Chanarin-Dorfman syndrome is a condition in which fats (lipids) are stored abnormally in the body. Affected individuals cannot break down certain fats called triglycerides, and these fats accumulate in organs and tissues, including skin, liver, muscles, intestine, eyes, and ears. People with this condition also have dry, scaly skin (ichthyosis), which is usually present at birth. Additional features of this condition include an enlarged liver (hepatomegaly), clouding of the lens of the eyes (cataracts ), difficulty with coordinating movements (ataxia), hearing loss, short stature, muscle weakness (myopathy), involuntary movement of the eyes (nystagmus), and mild intellectual disability. The signs and symptoms vary greatly among individuals with Chanarin-Dorfman syndrome.

Neutral lipid storage disease (NLSD) refers to a group of diseases characterized by a deficit in the degradation of cytoplasmic triglycerides and their accumulation in cytoplasmic lipid vacuoles in most tissues of the body. The group is heterogeneous: currently cases of NLSD with icthyosis (NLSDI/Dorfman-Chanarin disease; see this term) and NLSD with myopathy (NLSDM/neutral lipid storage myopathy; see this term) can be distinguished. Epidemiology The group of diseases is very rare and the prevalence is unknown (around 50 cases have been reported in medical literature, of which 3 had NLSDM) because of the vagueness of the descriptions. Clinical description In NLSDI, generalized ichthyosis occurs in 95% of cases, moderate myopathic syndrome (or abnormal serum muscle enzyme levels), intellectual deficit and moderate hepatomegaly (or functional impairment of the liver) occur in 60% of cases, ocular (cataract, retinopathy) and hearing abnormalities (deafness) occur in 40% of cases, and neuropathy and short stature occur in 20% of cases. Etiology NLSDI/Dorfman-Chanarin disease is caused by mutations in the ABHD5 gene (3p21), NLSDM by mutations in the PNPLA2/ATGL gene (localized to 11p15.5).

It has been associated genetically with mutations in the CGI58 gene, (for NLSD-I), or the ATGL gene (for NLSD-M.) [1] [2] [3] Contents 1 Cause 1.1 Genetics 2 Pathophysiology 3 Diagnosis 4 Treatment 5 Epidemiology 6 History 7 See also 8 References 9 External links Cause [ edit ] Neutral lipid storage disease is caused by the abnormal and excessive accumulation of lipids in certain bodily tissues, including the liver, the heart, and muscle. [4] Normally, these lipids are stored as lipid droplets and are normally used for metabolism, cell signaling and trafficking of vesicles. [5] Neutral lipid storage disease is a disease that is diagnosed with the simultaneous occurrence of myopathy and/or ichthyosis. ... Excessive accumulation of lipids in tissues not designed for long term storage may underlie the clinical manifestations of weakened skeletal and cardiac muscle, fatty liver, pancreatitis, hypothyroidism, and type 2 diabetes. [ citation needed ] Diagnosis [ edit ] Main physical signs include a fatty liver, a weakened and enlarged heart (cardiomyopathy), inflammation of the pancreas (pancreatitis), reduced thyroid activity (hypothyroidism), type 2 diabetes, abnormal levels of creatine kinase in blood, and increased weakness of proximal muscles due to fatty replacement of skeletal muscle fibers. ... Because there is an increase of fat storage and a decrease in fat catabolism, low fat diets are recommended for slowing the progression of the disease, including the onset of type 2 diabetes and hypothyroidism . In addition, diets containing triglycerides composed of short chain fatty acids are more beneficial than TGAs containing long chain fatty acids. ... Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function. Cells. Feb 2019; 8(2): 187. ^ Laforêt, Pascal, and Christine Vianey-Saban. ... Neutral Lipid Storage Diseases as Cellular Model to Study Lipid Droplet Function. Cells. Feb 2019; 8(2): 187 ^ Vasiljevski ER, Summers MA, Little DG, Schindeler A.

A form of neutral lipid storage disease characterized by the accumulation of lipid vacuoles in leukocytes (so-called Jordan's anomaly seen in peripheral blood smears) and a variety of other cell types. The clinical picture consists of congenital ichthyosis of the congenital ichthyosiform erythroderma type together with variable multisystem involvement. Manifestations include hepatosplenomegaly, myopathy, intestinal disease, growth retardation, cataracts, sensorineural hearing loss, and intellectual disability, among others.

