Wechsler et al. (2004) reported the first female with this syndrome. She had tibial aplasia, mirror image preaxial polydactyly involving her feet, brachyphalangy, genital hypoplasia, and facial dysmorphism including telecanthus, blepharophimosis, flat nasal bridge with a small nose, and small mouth.
Other causes of this condition include a metabolic disorder called Fabry disease, immune disorders such as celiac disease or Sjogren syndrome, an inflammatory condition called sarcoidosis, and human immunodeficiency virus (HIV) infection.
Sodium channelopathy-related small fiber neuropathy is a rare, genetic, peripheral neuropathy disorder due to gain-of-function mutations in voltage-gated sodium channels present in the small peripheral nerve fibers characterized by neuropathic pain of varying intensity (often beginning in the distal extermities and with a burning quality) associated with autonomic dysfunction (e.g. orthostatic dizziness, palpitations, dry eyes and mouth), abnormal quantitative sensory testing, and reduction in intraepidermal nerve fiber density. Large fiber functions (i.e. normal strength, tendon reflexes, and vibration sense) and nerve conduction studies are typically normal.
A number sign (#) is used with this entry because primary erythermalgia is caused by heterozygous mutation in the SCN9A gene (603415), encoding a voltage-gated sodium channel, on chromosome 2q24. Small fiber neuropathy can also be caused by heterozygous mutation in the SCN9A gene. Description 'Primary erythermalgia' is an autosomal dominant disorder characterized by childhood or adolescent onset of episodic symmetrical red congestion, vasodilatation, and burning pain of the feet and lower legs provoked by exercise, long standing, and exposure to warmth. Relief is obtained with cold (Michiels et al., 2005). The severity of the disorder may progress with age, and symptoms may extend over a larger body area, such as over the ankles and lower legs, and become constant (Mandell et al., 1977). Waxman and Dib-Hajj (2005) provided a review of primary erythermalgia.
Primary erythermalgia is characterized by intermittent attacks of red, warm, painful burning extremities. It spontaneously arises during early childhood and adolescence in the absence of any detectable underlying disorder. Epidemiology It may occur sporadically or as an inherited disease, but less than 30 kindreds with familial primary erythermalgia have been reported in the literature so far. Clinical description Clinically, it is characterized by episodes of symmetrical red congestion, vasodilatation, and burning pain in both the feet and lower legs provoked by exercise, long standing and exposure to warmth that usually compels patients not to wear socks or closed shoes even in winter and to search for relief by immersion of feet in ice-cold water. Etiology The gene for autosomal dominant erythermalgia, SCN9a , is located on chromosome 2q.
Erythromelalgia is a condition characterized by episodes of pain, redness, and swelling in various parts of the body, particularly the hands and feet. These episodes are usually triggered by increased body temperature, which may be caused by exercise or entering a warm room. Ingesting alcohol or spicy foods may also trigger an episode. Wearing warm socks, tight shoes, or gloves can cause a pain episode so debilitating that it can impede everyday activities such as wearing shoes and walking. Pain episodes can prevent an affected person from going to school or work regularly. The signs and symptoms of erythromelalgia typically begin in childhood, although mildly affected individuals may have their first pain episode later in life.
Erythromelalgia (EM) is a rare condition characterized by episodes of burning pain, warmth, swelling and redness in parts of the body, particularly the hands and feet. This condition may occur spontaneously (primary EM) or secondary to neurological diseases , autoimmune diseases, or myeloproliferative disorders (secondary EM). Episodes may be triggered by increased body temperature, alcohol, and eating spicy foods. About 15% of cases are caused by mutations in the SCN9A gene and are inherited in an autosomal dominant manner. Other cases may be caused by unidentified genes or by non-genetic factors.
Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a progressive disorder that primarily affects the brain and spinal cord (central nervous system).
Mucopolysaccharidosis type IIIA (MPS IIIA) is a severe, progressive disorder that affects the central nervous system. In people with MPS IIIA, the body cannot break down a large sugar molecule called heparin sulfate. Signs and symptoms usually begin in early childhood and include severe neurological symptoms such as progressive dementia, aggressive behavior, hyperactivity, seizures, deafness, loss of vision, and an inability to sleep for more than a few hours at a time. MPS IIIA is caused by mutations in the SGSH gene and is inherited in an autosomal recessive manner. There is currently no specific treatment for MPS IIIA; affected people usually do not survive past the second decade of life.
