Genodermatoses affecting the nail
Eckart Haneke in Histopathology of the NailOnychopathology, 2017
Werner syndrome (OMIM #277700) is a very rare autosomal recessive genetic instability and progeroid (“premature aging”) syndrome, which is associated with an elevated risk of cancer.206 It is caused by loss-of-function mutations in the WRN gene on chromosome 8p12 encoding a RecQ type helicase. Dermatologic signs are graying and loss of hair, scleroderma-like skin hardening due to loss of subcutaneous fat, and lower leg ulcers. Mottled and diffuse pigmentation may give the aspect of poikiloderma. The fingers may become sclerotic with glistening shiny atrophic tips.207,208 The nails become dystrophic or lost.209,210 Systemic alterations include cataracts, muscle atrophy, post-pubertal growth arrest, hoarseness, high-pitched voice, diabetes mellitus type 2, osteoporosis, hypogonadism, and severe atherosclerosis usually leading to death between the age of 40 and 60 years.211,212 Clinically, progeria may be mistaken for scleroderma.213 Severe acroosteolysis and nail dystrophy were also seen in another progeroid syndrome.214
Xeroderma Pigmentosum and Other DNA Repair-Deficient Photodermatoses
Henry W. Lim, Herbert Hönigsmann, John L. M. Hawk in Photodermatology, 2007
XP is a rare autosomal recessive genetic disease with an estimated prevalence of 1: 106 in the United States and Europe and 1: 105 in Japan. XP is characterized by an approximately 1000-fold increased risk to develop skin cancer (1,21). The first symptoms of XP often manifest in early childhood (Table 1). Some infants or small children with XP experience severe acute sunburn reactions after a short exposure of the skin to sunlight. This reaction can persist for several weeks. However, approximately half of the XP patients do not have this acute sun sensitivity. They tan and freckle without burning. Many of these patients are in XP complementation group C. Freckling of the face of a child less than two years old is unusual in normal children and is an indication that the diagnosis of XP should be considered. With continued sun exposure freckling of sun-exposed skin continues to develop into the typical appearance of poikiloderma with hypo- and hyperpigmentation, atrophy, and telangiectasias. These pigmentary changes in addition to dry (xerotic) skin are reflected in the name of the disease (Fig. 1).
Photoexacerbated Dermatoses
Henry W. Lim, Nicholas A. Soter in Clinical Photomedicine, 2018
Rothmund-Thomson syndrome is a syndrome of autosomal recessive inheritance that affects girls more often than boys (43). In his original description, Rothmund, an ophthalmologist, described a reticulate erythematous eruption progressing to hyperpigmentation with onset at 3–6 months of age, associated with juvenile cataracts (43). Similar cases, but without cataracts, were later described by Thomson under the name poikiloderma congenitale (44). Finally, Taylor concluded that the entities described by Rothmund and Thomson were the same (45). A review of 107 cases of the syndrome (46) showed that 33% of patients were photosensitive and 100% developed poikiloderma. Other features, in descending order of frequency included short stature (62%), absent or sparse scalp, eyelash, and eyebrow hair (60%), juvenile cataracts (47%), bony defects (42%), small hands (36%), hypogonadism (29%), defective dentition (27%), nail dystrophy (22%), and keratotic lesions (19%). The degree of photosensitivity ranged from immediate erythema to bulla formation. One patient was phototested and showed an increased sensitivity to UVA and a normal response to UVB.
