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Indian Journal of Dermatology Nov 2014Familial poikiloderma-like cutaneous amyloidosis(FPLCA) is a rare, generalized but genetic dyschromic skin disorder characterized by amyloid deposits in dermis due to...
Familial poikiloderma-like cutaneous amyloidosis(FPLCA) is a rare, generalized but genetic dyschromic skin disorder characterized by amyloid deposits in dermis due to defective DNA repair secondary to sunlight damage. Clinically, it presents with diffuse brownish pigmentation with hypo-pigmented macules and many brownish scattered lichenoid papules with normal developmental milestones. The condition is autosomal dominant with incomplete penetrance. We are here reporting a rare familial case of FPLCA with a review of the literature.
PubMed: 25484425
DOI: 10.4103/0019-5154.143581 -
Scientific Reports Oct 2018Systemic sclerosis (SSc) is a prototypic systemic fibrotic disease with unclearly characterized genetic basis. We have discovered that mutations in family with sequence...
UNLABELLED
Systemic sclerosis (SSc) is a prototypic systemic fibrotic disease with unclearly characterized genetic basis. We have discovered that mutations in family with sequence similarity 111, member B (FAM111B) gene cause hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis, a multisystem fibrotic condition with clinical similarities to SSc. This observation has established FAM111B as a candidate gene for SSc.
PATIENTS AND METHODS
Demographic and clinical characteristics of consenting adults with definite SSc were recorded. Blood DNA analysis was performed using the High-Resolution Melt technique, and samples with abnormal electropherograms were selected for Sanger sequencing to identify mutations. Ethnically-matched controls from the general South African population were used to verify the frequency of variants in FAM111B. Public databases such as 1000 Genomes and ExAC were also used to verify the frequency of variants in FAM111B.
RESULTS
Of 131 patients, 118 (90.1%) were female, and 78 (59.5%) were black Africans. Genetic analysis revealed two FAM111B genetic variants. The c.917 A > G variant (rs200497516) was found in one SSc patients, and one control, and was classified as a missense variant of unknown significance. The c.988 C > T variant (rs35732637) occurred in three SSc patients and 42/243 (17.3%) of healthy controls, and is a known polymorphism.
CONCLUSION
One rare variant was found in a patient with SSc but has no functional or structural impact on the FAM111B gene. In this cohort, FAM111B gene mutations are not associated with SSc.
Topics: Adult; Aged; Alleles; Biomarkers; Cell Cycle Proteins; Computational Biology; Cross-Sectional Studies; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Mutation; Phenotype; Radiography, Thoracic; Scleroderma, Systemic; Tomography, X-Ray Computed
PubMed: 30375432
DOI: 10.1038/s41598-018-34341-7 -
Indian Journal of Dermatology Nov 2014Subacute cutaneous lupus erythematosus (SCLE) is a type of lupus erythematosus having distinct characteristic clinical, serologic, and genetic features. Other than the...
Subacute cutaneous lupus erythematosus (SCLE) is a type of lupus erythematosus having distinct characteristic clinical, serologic, and genetic features. Other than the commonly occurring papulosquamous and annular polycyclic lesion, rarely it may present as erythema multiformae, toxic epidermo necrolysis like lesion (Rowell syndrome), erythroderma, and generalized poikiloderma. Herein, we report a case of SCLE presenting as erythroderma.
PubMed: 25484433
DOI: 10.4103/0019-5154.143589 -
Special Care in Dentistry : Official... Jul 2016Kindler syndrome is a rare genetic disorder showing some predominant clinical manifestations, for example, trauma-induced blisters, progressive poikiloderma, skin... (Review)
Review
Kindler syndrome is a rare genetic disorder showing some predominant clinical manifestations, for example, trauma-induced blisters, progressive poikiloderma, skin atrophy, and photosensitivity. Oral manifestations are not commonly described and can be often misdiagnosed. This report describes the case of a female patient diagnosed with Kindler syndrome showing the classical clinical features affecting the skin, in addition to oral lesions manifesting as keratotic plaques and ulcers affecting the buccal mucosa, floor of the mouth, alveolar ridge, hard palate, and soft palate. An incisional biopsy was performed to confirm the diagnostic hypothesis of an autoimmune lesion possibly related with the syndrome. Knowledge about the possible manifestations of the Kindler syndrome is important to improve its management.