Jordans (1953) found fat-containing cytoplasmic vacuoles in the leukocytes of 2 brothers with progressive muscular dystrophy. ... Rozenszajn et al. (1966) found cytoplasmic vacuoles in 2 sisters with ichthyosis. A follow-up of these sisters (Dorfman et al., 1974) added 2 new cases and pointed out the systemic nature of storage of triglyceride. ... All 3 children likewise had cataracts and mild neurologic deficit involving cranial nerves in particular and at least 2 showed psychomotor delay. Musumeci et al. (1988) described a case in a Sicilian family. ... Huigen et al. (2015) presented a clinical description of 2 patients with congenital ichthyosis.

Chanarin-Dorfman syndrome is an inherited condition in which fats are stored abnormally in the body. Affected individuals cannot break down certain fats called triglycerides . These fats accumulate in organs and tissues, including skin, liver, muscles, intestine, eyes, and ears. At birth, affected individuals usually present with dry, scaly skin. Additional features include an enlarged liver, cataracts, difficulty with coordinating movements (ataxia), hearing loss, short stature, muscle weakness, nystagmus, and mild intellectual disability. The signs and symptoms vary greatly among individuals with this condition.

Specialty Pediatrics , dermatology Porokeratosis is a specific disorder of keratinization that is characterized histologically by the presence of a cornoid lamella, a thin column of closely stacked, parakeratotic cells extending through the stratum corneum with a thin or absent granular layer. [1] : 532 Contents 1 Types 2 Genetics 3 Diagnosis 3.1 Pathology 4 Treatment 5 See also 6 References 7 External links Types [ edit ] Porokeratosis may be divided into the following clinical types: [1] : 532 Plaque-type porokeratosis (also known as "Classic porokeratosis" and "Porokeratosis of Mibelli" [2] ) is characterized by skin lesions that start as small, brownish papules that slowly enlarge to form irregular, annular, hyperkeratotic or verrucous plaques. [1] : 533 [3] : 566 Sometimes they may show gross overgrowth and even horn-like structures may develop. [4] Skin malignancy, although rare, is reported from all types of porokeratosis. ... This was the first report mentioning mucosal malignancy in any form of porokeratosis. [4] Disseminated superficial porokeratosis is a more generalized processes and involves mainly the extremities in a bilateral, symmetric fashion. [1] : 533 In about 50% of cases, skin lesions only develop in sun-exposed areas, and this is referred to as disseminated superficial actinic porokeratosis [1] : 533 Porokeratosis palmaris et plantaris disseminata is characterized by skin lesions that are superficial, small, relatively uniform, and demarcated by a distinct peripheral ridge of no more than 1mm in height. [1] : 534 [2] : 1668 [3] : 567 Linear porokeratosis is characterized clinically skin lesions are identical to those of classic porokeratosis, including lichenoid papules, annular lesions, hyperkeratotic plaques with central atrophy, and the characteristic peripheral ridge. [1] [2] : 1668 [3] : 567 Punctate porokeratosis is a skin condition associated with either classic porokeratosis or linear porokeratosis types of porokeratosis, and is characterized by multiple, minute, and discrete punctate, hyperkeratotic, seed-like skin lesions surrounded by a thin, raised margin on the palms and soles. [1] : 535 [2] : 1668 Porokeratosis plantaris discreta is a skin condition that occurs in adults, with a 4:1 female preponderance, characterized by a sharply marginated, rubbery, wide-based papules. [3] : 213 It is also known as "Steinberg's lesion". [5] It was characterized in 1970. [6] Genetics [ edit ] Linear porokeratosis has been associated with mutations in the PMVK and MVD genes. [7] The PMVK gene encodes the enzyme phosphomevalonate kinase and the MVD gene encodes the enzyme diphosphomevalonate decarboxylase . ... ISBN 0-07-138076-0 . ^ a b c d Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set . St. Louis: Mosby. p. 1668. ... "Porokeratosis plantaris discreta, a previously unrecognized dermatopathological entity". Int. J. Dermatol . 9 (2): 83–90. doi : 10.1111/j.1365-4362.1970.tb04584.x .

