| Cutis laxa | |
|---|---|
| Other names | Chalazoderma, Dermatochalasia, Dermatolysis, Dermatomegaly, Generalized elastolysis, Generalized elastorrhexis |
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| Cutis laxa in a neonate | |
| Specialty | Medical genetics  |
Cutis laxa [1] or pachydermatocele [2] is a group of rare connective tissue disorders in which the skin becomes inelastic and hangs loosely in folds. [3]
It is characterised by skin that is loose, hanging, wrinkled, and lacking in elasticity. The loose skin can be either generalised or localised. [4] Biopsies have shown reduction and degeneration of dermal elastic fibres in the affected areas of skin. [5] The loose skin is often most noticeable on the face, resulting in a prematurely aged appearance. The affected areas of skin may be thickened and dark. In addition, the joints may be loose (hypermobile) because of lax ligaments and tendons. When cutis laxa is severe, it can also affect the internal organs. The lungs, heart (supravalvular pulmonary stenosis), intestines, or arteries may be affected with a variety of severe impairments. In some cases, hernias and outpouching of the bladder can be observed. Patients can also present with whites of the eyes that are blue.[ citation needed ]
In many cases, cutis laxa is inherited. Autosomal dominant, autosomal recessive, and X-linked recessive forms have been described, but acquired forms also occur.[ citation needed ]
Cutis laxa is associated with deficient or absent elastin fibers in the extracellular matrix. [6] This can be related to decreased elastin synthesis or structural defects in the extracellular matrix. [7]
Cutis laxa may be caused by mutations in the genes: ELN, [8] ATP6V0A2 , [9] ATP7A, [10] FBLN4 , [11] FBLN5 , [12] and PYCR1 . [13] A related neurocutaneous syndrome may be caused by mutations in the gene ALDH18A1 (P5CS). [14] Cutis laxa may also be seen in association with inherited connective tissue disorders such as Ehlers–Danlos syndromes. Another syndrome associated with cutis laxa is Lenz-Majewski syndrome which is due to a mutation in the phosphatidylserine synthase 1 (PTDSS1) gene. [ citation needed ]
In contrast, acquired cutis laxa often has a triggering event such as urticaria, drugs (such as penicillin) or neoplasms. [15] Acquired cutis laxa may also be immunologically mediated, as it can involve dermal deposit of immunoglobulins and it can occur with autoimmune diseases. [5] Acquired cutis laxa has been associated with granular immunoglobulin A deposits as well as abundant neutrophils. [5] One hypothesis for the cause is excessive elastase release from neutrophils and macrophages. [15] It has also been considered that mutations in elastin (ELN) and fibulin-5 (FBLN5) genes can increase susceptibility of elastic fibres to inflammatory degradation in acquired cutis laxa. [15]
Acquired cutis laxa has also been seen in conjunction with a number of conditions including: rheumatoid arthritis, [16] systemic lupus erythematosus, [17] celiac disease, [5] and monoclonal gammopathies. [18] It can also occur as a postinflammatory response after urticaria. [19] Urticarial skin fibroblasts have shown a 2- to 3- fold increase in elastase activity in a patient with acquired cutis laxa. [20]
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As of 2019, there is no treatment for cutis laxa. Procedures aimed at mitigating symptoms and identifying subsequent conditions are often advised. No pharmacological agent has been able to stop the progression of the disease. [15] However, cosmetic surgeries are potentially an option as cutis laxa does not generally involve vascular fragility. [15]
Tietz syndrome, also called Tietz albinism-deafness syndrome or albinism and deafness of Tietz, is an autosomal dominant congenital disorder characterized by deafness and leucism. It is caused by a mutation in the microphthalmia-associated transcription factor (MITF) gene. Tietz syndrome was first described in 1963 by Walter Tietz (1927–2003) a German Physician working in California.
ICF syndrome is a very rare autosomal recessive immune disorder.
Palmoplantar keratodermas are a heterogeneous group of disorders characterized by abnormal thickening of the stratum corneum of the palms and soles.
Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections. It causes severe pyogenic infections. It can be caused by autosomal dominant inheritance of the ELANE gene, autosomal recessive inheritance of the HAX1 gene. There is an increased risk of leukemia and myelodysplastic cancers.
SCARF syndrome is a rare syndrome characterized by skeletal abnormalities, cutis laxa, craniostenosis, ambiguous genitalia, psychomotor retardation, and facial abnormalities. These characteristics are what make up the acronym SCARF. It shares some features with Lenz-Majewski hyperostotic dwarfism. It is a very rare disease with an incidence rate of approximately one in a million newborns. It has been clinically described in two males who were maternal cousins, as well as a 3-month-old female. Babies affected by this syndrome tend to have very loose skin, giving them an elderly facial appearance. Possible complications include dyspnea, abdominal hernia, heart disorders, joint disorders, and dislocations of multiple joints. It is believed that this disease's inheritance is X-linked recessive.
