Hypertrichosis Research Articles

Chromosome 8 Inversion Mutation in Congenital Generalized Hypertrichosis: Precise Breakpoints Localization.

We reported a three-generation family with congenital generalized hypertrichosis (CGH), identifying an inversion variant on chr 8: inv(8)(q24.13q24.3) through comprehensive genetics analysis. Our report enriches the spectrum of CGH and its mutation profile.

Acquired Hypertrichosis Lanuginosa Associated with Lung Carcinoma

Hypertrichosis lanuginosa acquisita (HLA) is an acquired condition most of ten associated with medication use and endocrine or metabolic disorders. The association of HLA with malignancy has been also noted. Here in we report a case of HLA revealing a lung carcinoma.

Exome sequencing reveals the first intragenic deletion in ABCA5 underlying autosomal recessive hypertrichosis.

Hereditary hypertrichosis (HH) is characterized by excessive hair growth on various body areas, which is independent of the individual's age. This rare hair disorder has been classified by its origin (genetic or acquired), age of onset, breadth of hair distribution (universal or localized) and the affected body areas. HH is often linked to several additional congenital abnormalities involving teeth, heart and bones. Human HH is associated with heterozygous genomic duplications and deletions in the chromosomal region 17q24.2-q24.3, containing genes such as ABCA5, ABCA6, ABCA10 and MAP2K6. Recently, a homozygous splice-site variant in ABCA5 has been reported to cause autosomal recessive congenital generalized hypertrichosis terminalis (CGHT; OMIM 135400). To investigate the clinical and genetic basis of autosomal recessive hypertrichosis in a large consanguineous Pakistani family. In the present study, we characterized a family of Pakistani origin segregating CGHT in an autosomal recessive pattern, using whole exome sequencing followed by Sanger sequencing RESULTS: We identified a novel 2-bp intragenic deletion [NM_172232.4(ABCA5);c.977_978delAT] causing a frameshift variant (p.His326ArgfsTer5) in ABCA5. To our knowledge, this is the first intragenic deletion in ABCA5 underlying CGHT. The findings further validate the involvement of ABCA5 in hair development. The study will facilitate genetic counselling of families carrying CGHT-related features in Pakistani and other populations.

A rare clinical image of hypertrichosis (Werewolf syndrome)

Hypertrichosis refers to enormous hair growth over the body. It is a rare condition in which the hair can cover the entire face and body or can occur in small patches. It can affect both men and women. There are several types of acquired hypertrichosis, nevoid hypertrichosis, congenital hypertrichosis lanuginosa, congenital hyertrichosis terminalis and hirsutism. These disorders can have either vellus, lanugo or terminal type of hair. There has not been any specific etiology, but it could be linked to porphyria cutanea tarda, androgenic steroids, lichen simplex, or malnutrition. Also, medications such as minoxidil, phenytoin, and cyclosporin have been linked to abnormal hair growth. Since there is no specific treatment, it can only be managed through epilation, shaving, electrolysis, or laser surgery. A 10-year-old male child approached with a patch of dark hair over the face that was present since birth. His clinical and medical history was not significant. On examination, the hair was dense, and thick and indicated a terminal type of growth. The child had low self-esteem and was also hesitant to talk about the problem. Since there have been very few cases around the globe there is limited research data for the treatment of this disorder it becomes necessary to guide such patients and boost their morals so that they could spend their lives like normal human beings.

Hypertrichosis and blisters in an infant.

Hypertrichosis and blisters in an infant.

Large, violaceous tumor with hyperhidrosis and hypertrichosis.

Large, violaceous tumor with hyperhidrosis and hypertrichosis.

Capryloyl glycine and soy isoflavonoids in hypertrichosis: An experimental and placebo-controlled clinical study.