Topics: Blister; Epidermolysis Bullosa; Female; Humans; Middle Aged; Mouth Diseases; Periodontal Diseases; Photosensitivity Disorders
PubMed: 26815761
DOI: 10.1111/scd.12165 -
Boletin Medico Del Hospital Infantil de... 2022Rothmund-Thomson syndrome, also known as congenital poikiloderma, is a rare autosomal recessive genodermatosis with onset in early childhood that affects at a...
BACKGROUND
Rothmund-Thomson syndrome, also known as congenital poikiloderma, is a rare autosomal recessive genodermatosis with onset in early childhood that affects at a multisystem level.
CASE REPORTS
Case 1. A 4-year-old male patient, consanguineous parents, 26-year-old brother with a probable diagnosis of Rothmund-Thompson syndrome. He presented with adactyly of the right thumb, hypoplasia of the left thumb, delayed growth and psychomotor development. At 3 months, he presented rough, dry, sparse hair and erythematous lesions on the face, leaving hyperpigmented and hypopigmented spots with a reticulated pattern. We detected hypoacusis, skeletal alterations, narrow chin, short stature, severe malnutrition, and chronic and asymptomatic hypodontia. Genetic sequencing showed a mutation for the RECQL4 gene, for which a multidisciplinary follow-up was provided by the genetics, gastroenterology, nutrition, endocrinology, stomatology, audiology, orthopedics, rehabilitation, ophthalmology and oncology services. Case 2. A 2-year-old female patient presented facial erythema that spread to the arms and legs at 3 months; skin biopsy showed poikiloderma. She was evaluated by the endocrinology service and followed up for short stature and hypogonadism. A genetic study was not performed.
CONCLUSIONS
Rothmund-Thomson syndrome is characterized by atrophy. Only a few cases are reported in the literature. We present two cases of Rothmund-Thomson syndrome, emphasizing its clinical and dermatological characteristics.
Topics: Adult; Child; Child, Preschool; Female; Hospitals, Pediatric; Humans; Male; Mexico; Mutation; Rothmund-Thomson Syndrome
PubMed: 35086131
DOI: 10.24875/BMHIM.21000013 -
Human Molecular Genetics Aug 2017Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk...
Rothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder characterized by poikiloderma, small stature, sparse hair, skeletal abnormalities, increased risk of osteosarcoma, and decreased bone mass. To date, there has not been a comprehensive evaluation of the prevalence and extent of metabolic bone disease in RTS. Furthermore, the mechanisms that result in this phenotype are largely unknown. In this report, we provide a detailed evaluation of 29 individuals with RTS with respect to their metabolic bone status including bone mineral density, calcium kinetics studies, and markers of bone remodeling. We show that individuals with RTS have decreased areal bone mineral density. Additionally, we demonstrate that the presence of pathogenic variants in RECQL4 and low bone mineral density correlate with the history of increased risk of fractures. Using a RECQL4-deficient mouse model that recapitulates skeletal abnormalities seen in individuals with RTS, we demonstrate that generalized skeletal involvement is likely due to decreased osteogenesis. Our findings are clinically relevant as they may help in the risk stratification of patients with RTS and also in the identification of individuals who may benefit from additional surveillance and management of metabolic bone disease.
Topics: Adult; Animals; Bone Density; Bone Remodeling; Child; Child, Preschool; Female; Fractures, Bone; Humans; Male; Mice; Mutation; Osteogenesis; RecQ Helicases; Risk Factors; Rothmund-Thomson Syndrome
PubMed: 28486640
DOI: 10.1093/hmg/ddx178 -
Dermatology (Basel, Switzerland) 2020Poikilodermatous mycosis fungoides (pMF) is characterized by poikiloderma areas, typically involving the major flexural areas and trunk. Its presentation can be... (Comparative Study)
Comparative Study
BACKGROUND
Poikilodermatous mycosis fungoides (pMF) is characterized by poikiloderma areas, typically involving the major flexural areas and trunk. Its presentation can be generalized or admixed with other forms of MF. Previous studies fail to correlate the clinical presentation with prognosis and laboratory findings. Some reports show pityriasis lichenoides chronica (PLC) preceding the poikiloderma.
OBJECTIVES
Correlate prognostic, histopathological and molecular aspects of pMF with its clinical presentation.
METHODS
Retrospective analysis of 14 cases of generalized pMF (GpMF), 22 of localized pMF (LpMF) and 17 of pMF admixed with other forms of MF (mix-pMF).