Papillon–Lefèvre syndrome (PLS), also known as palmoplantar keratoderma with periodontitis, is an autosomal recessive genetic disorder caused by a deficiency in cathepsin C.
Cerebrotendinous xanthomatosis, also called cerebral cholesterosis, is an autosomal recessive form of xanthomatosis. It falls within a group of genetic disorders called the leukodystrophies.
Naegeli–Franceschetti–Jadassohn syndrome (NFJS), also known as chromatophore nevus of Naegeli and Naegeli syndrome, is a rare autosomal dominant form of ectodermal dysplasia, characterized by reticular skin pigmentation, diminished function of the sweat glands, the absence of teeth and hyperkeratosis of the palms and soles. One of the most striking features is the absence of fingerprint lines on the fingers.
Uncombable hair syndrome (UHS) is a rare structural anomaly of the hair with a variable degree of effect. It is characterized by hair that is silvery, dry, frizzy, wiry, and impossible to comb. It was first reported in the early 20th century. It typically becomes apparent between the ages of 3 months and 12 years. UHS has several names, including pili trianguli et canaliculi (Latin), cheveux incoiffables (French), and "spun-glass hair". This disorder is believed to be autosomal recessive in most instances, but there are a few documented cases where multiple family members display the trait in an autosomal dominant fashion. Based on the current scientific studies related to the disorder, the three genes that have been causally linked to UHS are PADI3, TGM3, and TCHH. These genes encode proteins important for hair shaft formation. Clinical symptoms of the disorder arise between 3 months and 12 years of age. The quantity of hair on the head does not change, but hair starts to grow more slowly and becomes increasingly "uncombable". To be clinically apparent, 50% of all scalp hair shafts must be affected by UHS. This syndrome only affects the hair shaft of the scalp and does not influence hair growth in terms of quantity, textural feel, or appearance on the rest of the body.
Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive skin condition.
Woodhouse–Sakati syndrome, is a rare autosomal recessive multisystem disorder which causes malformations throughout the body, and deficiencies affecting the endocrine system.
Gerodermia osteodysplastica (GO) is a rare autosomal recessive connective tissue disorder included in the spectrum of cutis laxa syndromes.
Ichthyosis hystrix is a group of rare skin disorders in the ichthyosis family of skin disorders characterized by massive hyperkeratosis with an appearance like spiny scales. This term is also used to refer to a type of epidermal nevi with extensive bilateral distribution.
Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down into tricho – "hair", thio – "sulphur", and dystrophy – "wasting away" or literally "bad nourishment". TTD is associated with a range of symptoms connected with organs of the ectoderm and neuroectoderm. TTD may be subclassified into four syndromes: Approximately half of all patients with trichothiodystrophy have photosensitivity, which divides the classification into syndromes with or without photosensitivity; BIDS and PBIDS, and IBIDS and PIBIDS. Modern covering usage is TTD-P (photosensitive), and TTD.
Bart syndrome, also known as aplasia cutis congenita type VI, is a rare genetic disorder characterized by the association of congenital localized absence of skin, mucocutaneous blistering and absent and dystrophic nails.
Nakajo syndrome, also called nodular erythema with digital changes, is a rare autosomal recessive congenital disorder first reported in 1939 by A. Nakajo in the offspring of consanguineous parents. The syndrome can be characterized by erythema, loss of body fat in the upper part of the body, and disproportionately large eyes, ears, nose, lips, and fingers.
Wrinkly skin syndrome(WSS) is a rare genetic condition characterized by sagging, wrinkled skin, low skin elasticity, and delayed fontanelle (soft spot) closure, along with a range of other symptoms. The disorder exhibits an autosomal recessive inheritance pattern with mutations in the ATP6V0A2 gene, leading to abnormal glycosylation events. There are only about 30 known cases of WSS as of 2010. Given its rarity and symptom overlap with other dermatological conditions, reaching an accurate diagnosis is difficult and requires specialized dermatological testing. Limited treatment options are available but long-term prognosis is variable from patient to patient, based on individual case studies. Some skin symptoms recede with increasing age, while progressive neurological advancement of the disorder causes seizures and mental deterioration later in life for some patients.
De Barsy syndrome is a rare autosomal recessive genetic disorder. Symptoms include cutis laxa as well as other eye, musculoskeletal, and neurological abnormalities. It is usually progressive, manifesting side effects that can include clouded corneas, cataracts, short stature, dystonia, or progeria.
Focal facial dermal dysplasia is a rare genetically heterogeneous group of disorders that are characterized by congenital bilateral scar like facial lesions, with or without associated facial anomalies. It is characterized by hairless lesions with fingerprint like puckering of the skin, especially at the temples, due to alternating bands of dermal and epidermal atrophy.
Mendelian traits behave according to the model of monogenic or simple gene inheritance in which one gene corresponds to one trait. Discrete traits with simple Mendelian inheritance patterns are relatively rare in nature, and many of the clearest examples in humans cause disorders. Discrete traits found in humans are common examples for teaching genetics.