The Journal of Clinical Investigation . 121 (2): 613–622. doi : 10.1172/JCI44478 . ... Journal of Cosmetic Dermatology . 15 (2): 120–130. doi : 10.1111/jocd.12198 . ... A Review" . Dermatology and Psychosomatics . 2 (2): 63–71. doi : 10.1159/000049641 . ^ Castle, Sue (2002). ... Archives of Internal Medicine . 160 (2): 165–171. doi : 10.1001/archinte.160.2.165 . ... Skin Pharmacology and Physiology . 7 (1–2): 61–66. doi : 10.1159/000211275 .

Each strand of hair normally grows for 2 to 6 years, goes into a resting phase for several months, and then falls out.

Two (possibly 3) generations of the family were affected with early-onset, mild mucocutaneous candidiasis, increased susceptibility to bacterial infection, hyperkeratosis follicularis, alopecia universalis, keratoconjunctivitis, diarrhea in infancy, T- and B-cell abnormalities, and possibly hypoadrenocorticism. A mother and her 2 daughters were studied in detail. ... Chronic monilial nail infection began in her late teens. The 2 daughters were experiencing a similar evolution of disease. ... Witkop et al. (1982) provided a detailed report of the ocular features in 2 affected members of the family reported by Witkop et al. (1979).

A rare, genetic, immune deficiency with skin involvement characterized by clinical triad of non-scarring alopecia affecting mainly the scalp, well-demarcated mucosal erythema and psoriasiform erythematous intertriginous plaques. Follicular keratosis, keratoconjuctivitis, cataracts, angular cheilitis, fissured tongue, and recurrent infections are additional clinical features. Histopathology of mucosal lesions show characteristic findings of dyskeratotic keratinocytes, vacuolated basal cells, lack of epithelial maturation and decreased number of desmosomes.

Hereditary mucoepithelial dysplasia (HMD) is a very rare condition that affects the skin, hair, mucosa (areas of the body that are lined with mucus), gums (gingiva), eyes, nose and lungs. Symptoms begin in infancy and vary in severity from person to person. The most common symptoms of this condition include hair loss ( alopecia ), patchy red skin around the perineum (the area between the anus and external genitalia); and red gums. Small, skin-colored bumps ( keratosis pilaris ) and early development of cloudy lens (cataracts) are also common. Other symptoms may include eye disease that gets worse over time, lung disease and a rough, red tongue.

Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited disease that affects the brain and muscles. People with this disease may begin showing symptoms from early infancy to age three. Signs and symptoms can vary but may include mild to severe intellectual disability, recurrent seizures (epilepsy), problems with speech, and involuntary movements. People with this disease may also have behavioral problems, including hyperactivity, autistic behaviors , and self-mutilation. GAMT deficiency is caused by changes (mutations) in the GAMT gene. The disease is inherited in an autosomal recessive manner.

The most frequently identified mutation, c.327G>A (p.K109K, splice site exon 2), is present in at least one allele in over 50% of families. c.59G>C is most frequently encountered in Portuguese patients.

A number sign (#) is used with this entry because cerebral creatine deficiency syndrome-2 (CCDS2), also known as guanidinoacetate methyltransferase (GAMT) deficiency, is caused by homozygous or compound heterozygous mutation in the GAMT gene (601240) on chromosome 19p13. ... Four patients were identified with GAMT deficiency: 2 sisters, aged 26 and 29 years, respectively, and their 8-year-old male third cousin, and an isolated case in an unrelated family who was 19 years old at the time of report. ... Verhoeven et al. (2000) reported that creatinine in plasma from 2 GAMT-deficient patients appeared normal when measured by the Jaffe method but was decreased when measured enzymatically or by HPLC. ... Forty-four patients, all treated after 9 months of age, including 2 who had never received treatment, had developmental delay or intellectual disability. ... Stockler-Ipsiroglu et al. (2014) provided consensus recommendations for the diagnosis, treatment, and monitoring of patients with CCDS2. Molecular Genetics In 2 patients with GAMT deficiency, Stockler et al. (1996) identified mutations in the GAMT gene; one patient was homozygous and the other was compound heterozygous (see 601240.0001 and 601240.0002).

