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American Journal of Medical Genetics.... Oct 2022POIKiloderma, tendon contractures, myopathy, pulmonary fibrosis is a congenital multisystem disorder due to FAM111B dominant variants. We present a literature review... (Review)
Review
Expanding phenotype of FAM111B-related disease focusing on liver involvement: Literature review, report of a case with end-stage liver disease and proposal for a new acronym.
POIKiloderma, tendon contractures, myopathy, pulmonary fibrosis is a congenital multisystem disorder due to FAM111B dominant variants. We present a literature review focusing on the frequency and the impact of hepatic involvement and a case report of a patient with severe end-stage liver disease. Whole exome sequencing (WES) was conducted on the proband and his parents. A de novo FAM111B: c.1879A > G; (p.Arg627Gly) variant was identified. Hepatic involvement is present in 11 out of the 30 patients described in the literature, with different levels of dysfunction ranging from mild transaminitis to liver fibrosis found in three different cases by liver biopsies. Liver involvement seems to be a significant cause of morbidity. We propose to modify the previous acronym in POIK-TMPL: including POIKiloderma, tendon contractures, myopathy, pulmonary fibrosis/pancreas insufficiency and cancer, liver involvement/lymphedema. Moreover, we suggest screening patients with FAM111B variants for liver involvement from the first month of life and continue with an appropriate follow-up. Further studies are needed to better understand this frequent complication.
Topics: Atrophy; Cell Cycle Proteins; Contracture; End Stage Liver Disease; Humans; Muscular Diseases; Pancreatic Diseases; Phenotype; Pulmonary Fibrosis; Skin Abnormalities
PubMed: 35869874
DOI: 10.1002/ajmg.a.62906 -
Frontiers in Oncology 2022gene mutations are associated with a hereditary fibrosing poikiloderma known to cause poikiloderma, tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP). In... (Review)
Review
gene mutations are associated with a hereditary fibrosing poikiloderma known to cause poikiloderma, tendon contracture, myopathy, and pulmonary fibrosis (POIKTMP). In addition, the overexpression of FAM111B has been associated with cancer progression and poor prognosis. This review inferred the molecular function of this gene's protein product and mutational dysfunction in fibrosis and cancer based on recent findings from studies on this gene. In conclusion, FAM111B represents an uncharacterized protease involved in DNA repair, cell cycle regulation, and apoptosis. The dysregulation of this protein ultimately leads to fibrotic diseases like POIKTMP and cancers the disruption of these cellular processes by the mutation of the gene. Hence, it should be studied in the context of these diseases as a possible therapeutic target.
PubMed: 35860584
DOI: 10.3389/fonc.2022.932167 -
Indian Journal of Ophthalmology Jul 2022We aimed describe the chronic ocular sequelae of Kindler syndrome. All cases of Kindler syndrome with ocular involvement that presented to a tertiary eye care center...
We aimed describe the chronic ocular sequelae of Kindler syndrome. All cases of Kindler syndrome with ocular involvement that presented to a tertiary eye care center were included. Three cases of Kindler syndrome with ocular changes were reviewed. Case 1 (10 years, female) had recurrent epithelial breakdown with severe dry eye and corneal opacity secondary to keratitis. Case 2 (28 years, male) had symblepharon , ocular surface keratinization , and severe dry eye. Case 3 (16 years , female ) had partial limbal stem cell deficiency with dry eye. All cases were treated with topical lubricants, short course of low-potency steroids and immuno-modulators. Attention must be paid to the eye in addition to the oro-an-genital mucosa to avoid longterm ocular sequelae.
Topics: Adult; Blister; Child; Disease Progression; Epidermolysis Bullosa; Eye; Eye Diseases; Face; Female; Humans; Male; Periodontal Diseases; Photosensitivity Disorders
PubMed: 35791162
DOI: 10.4103/ijo.IJO_791_22 -
Familial Cancer Jan 2023Rothmund-Thomson syndrome, a heterogeneous genodermatosis with autosomal recessive hereditary pattern, is an uncommon cancer susceptibility genetic syndrome. To date,...
Rothmund-Thomson syndrome, a heterogeneous genodermatosis with autosomal recessive hereditary pattern, is an uncommon cancer susceptibility genetic syndrome. To date, only 400 cases have been reported in the literature, and the severity of the features varies among individuals with the condition. Here, we describe a 55-year-old male who had been diagnosed with Bloom Syndrome during childhood due to the suggestive physical features such as short stature, chronic facial erythema, poikiloderma in face and extremities, microtia and microcephaly. However, the genetic test demonstrated that the patient carried two pathogenic variants resulting in compound heterozygous in the RECQL4 gene (c.2269C>T and c.2547_2548delGT). He subsequently developed a calcaneal osteosarcoma, which was successfully treated, and has currently been oncologic disease-free for 3 years.
