi: 10.1002/ajmg.1320580304. PMID: 8533820
Wraith JE, Bankier A, Chow CW, Danks DM, Sardharwalla IB
Am J Med Genet 1990 Feb;35(2):153-6. doi: 10.1002/ajmg.1320350202. PMID: 2090119

Therapy

Lee T, Takeshima Y, Okizuka Y, Hamahira K, Kusunoki N, Awano H, Yagi M, Sakai N, Matsuo M, Iijima K
Gene 2013 Jan 10;512(2):456-9. Epub 2012 Nov 2 doi: 10.1016/j.gene.2012.10.060. PMID: 23124041

Prognosis

Marzin P, Thierry B, Dancasius A, Cavau A, Michot C, Rondeau S, Baujat G, Phan G, Bonnière M, Le Bourgeois M, Khraiche D, Pejin Z, Bonnet D, Delacourt C, Cormier-Daire V
Genet Med 2021 Feb;23(2):331-340. Epub 2020 Oct 21 doi: 10.1038/s41436-020-00994-x. PMID: 33082559
Zhang A, Berardinelli SJ, Leonhard-Melief C, Vasudevan D, Liu TW, Taibi A, Giannone S, Apte SS, Holdener BC, Haltiwanger RS
J Biol Chem 2020 Nov 13;295(46):15742-15753. Epub 2020 Sep 10 doi: 10.1074/jbc.RA120.014557. PMID: 32913123Free PMC Article
Porayette P, Fruitman D, Lauzon JL, Le Goff C, Cormier-Daire V, Sanders SP, Pinto-Rojas A, Perez-Atayde AR
Pediatr Dev Pathol 2014 May-Jun;17(3):209-16. Epub 2013 Nov 19 doi: 10.2350/13-08-1370-CR.1. PMID: 24251637
Giray O, Kýr M, Bora E, Saylam G, Ugurlu B, Gürel D
Ann Trop Paediatr 2008 Jun;28(2):161-4. doi: 10.1179/146532808X302206. PMID: 18510828
Keret D, Lokiec F, Hayek S, Segev E, Ezra E
J Pediatr Orthop B 2002 Apr;11(2):100-3. doi: 10.1097/00009957-200204000-00003. PMID: 11943981

Clinical prediction guides

Camarena V, Williams MM, Morales AA, Zafeer MF, Kilic OV, Kamiar A, Abad C, Rasmussen MA, Briski LM, Peart L, Bademci G, Barbouth DS, Smithson S, Wang G, Shehadeh LA, Walz K, Tekin M
JCI Insight 2024 Feb 1;9(5) doi: 10.1172/jci.insight.174417. PMID: 38300707Free PMC Article
Zhang A, Berardinelli SJ, Leonhard-Melief C, Vasudevan D, Liu TW, Taibi A, Giannone S, Apte SS, Holdener BC, Haltiwanger RS
J Biol Chem 2020 Nov 13;295(46):15742-15753. Epub 2020 Sep 10 doi: 10.1074/jbc.RA120.014557. PMID: 32913123Free PMC Article
Hubmacher D, Taye N, Balic Z, Thacker S, Adams SM, Birk DE, Schweitzer R, Apte SS
Matrix Biol 2019 Sep;82:38-53. Epub 2019 Feb 7 doi: 10.1016/j.matbio.2019.02.001. PMID: 30738849Free PMC Article
Allali S, Le Goff C, Pressac-Diebold I, Pfennig G, Mahaut C, Dagoneau N, Alanay Y, Brady AF, Crow YJ, Devriendt K, Drouin-Garraud V, Flori E, Geneviève D, Hennekam RC, Hurst J, Krakow D, Le Merrer M, Lichtenbelt KD, Lynch SA, Lyonnet S, MacDermot K, Mansour S, Megarbané A, Santos HG, Splitt M, Superti-Furga A, Unger S, Williams D, Munnich A, Cormier-Daire V
J Med Genet 2011 Jun;48(6):417-21. Epub 2011 Mar 17 doi: 10.1136/jmg.2010.087544. PMID: 21415077Free PMC Article
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
Nat Genet 2008 Sep;40(9):1119-23. doi: 10.1038/ng.199. PMID: 18677313Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...