BackgroundThe management of acquired hypertrichosis (HT) is based on the search of the causes and subsequent specific treatment. However, simultaneous hair removal is important. No single method for hair removal is appropriate for all patients and skin areas. Treatment options are actually limited and clinical results are often unsatisfactory. Ornithine decarboxylase 1 (ODC1), an enzyme present in hair follicles, is considered as a potential target to inhibit hair growth. Only eflornithine hydrochloride, an inhibitor of ODC1, showed to be partially effective in the management of acquired HT.AimsThe aim of our study was to evaluate the potential inhibition of ODC1 activity by a cream containing 4% capryloyl glycine, an ODC1 inhibitor, and 1% glycine soy‐fermented extract (soy isoflavonoids). Furthermore, we present the results of a placebo‐controlled clinical study that evaluated the efficacy and tolerability of this cream.MethodsThe ODC1 activity was detected by measuring absorbance at 340 nm. In the presence of ODC1 inhibitors, absorbance decreases as a function of inhibition. Difluoromethylornithine (DFMO) was provided as an inhibitor control. ODC1 activity inhibition was expressed as percentage of control (untreated sample). All data were presented as mean ± standard deviation of three independent experiments. To determine if statistically significant differences between treatments were present, a t test analysis was performed. The differences between groups were considered significant at p < 0.05. Twelve Caucasian female adult patients, with HT located on the forearms, were enrolled. The study cream (product A) was applied twice/day for four months on the right forearm. A placebo cream (product B) was applied twice/day for four months on the left forearm. Clinical efficacy was evaluated by means of macrophotography.ResultsThe cream significantly inhibited ODC1 activity (35.1 ± 0.5% inhibition, equivalent to a 64.9 ± 0.5% ODC1 activity). DFMO completely abolished the enzymatic activity (100 ± 5% inhibition, equivalent to 0 ± 5% ODC1 activity). All patients were considered evaluable. In 11 out of 12 patients (91.7%), who were treated with product A, an improvement was observed. No improvement was observed in patients treated with product B. The global assessment showed good efficacy in 7 patients (58.3%) and moderate efficacy in 5 patients (41.7%) treated with the product A. No efficacy was detected in patients treated with product B.ConclusionsThe study cream showed to be effective in Caucasian, adult, female patients with hypertrichosis located on the forearms.

Cyclosporine-induced childhood generalized hypertrichosis

Cyclosporine-induced childhood generalized hypertrichosis

Dermatological paraneoplastic syndromes in gastroenterology: prediction of the inevitable or guidance to action? Part II

The second part of the article provides considerations for the proliferative and inflammatory dermatoses accompanying various malignant tumors of digestive organs. The most widespread paraneoplastic syndromes (PNS) have been described, including the acquired hypertrichosis lanuginosa, malignant black acanthosis, acquired padermatoglyphia, which, as a rule, accompany and sometimes lead to the appearance of malignant neoplasms of the gastrointestinal tract and lungs. The high probability has been emphasized for the diagnosis of benign black acanthosis in patients with obesity, insulin resistance, diabetes mellitus, patients taking medications for a long time. The authors presented typical manifestations of rarer PNS: paraneoplastic acrokeratosis, circular migrating erythema, paraneoplastic dermatomyositis. The detailed information provided regarding Leser — Trélat syndrome, which described the relationship between the appearance of numerous seborrheic keratomas and the development of malignant internal organ neoplasms. The possible relationship between Leser — Trélat syndrome and malignant black acanthosis was highlighted.The authors presented a clinical case with typical manifestations of dermatological PNS (Leser — Trélat syndrome) in a patient with a serous pancreatic cystadenoma. Despite the extremely low probability of malignant transformation of this neoplasm, the rapid growth of a pancreatic cyst (atypical for a benign formation) with simultaneous increase in the number and size of seborrheal adenoma was observed during medical observation. The results of 2‑year observation of the patient after the prophylactic pancreas resection have been outlined.