RESULTS
Female predominance and lower age at diagnosis was found in all groups compared to classic MF, a high prevalence of PLC-like lesions in the GpMF group and a high rate of hypopigmented lesions in the mix-pMF group. There were 2 deaths within the GpMF group. Histology was similar to previously reported findings, as was the prevalence of CD4 T-cell infiltrate, compared to CD8. The T-cell clonality positivity was lower in the GpMF group, compared to other groups (27% GpMF, 80% LpMF and 100% mix-pMF).
DISCUSSION
This is the first article to categorize the different forms of pMF and correlate them with clinical and laboratory findings. The dermatological presentation differs among the groups. There was a high frequency of PLC-like lesions within the GpMF group and of hypopigmented lesions in mix-pMF. The histological and immunohistochemical findings were similar to those previously reported. Aggressive treatments are not recommended due to the good prognosis of all pMF forms. The low positivity of T-cell clonality in the GpMF group should be investigated.
Topics: Clone Cells; Female; Humans; Immunohistochemistry; Male; Middle Aged; Mycosis Fungoides; Parapsoriasis; Prognosis; Retrospective Studies; Skin Neoplasms; T-Lymphocytes
PubMed: 31550709
DOI: 10.1159/000502027 -
JPMA. the Journal of the Pakistan... Aug 2017Breast Cancer (BC) has associated risk factors and genetic factors like BRCA1, and BRCA2. Many benign and malignant disease processes are found concurrently with BC and...
Breast Cancer (BC) has associated risk factors and genetic factors like BRCA1, and BRCA2. Many benign and malignant disease processes are found concurrently with BC and believed to be additional risk factors like gall bladder stones (cholelithiasis), hypertension, diabetes mellitus, cerebrovascular lesions, arthritis, spine and spinal cord degenerative lesions, infertility, depression, sleep disturbances, obesity, autoimmune diseases (SLE), and thyroid diseases. There are some malignant disease associations like synchronous or metachronous ovarian, colonic and endometrial tumours with Breast cancer. Kindler Syndrome (KS) is a rare autosomal recessive genetic disorder manifesting as generalized dermatoses, described in 1954 by Theresa Kindler. KS is associated with acral skin blistering inducible by trauma, mucosal inflammation, photosensitivity, progressive pigmentation, telangiectasia, and skin atrophy (Poikiloderma). Repeated and progressive inflammation and subsequent fibrosis leads to ectropion, esophageal, anal, urethral, and vaginal stenosis and dryness. About 100 cases of Kindler syndrome have been reported in literature so far some from Arab World as well. Pathobiology of Kindler syndrome is not well understood. There are defects in KIND1 gene on chromosome 20. This gene expresses itself in basal keratinocytes, where it encodes a protein, called Kindlin 1. We report the second only case of Kindler's syndrome having breast cancer. These very very rare combinations have diagnostic issues, management restrictions, prognostic and follow up implications.
Topics: Adult; Antineoplastic Agents, Hormonal; Blister; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Chemotherapy, Adjuvant; Epidermolysis Bullosa; Female; Humans; Mastectomy; Mastectomy, Segmental; Neoplasm Staging; Neoplasm, Residual; Oman; Periodontal Diseases; Photosensitivity Disorders; Sentinel Lymph Node Biopsy; Tamoxifen
PubMed: 28839322
DOI: No ID Found -
Indian Journal of Dermatology,... 2021Mycosis fungoides is the most common form of cutaneous T-cell lymphoma. Narrowband ultraviolet B and psoralen and ultraviolet A are effective treatment options, but...
BACKGROUND
Mycosis fungoides is the most common form of cutaneous T-cell lymphoma. Narrowband ultraviolet B and psoralen and ultraviolet A are effective treatment options, but studies of their treatment efficacy and disease relapse remain limited.
OBJECTIVES
This study aimed (1) to determine the efficacy of narrowband ultraviolet B and psoralen and ultraviolet A as a treatment for early-stage mycosis fungoides and explore the predictive factors for complete remission and (2) to determine the relapse rate and analyze their predictive factors, including the utility of maintenance therapy.
METHODS
This was a retrospective cohort study consisting of 61 patients with early-stage mycosis fungoides (IA - IB) treated with narrowband ultraviolet B or psoralen and ultraviolet A as the first-line therapy from January 2002 to December 2018 at the Division of Dermatology, Ramathibodi Hospital, Bangkok, Thailand. Cox regression analysis and Kaplan-Meier survival curve were performed for the main outcomes.
