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Cardiac valvular dysplasia, X-linked(CVDPX)

MedGen UID:
78083
Concept ID:
C0262436
Disease or Syndrome
Synonyms: Congenital valvular dysplasia; CVDPX; FLNA-Related X-linked Cardiac Valvular Dysplasia; Myxomatous valvular dystrophy, X-linked; Valvular heart disease, congenital
SNOMED CT: FLNA-related X-linked myxomatous valvular dysplasia (1186709006); Filamin A-related X-linked myxomatous valvular dysplasia (1186709006); FLNA-related valvular dystrophy (1186709006)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): FLNA (Xq28)
 
Monarch Initiative: MONDO:0010753
OMIM®: 314400
Orphanet: ORPHA555877

Disease characteristics

Excerpted from the GeneReview: FLNA Deficiency
FLNA deficiency is associated with a phenotypic spectrum that includes FLNA-related periventricular nodular heterotopia (Huttenlocher syndrome), congenital heart disease (patent ductus arteriosus, atrial and ventricular septal defects), valvular dystrophy, dilatation and rupture of the thoracic aortic, pulmonary disease (pulmonary hypertension, alveolar hypoplasia, emphysema, asthma, chronic bronchitis), gastrointestinal dysmotility and obstruction, joint hypermobility, and macrothrombocytopenia. [from GeneReviews]
Authors:
Ming Hui Chen  |  Christopher A Walsh   view full author information

Additional description

From OMIM
X-linked cardiac valvular dysplasia (CVDPX) is a rare form of heart disease characterized by multivalvular dysplasia and regurgitation, which can lead to lethal heart failure in some patients. Heterozygous females are more mildly affected than hemizygous males. Some patients also exhibit features of Ehler-Danlos syndrome (EDS; see 130000), with hyperextensible skin and joint hypermobility, whereas others have stiffening of joints from early childhood (Kyndt et al., 2007; Ritelli et al., 2017; Mercer et al., 2017).  http://www.omim.org/entry/314400

Clinical features

From HPO
Aortic regurgitation
MedGen UID:
8153
Concept ID:
C0003504
Disease or Syndrome
An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
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.
Tricuspid regurgitation
MedGen UID:
11911
Concept ID:
C0040961
Disease or Syndrome
Failure of the tricuspid valve to close sufficiently upon contraction of the right ventricle, causing blood to regurgitate (flow backward) into the right atrium.
Bicuspid aortic valve
MedGen UID:
57436
Concept ID:
C0149630
Congenital Abnormality
Aortic valve disease-2 (AOVD2) is characterized by bicuspid aortic valve (BAV) and dilation of the ascending aorta. Calcification of the valve and the aorta has been observed, and some patients exhibit coarctation of the aorta (Tan et al., 2012; Luyckx et al., 2019; Park et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of aortic valve disease, see AOVD1 (109730).
Short chordae tendineae of the mitral valve
MedGen UID:
868877
Concept ID:
C4023288
Anatomical Abnormality
Abnormally short chordae tendineae of the mitral valve.
Short chordae tendineae of the tricuspid valve
MedGen UID:
870553
Concept ID:
C4025001
Anatomical Abnormality
Abnormally short chordae tendineae of the tricuspid valve.
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.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
Thick vermilion border
MedGen UID:
332232
Concept ID:
C1836543
Finding
Increased width of the skin of vermilion border region of upper lip.
Prominent supraorbital ridges
MedGen UID:
333982
Concept ID:
C1842060
Finding
Greater than average forward and/or lateral protrusion of the supraorbital portion of the frontal bones.
Cutis laxa
MedGen UID:
8206
Concept ID:
C0010495
Disease or Syndrome
Wrinkled, redundant, inelastic and sagging skin.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
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).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVCardiac valvular dysplasia, X-linked
Follow this link to review classifications for Cardiac valvular dysplasia, X-linked in Orphanet.

Recent clinical studies

Diagnosis

Ma PH, Sachdeva R, Wilson EC, Guzzetta NA
Semin Cardiothorac Vasc Anesth 2016 Sep;20(3):240-5. Epub 2016 Mar 22 doi: 10.1177/1089253216640088. PMID: 27004951
Katsi V, Vlaseros I, Tsartsalis D, Souretis G, Tsioufis C, Kallikazaros I
Hellenic J Cardiol 2012 Sep-Oct;53(5):392-6. PMID: 22995611

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