Hypertrichosis after medicine mix-up in Spain

Hypertrichosis after medicine mix-up in Spain

Paraneoplastische Hauterkrankungen

Various specific skin alterations can occur in patients with malignant diseases. If these skin diseases occur as associated symptoms of amalignant process, they are called paraneoplastic. In this overview, obligate and frequent facultative paraneoplastic skin diseases are assigned according to the triggering type of malignancy. Some of the processes predominantly show alink with malignant diseases of the digestive tract, e.g. acanthosis nigricans, florid cutaneous papillomatosis, necrolytic migratory erythema, Leser-Trélat syndrome, palmoplantar keratoderma, panniculitis and pityriasis rubra pilaris. Others are predominantly associated with ahematolymphoid malignoma, e.g. acquired ichthyosis, exfoliative erythroderma, necrobiotic xanthogranuloma, paraneoplastic pemphigus, plane xanthoma, pyoderma gangrenosum, scleromyxedema, Sweet syndrome and leukocytoclastic vasculitis. In athird group paraneoplastic skin diseases are pooled in association with other malignancies, e.g. Trousseau's syndrome, dermatomyositis, erythema gyratum repens, hypertrichosis lanuginosa acquisita and papuloerythroderma of Ofuji. In order to initiate targeted diagnostics for detection of an underlying malignant disease, it is essential that accomplished physicians recognize the skin diseases that represent obligate or potential paraneoplasms as such.

Cutaneous paraneoplastic syndromes

A variety of cutaneous abnormalities can be seen in patients with malignant diseases, some of which are infectious, with others representing direct involvement of the skin by the underlying disorder. Yet another group of lesions can be regarded as associated markers of the malignant process, and, as such, are termed "paraneoplastic." This review considers the latter collection of conditions, grouping them by the generic type of malignancy that is usually linked to the paraneoplasia. Some of the processes show a predominant association with alimentary tract malignancies (acanthosis nigricans, acrodermatitis paraneoplastica, florid cutaneous papillomatosis, necrolytic migratory erythema, palmoplantar keratoderma, pancreatic fat necrosis, and pityriasis rotunda). Others are usually linked to a hematolymphoid malignancy (acquired ichthyosis, exfoliative erythroderma, necrobiotic xanthogranuloma, pemphigus paraneoplastica, plane xanthoma, pyoderma gangrenosum, scleromyxedema, Sweet syndrome, and leukocytoclastic vasculitis). Finally, yet another collection of paraneoplastic skin disorders can associate themselves with anatomically-diverse malignancies (Leser-Trelat syndrome, Trousseau syndrome, dermatomyositis, erythema gyratum repens, hypertrichosis lanuginosa acquisita, papuloerythroderma of Ofuji, tripe palms, and multicentric reticulohistiocytosis). Recognition of these processes by the pathologist can be a valuable step in the characterization of underlying malignant diseases.

Wiedemann-Steiner syndrome caused by novel mutation of KMT2A gene: one case report and literature review

Objective To analyze the clinical and biochemical, as well as genetic characteristics of a patient with Wiedemann-Steiner syndrome (WDSTS). Methods The clinical data of a patient with WDSTS were collected. The patient was treated with recombinant human growth hormone (rhGH) combined with gonadotrophine-releasing hormone agonist (GnRHa). Blood samples of the patient and her parents were taken for whole-Exome Sequencing (WES). Relevant literatures about KMT2A mutations were reviewed. Results The 5-year old girl presented with growth retardation, with height 100 cm (-2.4 SD), torpid reaction, and facial anomalies including low hairline, thick eyebrow and hair, hypertelorism, a wide nasal bridge. She had small and puffy hands and feet, excessive hair around back of neck, bilateral forearm and lower limbs. Her GH peak level was 26.6 ng/ml during GH stimulation test. She was re-examined at the age of 10.4 years, with severe short stature (120 cm/-3.58 SD) and a Tanner stage 2 of breast development. Her bone age was found to be approximately 11.4 years. Height increased from 120 cm at the age of 10.4 years to 147.3 cm after rhGH treatment combined with GnRHa for 2.5 years. rhGH therapy alone continued for 1.1 years and a height of 150 cm was reached at the age of 14.9 years, with bone age 14 years. Gene sequencing revealed a de novo frameshift mutation (c.10051delA, p. Thr3351Leufs*17) of exon 27 in KMT2A gene of the patient, but without any mutation in her parents. Through a literature review, seventy-one patients with WDSTS (including present case) presented with intellectual disability(70/71), facial anomalies (70/71), short stature (50/71), and hypertrichosis(39/71). Conclusion Patients presented with short stature, typical facial dysmorphism, intellectual disability, and hypertrichosis should be considered for WDSTS. The mutation p. Thr3351Leufs*17 in the KMT2A gene detected in our patient is a novel mutation. This is so far the first report of WDSTS patient who was successfully treated with a combination of GH and GnRHa at the onset of puberty to improve her adult height. Key words: Wiedemann-Steiner syndrome; KMT2A gene; Short stature; Hypertrichosis; Therapy