RESULTS
A complete remission was achieved by 57 (93.5%) patients. The median time to remission was 7.80 ± 0.27 months. Types of phototherapy (narrowband ultraviolet B or psoralen and ultraviolet A), age and gender did not associate with time to remission, while the presence of poikiloderma and higher disease stage led to a longer time to remission. The cumulative incidence of relapse was 50.8%. The median time to relapse was 24.78 ± 5.48 months. In patients receiving phototherapy during the maintenance period, a treatment duration longer than six months was associated with a significantly longer relapse-free interval.
CONCLUSION
Narrow-band-ultraviolet B and psoralen and ultraviolet A are effective treatment options for early-stage mycosis fungoides. Maintenance treatment by phototherapy for at least six months seems to prolong remission.
Topics: Adult; Female; Ficusin; Glucocorticoids; Humans; Male; Mycosis Fungoides; Neoplasm Recurrence, Local; Photosensitizing Agents; Phototherapy; Remission Induction; Retrospective Studies; Skin Neoplasms
PubMed: 33871205
DOI: 10.25259/IJDVL_555_19 -
Calcified Tissue International Apr 2023Progressive osseous heteroplasia (POH) is a rare, debilitating disorder characterized by heterotopic ossification in the skin and muscles, resulting in contractures of...
INTRODUCTION
Progressive osseous heteroplasia (POH) is a rare, debilitating disorder characterized by heterotopic ossification in the skin and muscles, resulting in contractures of the joints and progressive loss of function. While 60-70% of the POH patients have paternally inherited, inactivating pathogenic variants in GNAS, the remaining 30-40% have no known etiology. FAM111B pathogenic variants, located on chromosome 11q12.1, cause POIKTMP (hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis), a very rare, autosomal-dominant disorder with high frequency of de novo missense pathogenic variants, which affects multiple tissues and organs, causing extensive fibrosis and muscle adiposis, though the exact mechanism is unknown. To our knowledge, there are no reports of FAM111B associated with POH. We describe the first case of POH phenotype associated with a novel de novo frameshift pathogenic variant in the FAM111B and present an analysis of the protein structure and function caused by this genomic disruption.
CASE
A 15-year-old African-American male presented with generalized calcific nodules, progressive contractures, and muscle weakness leading to immobility, beginning at 6 years of age. Cutaneous examination showed generalized hard nodules varying from small to plaque-like ulcerated erupted skin lesions. Biochemical evaluation revealed 25(OH) vitamin D insufficiency (20 ng/mL), and normal levels of parathyroid hormone, FGF-23, alkaline phosphatase, calcium, and phosphorus. Skeletal survey radiographs and computed tomography (CT) of the chest, abdomen, and pelvis showed extensive soft tissue and muscle heterotopic ossifications involving shoulders, axillae, trunk, abdomen, pelvis, upper and lower extremities, in a clumped, conglomerate distribution within muscle, subcutaneous fat, and in some areas extending to the skin. There was no pulmonary fibrosis on the chest CT. The clinical and radiographic findings were most consistent with POH. A trio-clinical exome sequencing revealed a de novo heterozygous likely pathogenic variant in the FAM111B (OMIM # 615584) (c.1462delT [p.Cys488Valfs*21]). The resulted frameshift change in exon 4 replaced C-terminal region with 21 alternative amino acids. Multiple, previously reported disease-associated variants appear to localize within the trypsin-like cysteine/serine peptidase domain in which this variant occurs, supporting the functional significance of this region, though none have been previously reported to be associated with POH phenotype. Our 3D protein modeling showed obliteration of predicted protein folding and structure, and elimination of the zinc-binding domain, likely severely affecting protein function.
CONCLUSION
This is the first case of POH phenotype associated with a novel de novo pathogenic frameshift variant in FAM111B. Whether the frameshift change in FAM111B predicts POH remains unclear. Further evaluations are necessary to fully elucidate this finding and the potential role and mechanism by which the FAM111B variants contributes to POH phenotype.
Topics: Male; Humans; GTP-Binding Protein alpha Subunits, Gs; Ossification, Heterotopic; Phenotype; Contracture; Fibrosis; Cell Cycle Proteins
PubMed: 36575358
DOI: 10.1007/s00223-022-01053-0