Sialidosis is a lysosomal storage disease, belonging to the group of oligosaccharidoses or glycoproteinoses, with a wide clinical spectrum that is divided into two main clinical subtypes: sialidosis type I (see this term), the milder, non dysmorphic form of the disease characterized by gait abnormalities, progressive visual loss, bilateral macular cherry red spots and myoclonus, that presents in adolescence or adulthood (second or third decade of life); and sialidosis type II (see this term) the more severe, early onset form, characterized by a progressive and severe mucopolysaccharidosis-like phenotype with coarse facies, visceromegaly, dysostosis multiplex, and developmental delay. Bilateral macular cherry red spots are also present. Sialidosis type II has been further divided into congenital (with hydrops fetalis), infantile and juvenile presentations.
Sialidosis is a severe inherited disorder that affects many organs and tissues, including the nervous system. This disorder is divided into two types, which are distinguished by the age at which symptoms appear and the severity of features. Sialidosis type I is the less severe form of this condition. People with this condition typically develop signs and symptoms of sialidosis in their teens or twenties. Characteristic features may include sudden involuntary muscle contractions ( myoclonus ), distinctive red spots (cherry-red macules) in the eyes, and sometimes additional neurological findings. Sialidosis type I is caused by mutations in the NEU1 gene. Individuals with sialidosis type I have mutations that result in some functional NEU1 enzyme.
From age 10 years, she developed bone marrow abnormalities, including cytopenia, reduced hematopoiesis, and mild dysplastic features, such as dysmyelopoiesis, dysmegakaryopoiesis, and megaloblastoid erythropoiesis. Myelodysplastic syndrome was excluded on several occasions.
All affected women showing skewed X inactivation inherited the active X chromosome of their fathers. One of the woman had Lowe syndrome (309000) caused by a mutation in the OCRL1 (300535) gene in the paternally transmitted X chromosome.
These reports demonstrate a particularly tight pan-ethnic association between phenotype and genotype in this variant form of Gaucher syndrome. George et al. (2001) identified homozygosity for the D409H mutation in a 17-year-old Palestinian patient with Gaucher disease and cardiovascular calcifications.
Problems noted later included strabismus, easy bruising, poor coordination, and some dysmorphic features. A diagnosis of Prader-Willi syndrome (PWS; 176270) was confirmed by demonstration of an interstitial deletion of 15q11-q13.
Glutathionuria Other names Gamma-glutamyl transpeptidase deficiency [1] Glutathione Glutathionuria is the presence of glutathione in the urine, and is a rare inborn error of metabolism . [2] The condition has been identified in five patients. [3] References [ edit ] ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Gamma glutamyl transpeptidase deficiency" . www.orpha.net . Retrieved 14 April 2019 . ^ Schulman JD, Goodman SI, Mace JW, Patrick AD, Tietze F, Butler EJ (July 1975). "Glutathionuria: inborn error of metabolism due to tissue deficiency of gamma-glutamyl transpeptidase". Biochem. Biophys. Res. Commun . 65 (1): 68–74. doi : 10.1016/S0006-291X(75)80062-3 .
A disorder that is characterized by increased glutathione concentration in the plasma and urine. Epidemiology Gamma-glutamyl transpeptidase deficiency has been detected in seven patients in five families worldwide. Clinical description Five of the patients also had central nervous system involvement. Etiology Gamma-glutamyl transpeptidase catalyses the first step in the degradation of glutathione. No mutations have been identified in patients with gamma-glutamyl transpeptidase deficiency.
A rare benign soft tissue tumor characterized by the development of nodules in the skin, striated muscles, bones, and in exceptional cases, visceral organs, leading to a broad spectrum of clinical symptoms. It contains myofibroblasts. Epidemiology The estimated prevalence is 1/150,000 live births. Clinical description Infantile myofibromatosis (IM) presents at birth or develops shortly thereafter, with 90% of cases occurring before the age of 2 years. IM is characterized by solitary or multiple nodules that are firm, flesh-colored to purple (''myofibroma''), and usually painless (except in case of compression of adjacent nerves). Tumors are located in the skin, subcutaneous tissue, striated muscles and in exceptional cases, visceral organs or bones.