Topics: Male; Humans; Middle Aged; Rothmund-Thomson Syndrome; RecQ Helicases; Bloom Syndrome
PubMed: 35781852
DOI: 10.1007/s10689-022-00303-2 -
Cureus May 2022Kindler syndrome is a rare autosomal recessive skin disorder. It results from mutation of the FERM domain containing kindlin-1 (FERMT1) that leads to loss of function of...
Kindler syndrome is a rare autosomal recessive skin disorder. It results from mutation of the FERM domain containing kindlin-1 (FERMT1) that leads to loss of function of kindlin-1, which plays a role in keratinocyte adhesion, polarization, proliferation, and migration. It is characterized by skin blistering, photosensitivity, progressive poikiloderma, and skin atrophy. The mucosae genitourinary system is commonly affected. The urological manifestations include meatal stenosis, urethral stricture, phimosis, and scarring of the glans penis. Skin biopsy with genetic analysis is the gold standard for diagnosis. Genetic counseling and a multidisciplinary approach are the mainstays of treatment.
PubMed: 35676982
DOI: 10.7759/cureus.24758 -
Pediatrics International : Official... Jan 2022Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma of the face, small stature, sparse scalp hair, juvenile...
BACKGROUND
Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma of the face, small stature, sparse scalp hair, juvenile cataract, radial aplasia, and predisposition to cancers. Due to the rarity of RTS, the situation of patients with RTS in Japan has not been elucidated.
METHODS
In 2010 and 2020, following the results of a primary questionnaire survey, a secondary questionnaire survey on RTS was conducted nationwide to investigate the number of RTS cases and their associated skin lesions, bone lesions, other clinical features, and quality of life in Japan.
RESULTS
In 2010 and 2020, 10 and eight patients with RTS were recruited, respectively. Skin lesions such as poikiloderma, erythema, pigmentation, and abnormal scalp hair were observed in almost all cases. Bone lesions were observed in four cases in the 2010 and 2020 surveys, respectively. Two cases had mutations in the RECQL4 gene in the 2020 survey.
CONCLUSIONS
Two nationwide surveys have shown the actual situation of patients with RTS in Japan. Cutaneous and bone manifestations are important for the diagnosis of RTS. However, many patients have no RECQL4 mutations. The novel causative gene of RTS should be further elucidated.
Topics: Humans; Japan; Mutation; Quality of Life; Rothmund-Thomson Syndrome; Surveys and Questionnaires
PubMed: 35616152
DOI: 10.1111/ped.15120 -
Frontiers in Genetics 2022Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is an extremely rare disease caused by mutations in FAM111B, and...
Case Report: Hereditary Fibrosing Poikiloderma With Tendon Contractures, Myopathy, and Pulmonary Fibrosis (POIKTMP) Presenting With Liver Cirrhosis and Steroid-Responsive Interstitial Pneumonia.
Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is an extremely rare disease caused by mutations in FAM111B, and only approximately 30 cases have been reported worldwide. Some patients develop interstitial pneumonia, which may lead to progressive pulmonary fibrosis and poor prognosis. However, no effective treatment for interstitial pneumonia associated with POIKTMP has been reported. Here, we report an autopsy case of POIKTMP, wherein interstitial pneumonia was improved by corticosteroids. A 44-year-old Japanese man was referred to our hospital due to poikiloderma, hypotrichosis, and interstitial pneumonia. He developed progressive poikiloderma and muscle weakness since infancy. He also had tendon contractures, short stature, liver cirrhosis, and interstitial pneumonia. Mutation analysis of FAM111B revealed a novel and heterozygous missense mutation, c.1886T > G (p(Phe629Cys)), through which we were able to diagnose the patient with POIKTMP. 3 years after the POIKTMP diagnosis, interstitial pneumonia had worsened. After 2 weeks of administrating 40 mg/day of prednisolone, his symptoms and lung shadows improved. However, he subsequently developed severe hepatic encephalopathy and eventually died of respiratory failure due to bacterial pneumonia and pulmonary edema. Autopsy revealed an unclassifiable pattern of interstitial pneumonia, as well as the presence of fibrosis and fatty degeneration in several organs, including the liver, kidney, skeletal muscle, heart, pancreas, and thyroid. We report a case of POIKTMP in which interstitial pneumonia was improved by corticosteroids, suggesting that corticosteroids could be an option for the treatment of interstitial pneumonia associated with this disease.
PubMed: 35601499
DOI: 10.3389/fgene.2022.870192 -
Zhongguo Yi Xue Ke Xue Yuan Xue Bao.... Apr 2022Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS....
