Cutis laxa syndrome

Classification according to ICD-10
Q82.8	Other specified congenital malformations of the skin - cutis laxa (hyperelastica)
ICD-10 online (WHO version 2019)

Under Cutis Laxa ( lat. For "loose skin") refers to a heritable or acquired disease of the connective tissue with wrinkled, hanging and sagging inelastic skin .

At this point only the syndromes are listed as congenital forms, all others including diagnostics and differential diagnosis can be found under the conceptual synonym Dermatochalasis .

distribution

The frequency is given as about 1 in 1,000,000, so far about 200 patients have been described.

root cause

The aetiology of the hereditary forms is apparently very heterogeneous ; a number of genes involved have been identified in those affected .

Classification

Currently, according to the type of inheritance and clinical picture, a distinction is made between the following forms:

Autosomal recessive (ARCL)

The forms with autosomal - recessive inheritance (ARCL) are further subdivided into

• ARCL1 (cutis laxa, autosomal recessive, type 1) as the most severe form with life-threatening complications .

According to the location of the mutations found so far, there is a further division into:

• • ARCL1A with mutations in the FBLN5 gene at location 14q32.12
  • ARCL1B with mutations in the EFEMP2 gene at location 11q13.1
  • ARCL1C Cutis laxa with severe concomitant abnormalities of the lungs, gastrointestinal tract and urinary tract or Urban-Rifkin-Davis syndrome with mutations in the LTBP4 gene at location 19q13.2

• ARCL2 (cutis laxa, autosomal recessive, type 2) with a combination of cutis laxa, joint instability and developmental delay.

These are diseases with a wide range of clinical abnormalities, some of which overlap in the genetic changes found. The PYCR1-associated cutis laxa is one of the congenital segmental progeroid syndromes (rare hereditary diseases in which signs of premature aging - see also progeria - show in more than one organ or tissue).

• • Wrinkly skin syndrome with wrinkled skin disease with mutations in the ATP6V0A2 gene at location 12q24.31
  • Classic form of the Debré type with more severe changes, growth retardation and skeletal abnormalities. Mutations in the ATP6V0A2 and PYCR1 genes were found at location 12q24.3 and 17q25.3, respectively.
  • ARCL2A Cutis laxa, autosomal recessive, type 2A
  • ARCL2B Cutis laxa, autosomal recessive, type 2B or progeroid form with mutations in the PYCR1 gene at location 17q25.3

• • ARCL3A or De Barsy Syndrome A (cutis laxa - corneal opacity - mental retardation)
  • ARCL3B or De Barsy Syndrome B (Cutis laxa, autosomal recessive, type IIIB) with mutations in the PYCR1 gene at location 17q25.3

Autosomal Dominant (ADCL)

The autosomal dominant inherited form ( ADCL ) is considered a comparatively less serious skin disease, but hernias , changes in the heart valves , diverticula in the gastrointestinal tract or emphysema can occur.

According to the mutations found, a further division can be made into:

• ADCL1 with mutations in the elastin gene ELN at location 7q11.23
• ADCL2 with mutations in the fibulin-5 gene FBLN5 at location 14q32.12.

X-linked (XRCL)

The occipital horn syndrome (Cutis Laxa, X-linked) is an X-linked inherited and clinically similar to ARCL2.

(Outdated) synonyms are: EDS IX, Ehlers-Danlos syndrome type 9.

There are mutations in the ATP7A gene at location Xq21.1

Complex malformations

A cutis laxa in combination with other malformations can be found in:

• Cutis-laxa-marfanoid syndrome or neonatal form of cutis laxa with a marfanoid phenotype
• MACS syndrome (macrocephaly, alopecia, cutis laxa, scoliosis) or RIN2 syndrome with mutations in the RIN2 gene at location 20p11.23
• Menkes syndrome
• Sakati-Nyhan syndrome (cutis laxa- osteoporosis ), the Akrozephalopolysyndaktylien duly
• Geroderma osteodysplastica
• Scarf syndrome (skeletal anomaly, cutis laxa, craniostenosis, ambiguity of the genitals , retardation and facial abnormalities)

Prospect of healing

The prognosis depends very much on the respective form, it ranges from usually fatal course already in childhood with the ARCL1 to normal life expectancy with the lighter forms.

Individual evidence

1. ↑ ^{a b c d} Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
2. ^ Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
3. ↑ ARCL1A.  In: Online Mendelian Inheritance in Man . (English)
4. ↑ ARCL1B.  In: Online Mendelian Inheritance in Man . (English)
5. ↑ ARCL1C.  In: Online Mendelian Inheritance in Man . (English)
6. ↑ Davor Lessel, Christian Kubisch: Genetically determined syndromes with signs of premature aging. In: Deutsches Ärzteblatt. Volume 116, Issue 29 f., July 22, 2019, pp. 489–496, here: pp. 489–492.
7. ^ Wrinkly skin syndrome.  In: Online Mendelian Inheritance in Man . (English)
8. ^ Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
9. ^ Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
10. ^ Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
11. ↑ ARCL2B.  In: Online Mendelian Inheritance in Man . (English)
12. ↑ ARCL3A.  In: Online Mendelian Inheritance in Man . (English)
13. ↑ ARCL3B.  In: Online Mendelian Inheritance in Man . (English)
14. ^ Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
15. ↑ ADCL1.  In: Online Mendelian Inheritance in Man . (English)
16. ↑ ADCL2.  In: Online Mendelian Inheritance in Man . (English)
17. ^ Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
18. ^ Occipital horn syndrome.  In: Online Mendelian Inheritance in Man . (English)
19. ^ Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
20. ↑ CUTIS LAXA, NEONATAL, WITH MARFANOID PHENOTYPE.  In: Online Mendelian Inheritance in Man . (English)
21. ^ Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
22. ^ MACS Syndrome.  In: Online Mendelian Inheritance in Man . (English)
23. ^ Cutis laxa syndrome. In: Orphanet (Rare Disease Database).
24. ↑ Scarf Syndrome. In: Orphanet (Rare Disease Database).
25. ↑ Scarf Syndrome.  In: Online Mendelian Inheritance in Man . (English)

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !