Novel Insights • The 2 related patients described here are the first prenatal presentations of ARCL1B. [karger.com]

The way in which the condition presents itself is different according to how it is inherited or acquired. Cutis laxa is also known as generalised elastolysis. [dermnetnz.org]

The infant presented in the above clinical case had novel homozygous mutation in PYCR1 gene which is likely pathogenic variant of autosomal recessive cutis laxa type 2B/3B [3]. PYCR1 gene helps in synthesis of proline from glutamate. [link.springer.com]

The index patient presented with seizures and generalized hypotonia. [idoj.in]

Clinical presentation and mode of inheritance show considerable heterogeneity; autosomal dominant, autosomal recessive, and X-linked recessive forms have been reported. [jamanetwork.com]

• Developmental Delay

  ARCL II is represented by a spectrum of clinical phenotype with variable severity of cutis laxa, abnormal growth, and developmental delay. [idoj.in]

  Affected individuals may experience growth delays, developmental delays, failure to thrive, intellectual disability, joint laxity and skeletal malformations. [rarediseases.org]

  In view of the frequent occurrence of microcephaly, the mild–moderate developmental delay is most likely central in origin. [nature.com]

  Other symptoms associated with cutis laxa include: developmental delays eyes that are further apart than is typical feeding difficulties in infants fragile bones lax or loose joints low-set ears or ears that aren’t properly formed poor muscle tone short [healthline.com]

  Neurological findings typically observed include developmental delay, intellectual disability, hypotonia, microcephaly, hearing loss, seizures, and a cobble-like dysgenesis demonstrated by MRI of the brain [4,5,6]. [mdpi.com]

• Short Stature

  Additional symptoms include: short stature sparse hair cutis laxa Acquired Cutis Laxa Some people have symptoms, but don’t have the genetic changes associated with cutis laxa. This type of cutis laxa is known as acquired cutis laxa. [healthline.com]

  Short stature and open fontanel are common findings in cutis laxa types 2A and 2B, but occur less frequently in GO (Table 2); however, in our patients ¾ showed short stature. [mdpi.com]

  Joint laxity, hernias, frequent hip dislocations, and varying degrees of growth deficiency and short stature can also occur. Osteoporosis may also present, resulting in fragile bones that are prone to fracture. [rarediseases.org]

• Respiratory Distress

  Affected individuals may develop severe breathing difficulties (respiratory distress) associated with cystic changes in the lungs as well as collapse of part of the lung (atelectasis). [rarediseases.org]

• Failure to Thrive

  Affiliated tissues include cortex and heart, and related phenotypes are failure to thrive and cataract Disease Ontology : 12 An autosomal recessive cutis laxa type II classic type that is characterized by generalized skin wrinkling with sparse subcutaneous [malacards.org]

  Infants may experience diminished muscle tone (hypotonia), abnormal fat distribution, feeding difficulties, growth deficiency, and failure to thrive. [rarediseases.org]

  Systemic involvement includes failure to thrive due to chronic diarrhea, malabsorption, congenital hydronephrosis, urethral and bladder diverticulae. [nature.com]

• Heart Failure

  In severe cases, the various vascular and cardiac abnormalities can progress to cause heart failure. [rarediseases.org]

• High Arched Palate

  ATS features include elongation, tortuosity and aneurysms of major arteries, cutis laxa, joint laxity, hernias, long slender face, and high-arched palate. [karger.com]

• Low Set Ears

  Other symptoms associated with cutis laxa include: developmental delays eyes that are further apart than is typical feeding difficulties in infants fragile bones lax or loose joints low-set ears or ears that aren’t properly formed poor muscle tone short [healthline.com]

  Child had dysmorphism in the form of sagging cheeks, maxillary hypoplasia, prognathism, posteriorly placed large and low set ears, hypertelorism, down slanting palpebral fissures, wide open anterior fontanelle, medial epicanthal folds, depressed nose, [idoj.in]

• Cutis Laxa

  MalaCards organs/tissues related to Cutis Laxa, Autosomal Recessive, Type Iid: 40 Cortex, Heart [malacards.org]

  Discriminative features in three autosomal recessive cutis laxa syndromes: cutis laxa IIA, cutis laxa IIB, and geroderma osteoplastica. Int J Mol Sci. 2017;18(3):635. [link.springer.com]

  We observed cutis laxa, arachnodactyly, clinodactyly, camptodactyly, clubfoot, and micrognathia (Fig. 1E). [karger.com]

  Additional symptoms include: short stature sparse hair cutis laxa Acquired Cutis Laxa Some people have symptoms, but don’t have the genetic changes associated with cutis laxa. This type of cutis laxa is known as acquired cutis laxa. [healthline.com]

  Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica. Int J Mol Sci. 2017 Mar 15. 18 (3):[Medline]. [emedicine.medscape.com]

• Eczema

  It may occur spontaneously or in 50% of cases develop following episodes of urticaria or angioedema, extensive inflammatory skin disease (e.g. eczema, erythema multiforme, blistering eruption), or hypersensitivity reactions to penicillin or other drugs [dermnetnz.org]

  […] diaphragmatic hernia, and emphysema leading to cor pulmonale and death in the first few years of life. [8, 9] Approximately one half of the cases of acquired cutis laxa (elastolysis) are associated with a preceding inflammatory eruption, such as urticaria, eczema [emedicine.medscape.com]

• Hip Dislocation

  dislocation and characteristic facies, is described. [onlinelibrary.wiley.com]

  Hypotonia and congenital hip dislocation are also found in all three conditions, but the severity and frequency of these findings varies. [mdpi.com]

  dislocation, spinal curvature) Emphysema (lung disease causing breathlessness) Hernias Diverticula (outpouching) in the oesophagus, duodenum and bladder Aortic aneurysm (bulging aorta, the main artery leaving the heart) Type I: Severe form Present at [dermnetnz.org]

  Joint laxity, hernias, frequent hip dislocations, and varying degrees of growth deficiency and short stature can also occur. Osteoporosis may also present, resulting in fragile bones that are prone to fracture. [rarediseases.org]

  Associated cranial anomalies, late closure of the fontanel, joint laxity, hip dislocation and inguinal hernia have been observed, but uncommon. [nature.com]

• Bowing of The Long Bones

  Skeletal malformations may include sideways curvature of the spine (scoliosis), bowing of the long bones of the arms and legs, clasped thumbs, abnormally long fingers and toes, reduced bone density (osteopenia), fragile bones that are prone to fracture [rarediseases.org]

• Joint Dislocation

  + + + + + +/− +/− + + + + + − Dislocations − − + - − + − − − − − Adducted thumbs − − + + + + + − + − − − Clenched hands − − + + − − + − + − − − Increased palmar creases + + + + + + + + + + Wrinkled skin + + + + + + + + + + + + + Severe wrinkling of skin [mdpi.com]

• Psychomotor Retardation

  Neurological Features The neurological findings common to ARCL2A and ARCL2B patients are intellectual disability, hypotonia, psychomotor retardation, microcephaly, and seizures. [mdpi.com]

We suggest a simple and practical diagnostic approach for the workup of patients with a suspected autosomal recessive cutis laxa (Figure 5). [nature.com]

What is the treatment for cutis laxa? There is no specific treatment for cutis laxa or preventing the progression of the disease. Treatment is directed at managing any complications that may arise from associated internal organ involvement. [dermnetnz.org]

Treatments for cutis laxa depend on your symptoms. A team of specialists — including cardiologists, pulmonologists, dermatologists, and surgeons — may treat the condition. Cosmetic surgery can tighten skin that is loosened due to cutis laxa. [healthline.com]

The causes of acquired cutis laxa are unclear, although it may occur as a side effect of treatment with medications that remove copper from the body (copper chelating drugs). [medlineplus.gov]

Additional symptoms may eventually develop including dystonia, a group of movement disorders that vary in their symptoms, causes, progression, and treatments. [rarediseases.org]

[…] gammopathy following treatment of a nodal plasmacytoma. Arch Dermatol. 2011 Mar. 147(3):323-8. [Medline]. O'Malley JT, D'Agati VD, Sherman WH, Grossman ME. [emedicine.medscape.com]

Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. [rarediseases.org]

Prognosis The lifespan of some patients with cutis laxa (elastolysis) may not be significantly decreased. Patients with the autosomal dominant form have a normal life expectancy. [emedicine.medscape.com]

The presence of the metabolic alteration has consequences both for organ involvement, prognosis assessment and counselling. [nature.com]

In cutis laxa patients mutations have been demonstrated in elastin or fibulin genes, but in the majority of patients the underlying genetic etiology remains unknown. [nature.com]

Epidemiology Frequency Cutis laxa (elastolysis) is rare. Congenital forms of cutis laxa (elastolysis) are more common than acquired disease. The recessively inherited form is most frequent and most severe. Autosomal dominant forms also exist. [emedicine.medscape.com]

Pathophysiology Cutis laxa (elastolysis) is characterized by degenerative changes in the elastic fibers resulting in loose, pendulous skin. The skin is sagging, redundant, and stretchable, with reduced elastic recoil. [emedicine.medscape.com]

Pathophysiological aspects in ARCL type II patients with a ATP6V0A2 defect As described above, a large number of families with ARCL type II or WSS2, 22 with a distinct phenotype showed loss-of-function mutations in the a2-subunit of the V-type H+-ATPase [nature.com]

You can’t prevent cutis laxa because it’s a genetic condition. Acquired cutis laxa can’t be prevented because doctors currently don’t know the exact cause of it. [healthline.com]

There is no specific treatment for cutis laxa or preventing the progression of the disease. Treatment is directed at managing any complications that may arise from associated internal organ involvement. [dermnetnz.org]

In addition, some subtypes of cutis laxa have only been reported in a handful of individuals, which prevents physicians from developing a complete picture of associated symptoms and prognosis. [rarediseases.org]

In the follow up, one should emphasize the importance of caloric intake, developmental assessment, physiotherapy and evaluation of possible osteoporosis to prevent frequent fractures in some of the ARCL II and GO patients. [nature.com]