Disease relevance of Acanthosis Nigricans

• We now report the unexpected observation of a FGFR3 transmembrane domain mutation, Ala391Glu, in three unrelated families with Crouzon syndrome and acanthosis nigricans, a specific skin disorder of hyperkeratosis and hyperpigmentation [1].
• Other clinical and biological features include acanthosis nigricans, hyperandrogenism, muscular hypertrophy, hepatomegaly, altered glucose tolerance or diabetes mellitus, and hypertriglyceridemia [2].
• The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: the achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans [3].
• Hirsutism, polycystic ovaries, and elevated levels of plasma testosterone are characteristic clinical features in women with extreme insulin resistance and acanthosis nigricans [4].
• States of hyperinsulinemia with resistance to insulin action on glucose disposal are frequently associated with proliferative tissue abnormalities of the skin (acanthosis nigricans), ovary, and heart [5].

High impact information on Acanthosis Nigricans

• In Crouzon syndrome patients with acanthosis nigricans, a recurrent mutation occurs in the transmembrane domain of FGFR3 [6].
• Beare-Stevenson cutis gyrata syndrome (MIM 123790) is an autosomal dominant condition characterized by the furrowed skin disorder of cutis gyrata, acanthosis nigricans, craniosynostosis, craniofacial dysmorphism, digital anomalies, umbilical and anogenital abnormalities and early death [6].
• Detection of an alteration in the insulin-receptor gene in a patient with insulin resistance, acanthosis nigricans, and the polycystic ovary syndrome (type A insulin resistance) [7].
• As previously seen with antibodies against the insulin receptor from patients with the type B syndrome of insulin resistance and acanthosis nigricans, RAR acutely mimicked the action of insulin by stimulating deoxyglucose uptake [8].
• Two particularly severe dwarfisms, thanatophoric dysplasia type II (TDII) and severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), are associated with glutamic acid (E) and methionine (M) substitutions at the K650 residue in the kinase domain [9].

Chemical compound and disease context of Acanthosis Nigricans

• Dehydroepiandrosterone sulfate (DHEA-S) levels, however, uniformly and progressively decreased by 39% after 12 h of insulin infusion in the normal women and by 31% at 14 h in the woman with hyperandrogenism, insulin resistance, and acanthosis nigricans [10].
• Bimodal correlation between the circulating insulin level and the production rate of dehydroepiandrosterone: positive correlation in controls and negative correlation in the polycystic ovary syndrome with acanthosis nigricans [11].
• Resolution of nicotinic acid-induced acanthosis nigricans by substitution of an analogue (acipimox) in a patient with type V hyperlipidaemia [12].
• The hyperandrogenic-insulin-resistant acanthosis nigricans syndrome affects between 2% and 5% of hirsute women and is characterized by INS resistance, elevated INS levels, acanthosis nigricans, and androgen excess [13].
• The proband's daughter had severe acne, hirsutism, acanthosis nigricans, polycystic ovaries, raised triglyceride, glucose and testosterone level short metacarpals and normal insulin receptor gene [14].

Biological context of Acanthosis Nigricans

• We refer to the phenotype caused by the Lys650Met mutation as "severe achondroplasia with developmental delay and acanthosis nigricans" (SADDAN) because it differs significantly from the phenotypes of other known FGFR3 mutations [15].
• The incidence of acanthosis nigricans (AN), hirsutism, and ovulation in response to clomiphene citrate (CC) was compared between the 2 groups, along with serum levels of gonadotropins, and sex steroids [16].
• However, a specific point mutation in the FGFR3 gene has also been shown to result in Crouzon syndrome associated with acanthosis nigricans [17].
• A case is described of a 58 year old Caucasian male with primary biliary cirrhosis (PBC) who first presented with acanthosis nigricans of both axillae, skin pigmentation, which was pronounced over the posterior surface of the neck, and generalized pruritus [18].
• Height, weight and sitting blood pressure were recorded in 122 patients with acanthosis nigricans, and blood samples were obtained for measuring fasting cholesterol, high-density lipoprotein cholesterol, triglyceride and uric acid levels [19].

Anatomical context of Acanthosis Nigricans

• Fibroblast growth factor receptor 3 (FGFR3) transmembrane mutation in Crouzon syndrome with acanthosis nigricans [1].
• In this study, major steps in the insulin action cascade, receptor binding, kinase activity, and glucose transport activity were evaluated in isolated adipocytes prepared from PCO subjects (n = 8) without acanthosis nigricans and in a group of age and weight-matched controls [normal cycling (NC) n = 8] [20].
• The physical features most often associated with this condition include hypertrichosis, pachyderma, acanthosis nigricans, prominent genitalia, and elfin-like facial characteristics of prominent eyes, wide nostrils, thick lips, and large, low-set ears [21].

Gene context of Acanthosis Nigricans

• Bilateral basilar venous atresia is most common in patients with the FGFR3 ala391glu mutation and crouzonoid features with acanthosis nigricans, but may be found in patients with FGFR2 mutations [22].
• Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al [23].
• Although acanthosis nigricans, a benign skin tumor, has been found in some syndromes associated with germinal activating mutations of FGFR3, the role of activated FGFR3 in the epidermis has never been investigated [24].
• Individuals in Class IV have additional problems related to their weight, including cardiomyopathy, Pickwickian/sleep apnea syndrome, pituitary/gonadal dysfunction, acanthosis nigricans, and significant osteoarthritis [25].
• Costello syndrome is characterised by postnatal growth deficiency, coarse facies, redundant skin on the neck, palms, soles, and fingers, dark skin, acanthosis nigricans, and papillomata [26].

Analytical, diagnostic and therapeutic context of Acanthosis Nigricans

• Patients with an abnormal fasting glucose or with additional risk factors (positive family history of type 2 diabetes, acanthosis nigricans, hyperlipidemia; n=102) underwent an oral glucose tolerance test (OGTT; 1.75 g glucose/kg body weight) [27].
• Pregnancy after treatment with the insulin-sensitizing agent troglitazone in an obese woman with the hyperandrogenic, insulin-resistant acanthosis nigricans syndrome [28].
• A boy affected by severe obesity (kg 117, Body Mass Index 37 kg/m2) and acanthosis nigricans, was treated with octreotide for 150 days (50 micrograms x three daily subcutaneous administrations) [29].
• It is believed that this is the first reported case of acanthosis nigricans occurring in association with PBC, a phenomenon that resolved after liver transplantation [18].
• The aim of this retrospective study was to assess whether acanthosis nigricans is a predictive factor for abnormal glucose tolerance (AGT) in Asian women with polycystic ovary syndrome (PCOS) [30].

References