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Cutis laxa, autosomal dominant 1(ADCL1)

MedGen UID:
478169
Concept ID:
C3276539
Disease or Syndrome
Synonyms: ADCL1; ELN-Related Cutis Laxa
 
Gene (location): ELN (7q11.23)
 
Monarch Initiative: MONDO:0007411
OMIM®: 123700

Definition

FBLN5-related cutis laxa is characterized by cutis laxa, early childhood-onset pulmonary emphysema, peripheral pulmonary artery stenosis, and other evidence of a generalized connective disorder such as inguinal hernias and hollow viscus diverticula (e.g., intestine, bladder). Occasionally, supravalvar aortic stenosis is observed. Intrafamilial variability in age of onset is observed. Cardiorespiratory failure from complications of pulmonary emphysema (respiratory or cardiac insufficiency) is the most common cause of death. [from GeneReviews]

Additional description

From OMIM
Cutis laxa is a collection of disorders that are typified by loose and/or wrinkled skin that imparts a prematurely aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The skin lacks elastic recoil, in marked contrast to the hyperelasticity apparent in classic Ehlers-Danlos syndrome (see 130000). These properties are nearly always attributable to loss, fragmentation, or severe disorganization of dermal elastic fibers (summary by Davidson and Giro, 2002). Autosomal dominant congenital cutis laxa (ADCL) is genetically heterogeneous and shows clinical variability. The characteristic loose skin may be accompanied by gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema (summary by Graul-Neumann et al., 2008). Loose, inelastic skin is a clinical feature of many disorders, e.g., geroderma osteodysplasticum (GO; 231070) and Costello syndrome (218040). For a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see ARCL1A (219100). Genetic Heterogeneity of Autosomal Dominant Cutis Laxa Also see ADCL2 (614434), caused by mutation in the FBLN5 gene (604580) on chromosome 14q32, and ADCL3 (616603), caused by mutation in the ALDH18A1 (138250) gene on chromosome 10q24.  http://www.omim.org/entry/123700

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.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
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.
Peripheral pulmonary artery stenosis
MedGen UID:
138014
Concept ID:
C0345030
Finding
Stenosis of a peripheral branch of the pulmonary artery.
Inguinal hernia
MedGen UID:
6817
Concept ID:
C0019294
Finding
Protrusion of the contents of the abdominal cavity through the inguinal canal.
Uterine prolapse
MedGen UID:
22591
Concept ID:
C0042140
Finding
The presence of prolapse of the uterus.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.
Emphysema
MedGen UID:
18764
Concept ID:
C0034067
Disease or Syndrome
A subcategory of chronic obstructive pulmonary disease (COPD). It occurs in people who smoke and suffer from chronic bronchitis. It is characterized by inflation of the alveoli, alveolar wall damage, and reduction in the number of alveoli, resulting in difficulty breathing.
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
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.
Cutis laxa
MedGen UID:
8206
Concept ID:
C0010495
Disease or Syndrome
Wrinkled, redundant, inelastic and sagging skin.
Hyperextensible skin
MedGen UID:
66023
Concept ID:
C0241074
Finding
A condition in which the skin can be stretched beyond normal, and then returns to its initial position.
Redundant skin
MedGen UID:
154379
Concept ID:
C0581342
Pathologic Function
Loose and sagging skin often associated with loss of skin elasticity.
Poor wound healing
MedGen UID:
377525
Concept ID:
C1851789
Finding
A reduced ability to heal cutaneous wounds.
Prematurely aged appearance
MedGen UID:
346633
Concept ID:
C1857656
Finding
Progeroid facial appearance
MedGen UID:
341830
Concept ID:
C1857710
Finding
A degree of wrinkling of the facial skin that is more than expected for the age of the individual, leading to a prematurely aged appearance.

Recent clinical studies

Etiology

Okuneva EG, Kozina AA, Baryshnikova NV, Krasnenko AY, Tsukanov KY, Klimchuk OI, Surkova EI, Ilinsky VV
BMC Dermatol 2019 Jan 31;19(1):4. doi: 10.1186/s12895-019-0084-6. PMID: 30704477Free PMC Article

Diagnosis

Iancu ME, Albu AI, Albu DN
J Pediatr Endocrinol Metab 2022 Sep 27;35(9):1211-1214. Epub 2022 Jul 1 doi: 10.1515/jpem-2022-0054. PMID: 35770839
Okuneva EG, Kozina AA, Baryshnikova NV, Krasnenko AY, Tsukanov KY, Klimchuk OI, Surkova EI, Ilinsky VV
BMC Dermatol 2019 Jan 31;19(1):4. doi: 10.1186/s12895-019-0084-6. PMID: 30704477Free PMC Article

Therapy

Iancu ME, Albu AI, Albu DN
J Pediatr Endocrinol Metab 2022 Sep 27;35(9):1211-1214. Epub 2022 Jul 1 doi: 10.1515/jpem-2022-0054. PMID: 35770839

Clinical prediction guides

Iancu ME, Albu AI, Albu DN
J Pediatr Endocrinol Metab 2022 Sep 27;35(9):1211-1214. Epub 2022 Jul 1 doi: 10.1515/jpem-2022-0054. PMID: 35770839

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