Cutaneous manifestations in neonates: A 1-year cross-sectional study in a tertiary care hospital

BACKGROUND: Skin lesions in neonatal period range from transient self-limiting conditions to serious dermatoses requiring specific therapies. They can cause significant psychological distress to parents. The awareness of the fact that most of these conditions are benign and transient is important so that parents can be reassured. Since studies on neonatal dermatoses are limited, this study has been planned to know the spectrum of cutaneous lesions in neonates, both physiological and pathological.MATERIALS AND METHODS: All neonates <28 days old, attending KLEs Dr. Prabhakar Kore Hospital and MRC, Belgaum, were recruited into the study. Newborns admitted in the Neonatal Intensive Care Unit were excluded from the study. A written informed consent was obtained from the mother. The study design was nonrandomized cross-sectional study. A sample size calculation was done using the Chi-square test. Analysis of data was performed by STATA 11.2. An Ethical Committee clearance was obtained before the start of the study.RESULTS: One hundred and four neonates were enrolled in the study, out of which 49 (47%) neonates were male and 55 (53%) were female. Fifty-one (49%) neonates were born through normal vaginal delivery and 53 (51%) by cesarean section. Three (2.88%) neonates were born preterm, 5 (4.81%) post-term, and 96 (92.31%) neonates were born at term. Ninty-nine (95%) had physiological changes and 5 (5%) had pathological changes. The most common physiological change observed was mongolian spot in 34 (33%) of neonates followed by erythema toxicum neonatorum in 27 (26%) neonates and physiological desquamation in 21 (20%). Other less common physiological skin changes observed were milia, miliaria, hypertrichosis lanuginosa, vernix caseosa, and sebaceous gland hyperplasia. Pathological skin changes were observed in only five neonates, out of which one had bullous impetigo, one had birth trauma, 1 had furunculosis, 1 had intertrigo, and 1 was a collodion baby.CONCLUSION: Skin changes in newborn are very common. However, majority are physiological and transient requiring no treatment.

Segmental Odontomaxillary Dysplasia in a Pediatric Patient: Case Report

Segmental Odontomaxilar dysplasia is an uncommon pathology development that defects in the maturation of bone, teeth and gingiva one of the quadrants of the maxilla. Dentoalveolar expansion presents complex on the affected side with gingival enlargement, agenesis of one or two premolars, delayed eruption and malformation of the molars. Mucocutaneous upper lip edge blurred, upper lip hypopigmentation, hypertrichosis, erythema, and pigmentation unilateral: facial alterations were also described in a few cases, among those found. For a 3-year presents clinical, histological and radiological features described for this disease is reported and early treatment of this rare condition.

Hypertrichosis lanuginosa acquisita in a patient with stage 4 non–small cell lung cancer: A case report

Hypertrichosis lanuginosa acquisita in a patient with stage 4 non–small cell lung cancer: A case report