Guanidinoacetate methyltransferase deficiency is an inherited disorder that primarily affects the brain and muscles. Without early treatment, people with this disorder have neurological problems that are usually severe. These problems include intellectual disability, speech development limited to a few words, and recurrent seizures (epilepsy). Affected individuals may also exhibit autistic behaviors that affect communication and social interaction or self-injurious behaviors such as head-banging. Other features of this disorder can include involuntary movements (extrapyramidal dysfunction) such as tremors or facial tics.

A clinical variant of iridocorneal endothelial (ICE) syndrome, characterized by very few iris abnormalities but more severe corneal edema and less severe secondary glaucoma than seen in the other two ICE syndrome variants: Cogan-Reese syndrome and essential iris atrophy.

A rare primary bone dysplasia characterized by Perthes-like pelvic anomalies (premature closure of the capital femoral epiphyses and widened femoral necks with flattened femoral heads), arthralgias of hips and knees, and occurrence of enchondromata and ecchondromata. There have been no further descriptions in the literature since 1971.

Upington disease Other names Perthes-like hip disease, Enchondromata, Ecchondromata , and Familial dyschondroplasia , [1] [2] Upington disease has an autosomal dominant pattern of inheritance. ... It has only one published source claiming its existence in three generations of one family from South Africa . [4] Contents 1 Presentation 2 Genetics 3 Management 4 Eponym 5 References 6 External links Presentation [ edit ] The disease is characterized by Perthes-like pelvic anomalies (premature closure of the capital femoral epiphyses and widened femoral necks with flattened femoral heads), enchondromata and ecchondromata . [ citation needed ] Genetics [ edit ] Upington disease is inherited in an autosomal dominant manner. [4] [5] This means the defective gene is located on an autosome , and one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. [ citation needed ] Management [ edit ] This section is empty.

Pineoblastoma is a rare, malignant type of supratentorial primitive neuroectodermal tumor (sPNET), found mainly in children (less than 10% of cases are reported in adults), and located in the pineal region of the brain but that can metastasize along the neuroaxis. As it is the most aggressive of the pineal parenchymal tumors, it is usually associated with a poor prognosis.

Pineoblastoma is a type of cancerous ( malignant ) tumor that grows in a part of the brain known as the pineal gland . It occurs mainly in children. Symptoms of pineoblastoma include a buildup of fluid around the brain (hydrocephalus), headaches, nausea, and difficulty with eye movement. Without treatment, pineoblastomas can cause weakness and difficulty controlling movement. The long term outcome depends on the age at diagnosis, the size of the tumor, and if the tumor has spread outside the brain ( metastasized ). The cause of pineoblastoma is unknown, but specific inherited genetic variants in two genes, RB1 and DICER1 can increase the risk for a pineoblastoma.

Trichoodontoonychial dysplasia is a rare ectodermal dysplasia syndrome characterized by severe generalized hypotrichosis, parietal alopecia, secondary anodontia resulting from enamel hypoplasia, onychodystrophy, bone deficiency in the frontoparietal region and skin manifestations (incl. nevus pigmentosus, papules, ephelides, palmoplantar keratosis, supernumerary nipples, abnormal dermatoglyphics). There have been no further descriptions in the literature since 1983.

(See 226400 and 305350 for possible examples of skin disorders (epidermodysplasia verruciformis) due to genetic susceptibility to HPV.) In 2 of 4 sibs born of Mexican-American parents of Navajo and Comanche Native American lineage, Mealey et al. (1993) described FEH in association with leukocyte adhesion deficiency (116920).

Silent sinus syndrome is characterised by adult-onset progressive enophthalmos due to collapse of some or all of the maxillary sinus walls. Epidemiology Its prevalence is unknown but around 100 cases have been reported in the literature so far. Clinical description The progressive enophthalmos may occasionally be associated with cheek pain, diplopia and blurred vision. Patients sometimes report a history of remote episodes of sinusitis. The syndrome may be idiopathic or occur following a bony orbital decompression resulting from Graves' ophthalmopathy or orbital floor fracture. Etiology The underlying mechanism involves obstruction of the maxillary antrum aeration followed by generation of negative antral pressure.