A number sign (#) is used with this entry because infantile myofibromatosis-1 (IMF1) is caused by heterozygous mutation in the PDGFRB gene (173410) on chromosome 5q32. Description Infantile myofibromatosis is a rare mesenchymal disorder characterized by the onset of nodules in the skin, striated muscles, bones, and, more rarely, visceral organs. Subcutaneous or soft tissue nodules commonly involve the skin of the head, neck, and trunk. Skeletal and muscular lesions occur in about 50% of patients. Lesions may be solitary or multicentric, and they may be present at birth or become apparent in early infancy or occasionally in adult life (summary by Arcangeli and Calista, 2006). Genetic Heterogeneity of Infantile Myofibromatosis See also IMF2 (615293), caused by mutation in the NOTCH3 gene (600276).
A number sign (#) is used with this entry because of evidence that infantile myofibromatosis-2 (IMF2) is caused by heterozygous mutation in the NOTCH3 gene (600276) on chromosome 19p13. One such family has been reported. Description Infantile myofibromatosis is a disorder of mesenchymal proliferation characterized by the development of benign tumors in the skin, muscle, bone, and viscera. Soft tissue lesions may regress spontaneously. Visceral lesions are associated with high morbidity and mortality (summary by Martignetti et al., 2013). For a discussion of genetic heterogeneity of infantile myofibromatosis, see IMF1 (228550). Clinical Features Martignetti et al. (2013) reported a 2-generation family (IM-9) in which 9 individuals had infantile myofibromatosis.
A carrier of an unmethylated CGG repeat expansion showed increased levels of DIP2B mRNA, which suggested that the repeat elongation increases gene expression, as previously described for the fragile X-associated tremor/ataxia syndrome (300623). The data suggested that deficiency of DIP2B, a brain-expressed gene, may mediate the neurocognitive problems associated with FRA12A.
Della Marca et al. (2009) reported 7 patients with severe myalgia in the lower limbs and hyperCKemia who were found to have severe restless legs syndrome with severe periodic limb movements in sleep (RLS; 102300).
Isolated hyperCKemia is a condition characterized by elevated levels of an enzyme called creatine kinase in the blood. In affected individuals, levels of this enzyme are typically 3 to 10 times higher than normal. While elevated creatine kinase often accompanies various muscle diseases, individuals with isolated hyperCKemia have no muscle weakness or other symptoms. Some people with this condition have abnormalities of muscle cells that can be seen with a microscope, such as unusual variability in the size of muscle fibers, but these changes do not affect the function of the muscle. Frequency The prevalence of isolated hyperCKemia is unknown. Because the condition has no symptoms, it is likely that some cases never come to medical attention.
A familial nonhypertrophic restrictive cardiomyopathy with autosomal dominant inheritance and incomplete penetrance was described by Cooke et al. (1994) in association with Noonan syndrome (163950). Chen et al. (2001) reviewed the clinical spectrum of restrictive cardiomyopathy in 14 children, 7 of whom had familial cardiomyopathy.
A rare genetic cardiac disease characterized by restrictive ventricular filling due to high ventricular stiffness that results in severe diastolic dysfunction in the absence of dilated or hypertrophied ventricles. Epidemiology The prevalence is unknown; however, from a European registry the familial form is reported to account for 30% of restrictive cardiomyopathy. Clinical description Clinical presentation of restrictive cardiomyopathy (RCM) is heterogeneous, with onset at any age. Dyspnea is the most common symptom, followed by edema, palpitation, fatigue, orthopnea and chest pain. The typical symptoms upon examination include jugular venous distension, elevated systemic and pulmonary venous pressures, systolic murmur, lower-extremity edema, atrial fibrillation, cardiomegaly, and less frequently atrioventricular block.
Familial restrictive cardiomyopathy is a genetic form of heart disease. For the heart to beat normally, the heart (cardiac) muscle must contract and relax in a coordinated way. Oxygen-rich blood from the lungs travels first through the upper chambers of the heart (the atria), and then to the lower chambers of the heart (the ventricles). In people with familial restrictive cardiomyopathy, the heart muscle is stiff and cannot fully relax after each contraction. Impaired muscle relaxation causes blood to back up in the atria and lungs, which reduces the amount of blood in the ventricles.
Large VSDs that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death (summary by Wang et al. (2011, 2011)).