Hypertrichosis lanuginosa acquisita associated with non-Hodgkin lymphoma

Hypertrichosis lanuginosa acquisita associated with non-Hodgkin lymphoma

Genetic Variations: Heroes or Villains

Gene pool of every organism has shown a wide occurrence of genetic variations. Variations have not only been associated with diseases like cancer, turner syndrome, sickle cell anaemia, cystic fibrosis etc., but some of them have even been proved to be beneficial in certain cases like for increasing bone density, lowering down cholesterol level, and for developing malaria resistance. Genetic variations or switches have also been explored for their significant role in evolution of human species. Monogenic diseases are the inherited disorders caused by the mutations in a single gene. Single Nucleotide Polymorphism, structural variants and genomic rearrangements are considered as some of the forms of genetic mutations. Genetic mutations are the fundamental cause of some monogenic disorders such as Schizophrenia, Alzheimer’s disease, Hutchinson-Gilford Progeria syndrome (HGPS), Proteus syndrome and Congenital generalized hypertrichosis (CGH). However, some variants have even offered protection against a disease like blocking of HIV infection due to mutations in co-receptors needed for entry of infection into the cells. This review aims to provide insights into the role of variants present in the genes associated with the monogenic disorders in order to determine the underlying mechanism of the disease, which might further pave a way for the scientists to discover the therapeutic approaches for dealing with the same.

Hypertrichosis lanuginosa acquisita: a rare dermatological disorder

A 75-year-old woman was brought to the emergency department following a syncopal episode in August, 2007. She had a 6 week history of weight loss, exertional dyspnoe a, and non-productive cough, and a 2 month history of increased hair growth. On examination she had new lanugo hair and eyelash trichomegaly (fi gure), and a deeply furrowed tongue. Work-up showed a mass in the right upper lobe. Histology of a biopsy sample of the mass was consistent with adenocarcinoma of the lung stage 3B. She was given a course of palliative radiotherapy, with minor regression of lanugo hair and some improvement in her dyspnoea and cough. She died of pneumonia 3 years after initial presentation. Hypertrichosis lanuginosa acquisita is a rare dermatological disorder sometimes accompanied by lingual papillary hypertrophy or eyelash trichomegaly. It can be associated with malignancy, most often adenocarcinoma of the lung or colon. It is important that clinicians watch for, ask about, and completely investigate any new hair growth. Doing so can enable earlier detection of a malignancy and potentially improve prognosis.

AB143. Berardinelli-Seip congenital lipodystrophy and its diagnostic implications

Berardinelli-Seip congenital lipodystrophy (BSCLD) (OMIM#269700) is a rare autosomal recessive disorder characterized by marked paucity of adipose tissue, a muscular habitus, insulin resistance, hypertriglyceridemia and hepatic steatosis. It is an anabolic syndrome due to the deficiency of leptin, a lipid modulator, leading to the inappropriate mobilization of fat. Four types of BSCLD have been described based on the site of genetic mutation. Type 2 accounts for an earlier onset, more severe complications and intellectual disability. This is due to the lower leptin levels and the loss of functional seipin in type 2 BSCLD. We report the evolving phenotype of type 2 BSCLD in a boy clinically diagnosed at age 5 months and confirmed by molecular genetic study which revealed a pathogenic mutation in the BSCL2 gene: c.782dupG, p.lle262Hisfs*12homozygous. He is the firstborn of non-consanguineous parents with no significant family history. He has a muscular habitus with a distinct facies, hypertrichosis, absence of subcutaneous fat and hepatomegaly. Investigations revealed hypertriglyceridemia and insulin resistance. A conventional approach to management with dietary fat restriction successfully controlled his biochemical parameters, thus preventing catastrophic complications such as systemic arterial hypertension, heart failure and pancreatitis. Genetic counseling was conferred and prenatal testing recommended for future pregnancies. On follow-up, he had a muscular habitus with hepatomegaly and global developmental delay. Despite early correction of his biochemical parameters, an abdominal ultrasound revealed early onset fatty liver disease and an echocardiogram showed a thickened interventricular septum suggestive of early hypertrophic obstructive cardiomyopathy (HOCM). A fasting serum leptin done was low at 0.8 ng/mL (normal range, 2.0-5.6 ng/mL) confirming leptin deficiency. A leptin analog is now available as an adjunct to mollify the metabolic complications of BSCLD. However, it is yet to be available in developing nations and whether it is able to assuage progressive hepatic cholestasis and HOCM remains a field to venture. This report highlights the importance of early recognition and confirmation by molecular diagnosis to direct appropriate surveillance of complications. This also enables early genetic counseling and prenatal testing for future pregnancies. We describe the evolving phenotype, pertinent investigations and the conventional approach to the management of BSCLD.