Objective To investigate the clinical characteristics and genetic mutations in Kindler syndrome(KS)and provide a theoretical basis for the diagnosis and treatment of KS. Methods The clinical data of one case of KS from Peking Union Medical College Hospital and 185 cases reported in literature were collected. The gene mutation types,patient clinical data,and tumor characteristics were statistically analyzed. Results A total of 186 cases were enrolled,including 110 males and 76 females,with the mean age of(28±16)years. The data of gene mutation and specific clinical manifestations were available in 151 and 94 patients,respectively. The main clinical manifestations of KS included poikiloderma,occurrence of blister in childhood,and photosensitivity,and the secondary clinical manifestations included oral inflammation,palmoplantar keratoderma,webbing/pseudoainhum,dysphagia,urethral stricture and so on.Oral inflammation(=0.234,=0.023),palmoplantar keratoderma(=0.325,=0.001),webbing/pseudoainhum(=0.247,=0.016),dysphagia(=0.333,=0.001),urethral stricture(=0.280,=0.006)were significantly correlated with age,showing significantly higher incidence in the patients over 32 years old.Urethral stricture(=11.292,=0.001)and anal stenosis(=4.014,=0.045)were significantly correlated with sex,with higher incidence in males.Eighty different mutations were found in 151 patients,and the most common gene mutation was c.676C>T.Forty-one tumors occurred in 27 patients,among which squamous cell carcinoma accounted for 92.7%. The gene mutation site had no significant correlation with squamous cell carcinoma or patient country. Conclusions The c.676C>T in FERMT1 gene is the most common mutation in KS.The patients are prone to squamous cell carcinoma and mainly attacked at the exposure sites(hand and mouth).
Topics: Adolescent; Adult; Ainhum; Blister; Carcinoma, Squamous Cell; Child; Constriction, Pathologic; Deglutition Disorders; Epidermolysis Bullosa; Female; Humans; Inflammation; Keratoderma, Palmoplantar; Male; Membrane Proteins; Mutation; Neoplasm Proteins; Periodontal Diseases; Photosensitivity Disorders; Urethral Stricture; Young Adult
PubMed: 35538757
DOI: 10.3881/j.issn.1000-503X.14761 -
Pediatric Dermatology Jul 2022Two siblings presented with sun sensitivity and progressive dyspigmentation. A diagnosis of xeroderma pigmentosum was initially favored due to XPC mutations, although...
Two siblings presented with sun sensitivity and progressive dyspigmentation. A diagnosis of xeroderma pigmentosum was initially favored due to XPC mutations, although variants were not clearly diagnostic. However, new moderate neutropenia and homozygous suspected pathogenic variants in USB1 led to diagnosis of poikiloderma with neutropenia. This case highlights the importance of reevaluation of diagnosis due to significant phenotypic overlap in congenital disorders of photosensitivity with poikiloderma or dyspigmentation.
Topics: Connective Tissue Diseases; Homozygote; Humans; Mutation; Neutropenia; Phosphoric Diester Hydrolases; Skin Abnormalities
PubMed: 35522049
DOI: 10.1111/pde.15007 -
Drugs in Context 2022Early recognition of xeroderma pigmentosum is important to minimize the complications arising from the harmful effects of exposure to ultraviolet radiation. This... (Review)
Review
BACKGROUND
Early recognition of xeroderma pigmentosum is important to minimize the complications arising from the harmful effects of exposure to ultraviolet radiation. This narrative review aims to familiarize physicians with the clinical features, diagnosis and management of xeroderma pigmentosum.
METHODS
A search was conducted in December 2021 in PubMed Clinical Queries using the key term "xeroderma pigmentosum". The search strategy included all clinical trials, observational studies and reviews published within the past 10 years. The information retrieved from the search was used in the compilation of this article.
RESULTS
Xeroderma pigmentosum is a condition of abnormal DNA repair of ultraviolet radiation-induced and oxidative DNA damage, which leads to increased skin cancer susceptibility. Approximately 50% of patients with xeroderma pigmentosum have increased photosensitivity and certain types of xeroderma pigmentosum are more prone to ocular disease and progressive neurodegeneration depending on the causative mutation. The diagnosis should be suspected in patients with increased photosensitivity and characteristic cutaneous, ophthalmological and neurological findings. A definite diagnosis can be made by the identification of biallelic mutation in one of the causative genes. Strict and consistent sun avoidance and protection and early detection and treatment of premalignant and malignant skin lesions are the mainstays of management. Treatment options for actinic keratosis include cryotherapy, topical imiquimod, topical 5-fluorouracil, chemical peeling, excision, CO laser resurfacing, fractional/pulsed laser therapy, and photodynamic therapy. Cutaneous malignancy can be treated by photodynamic therapy, curettage and electrodesiccation, or surgical excision. Oral isotretinoin, oral niacinamide, topical imiquimod and topical fluorouracil can be used for the prevention of skin malignancy. Treatment options for poikiloderma include chemical peeling, dermabrasion and laser resurfacing. Methylcellulose eyedrops and soft ultraviolet-protective contact lenses may be used to keep the cornea moist and protect against the harmful effects of keratitis sicca. Investigational therapies include the use of T4 endonuclease-V liposome lotion and oral nicotinamide to reduce the rate of actinic keratoses and non-melanoma skin cancers and gene therapy for radical cure of this condition.
CONCLUSION
Although currently there is no cure for xeroderma pigmentosum, increased awareness and early diagnosis of the condition, followed by rigorous sun avoidance and protection and optimal management, can dramatically improve the quality of life and life expectancy.
PubMed: 35520754
DOI: 10.7573/dic.2022-2-5