Differential diagnosis Differential diagnosis includes Autoimmune PAP, PAP related to the production of surfactant (e.g. due to mutations in SP-B or SP-C , ABCA3 , and NKX2-1), PAP secondary to hematologic disorders and malignancies, toxic dust inhalations, and immune deficiency syndromes, rare infections, mutations affecting functions or numbers of mononuclear phagocytes, and mutations affecting lung development.
A number sign (#) is used with this entry because of evidence that pulmonary surfactant metabolism dysfunction-5 (SMDP5) is caused by homozygous mutation in the CSF2RB gene (138981) on chromosome 22q12. Description Pulmonary surfactant metabolism dysfunction-5 (SMDP5) is an autosomal recessive lung disorder manifest clinically and pathologically as pulmonary alveolar proteinosis (PAP). PAP is a rare lung disease characterized by the ineffective clearance of surfactant by alveolar macrophages. This results in the accumulation of surfactant-derived lipoproteinaceous material in the alveoli and terminal bronchioles, causing respiratory failure (summary by Greenhill and Kotton, 2009). For a general phenotypic description and a discussion of genetic heterogeneity of pulmonary surfactant metabolism dysfunction, see SMDP1 (265120).
Clinical Features Martinez-Moczygemba et al. (2008) reported a 4-year-old female with symptoms associated with Turner syndrome and respiratory insufficiency who had been diagnosed with PAP at age 3 years.
Congenital pulmonary alveolar proteinosis is a rare form of respiratory failure that is present from birth. In this condition, a substance made up of fat and protein (surfactant) builds up in the air sacs (alveoli) of the lungs, making breathing difficult. Symptoms typically begin the newborn period and get worse over time. Congenital pulmonary alveolar proteinosis is caused by genetic changes (mutations) in one of several different genes. It is inherited in either an autosomal dominant, autosomal recessive or X-linked recessive pattern depending on the gene involved. If the gene involved is the ABCA3 gene, the CSF2RB gene, or the SFTPB gene, inheritance is autosomal recessive.
Differential diagnosis Differential diagnosis includes many other causes of severe hypospadias like partial androgen insensitivity syndrome, 17-beta-hydroxysteroid dehydrogenase 3 deficiency and Leydig cell hypoplasia.
5-alpha reductase deficiency is a condition that affects male sexual development before birth and during puberty. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes) . Their bodies, however, do not produce enough of a hormone called dihydrotestosterone (DHT). DHT has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth. Many people with 5-alpha reductase deficiency are born with external genitalia that appear female.
5-alpha reductase deficiency is an inherited condition that primarily affects male sexual development before birth and during puberty. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of a hormone called dihydrotestosterone (DHT), which is critical for male sexual development. Most are born with external genitalia that appear female. In other cases, affected individuals may have ambiguous genitalia . Others may have genitalia that appear predominantly male, often with an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias).
., Roar Softly and Carry a Great Lipstick (2004) p. 6 ^ Reevy, p. 217 v t e Narcissism Types Collective Egomania Flying monkeys Healthy Malignant Narcissistic personality disorder Spiritual Workplace Characteristics Betrayal Boasting Egocentrism Egotism Empathy (lack of) Envy Entitlement (exaggerated sense of) Fantasy Grandiosity Hubris Magical thinking Manipulative Narcissistic abuse Narcissistic elation Narcissistic rage and narcissistic injury Narcissistic mortification Narcissistic supply Narcissistic withdrawal Perfectionism Self-esteem Self-righteousness Shamelessness Superficial charm Superiority complex True self and false self Vanity Defences Denial Idealization and devaluation Distortion Projection Splitting Cultural phenomena Control freak Don Juanism Dorian Gray syndrome My way or the highway Selfie Related articles Codependency Counterdependency Dark triad Ego ideal "Egomania" (film) Egotheism Empire-building God complex History of narcissism Messiah complex Micromanagement Narcissism of small differences Narcissistic leadership Narcissistic parent Narcissistic Personality Inventory Narcissus (mythology) On Narcissism Sam Vaknin Self-love Self-serving bias Spoiled child The Culture of Narcissism Workplace bullying
Although the term "acute lipoid pneumonia " has been used to refer to the "fire-eater's lung" syndrome, this is a misnomer. [1] Symptoms [ edit ] Oral ingestion of hydrocarbons often is associated with symptoms of mucous membrane irritation, vomiting, and central nervous system depression.