Clinical practice guidance for juvenile dermatomyositis (JDM) 2018-Update
Published in Modern Rheumatology, 2020
Ichiro Kobayashi, Shinji Akioka, Norimoto Kobayashi, Naomi Iwata, Shunichiro Takezaki, Haruna Nakaseko, Satoshi Sato, Yutaka Nishida, Tomo Nozawa, Yuichi Yamasaki, Kazuko Yamazaki, Satoru Arai, Ichizo Nishino, Masaaki Mori
Heliotrope rash, Gottron’s papules, and Gottron’s sign are pathognomonic and tend to associate with disease activity, although Gottron’s sign may persist after achieving remission. The color of the heliotrope rash is rather dark reddish than purple in Japanese patients compared with Caucasians. Butterfly erythema which spreads over the cheeks on both sides of the root of the nose and often over the entire face is frequently an initial dermatological symptom of JDM. Inverse Gottron’s papules are frequently observed in adult patients with DM complicated with RP-ILD, whereas the correlation is not evident in JDM [15]. Periungual erythema is not specific but often observed as an initial symptom of JDM [16]. Elongation of the nail epithelium and dilated nail-fold capillaries are characteristic to both (J)DM and scleroderma. Poikiloderma is an intermix of pigmentation, depigmentation, dilatation of capillary vessels and skin atrophy in the same area, indicating chronic disease. Calcinosis is a characteristic cutaneous sign in JDM compared with DM [17]. Undermining ulcer is a possibly vasculitis-associated ulcerative lesion expanding from the dermis into subcutaneous tissues and associated with anti-MDA5 autoantibodies.
Clinical and genetic characteristics of nevus of Ota with choroidal melanoma in Chinese
Published in Ophthalmic Genetics, 2019
The exact etiology of nevus of Ota is still unknown. Although familial cases are rare, there may be an underlying genetic predisposition (13,14). Dr. Konstantinov found that GNAQ and BAP1 mutations in patients with nevus of Ota confer a greater risk for malignant melanoma and metastatic progression (7,15,16). In our series, we found two suspicious gene mutations involving FAM111B and DSC2 that might contribute to the etiology of the disease. The missense variants c.304T>C (p. Tyr102His) and c.2608G>C (p. Gly870Arg) were discovered in FAM111B and DSC2, respectively, according to our results. FAM111B is located in 11q12.1 and encodes a protein with a trypsin-like cysteine/serine peptidase domain in the C-terminus. Mutations in FAM111B are associated with hereditary fibrosing poikiloderma (HFP) (5). There is no current evidence to prove that FAM111B is associated with nevus of Ota. However, individuals with these gene mutations could display mottled pigmentation, which might indicate some relationship between FAM111B and nevus of Ota. DSC2, which is located in 18q12.1, encodes a member of the desmocollin protein subfamily. Mutations in this gene are associated with arrhythmogenic right ventricular dysplasia, reduced protein expression in several types of cancer, and tumor progression in esophageal cell carcinoma, gastric cancer, colon cancer, etc (6). No previous findings indicate whether DSC2 plays a role in nevus of Ota. DSC2 may be a new breakthrough for the disease. Further studies should identify the relationship between DSC2 and nevus of Ota.
Emerging drugs for the treatment of epidermolysis bullosa
Published in Expert Opinion on Emerging Drugs, 2020
Matthias Titeux, Mathilde Bonnet des Claustres, Araksya Izmiryan, Helene Ragot, Alain Hovnanian
KEB formerly known as Kindler syndrome has recently been classified as new subtype of EB [1]. This form is caused by recessive mutations in the FERMT1 gene coding for kindlin, a protein that functions in making up focal contact points of basal keratinocytes. The cleavage levels are multiple and can occur within keratinocytes, in the lamina densa and below the lamina densa, and are often associated with duplication of the basement membrane [11]. Patients present with epidermal skin fragility and blistering, photosensitivity and progressive poikiloderma, marked skin atrophy and periodontal disease.
Related Knowledge Centers
- Atrophy
- Dyskeratosis Congenita
- Hypopigmentation
- Telangiectasia
- Hyperpigmentation
- Poikiloderma Vasculare Atrophicans
- Poikiloderma of Civatte
- Hereditary Sclerosing Poikiloderma
- Rothmund–Thomson Syndrome
- Erythrokeratodermia Variabilis