Sztriha et al. (1999) described 2 infants, born in an inbred Arab family, with a syndrome of micrencephaly with simplified gyral pattern, abnormal myelin formation, and arthrogryposis.
Clinically the disorder shows a slowly progressive glomerular insufficiency rather than the prominent Fanconi syndrome, electrolyte and water disturbances, growth arrest, and rickets typical of infantile cystinosis.
A subtype of cystinosis characterized by an accumulation of cystine in different organs and tissues, particularly in the kidneys and eyes, and that clinically manifests between childhood and adolescence with a slowly progressive proximal tubulopathy and/or proteinuria, and photophobia. Extra-renal manifestations (e.g. hypothyroidism, insulin-dependent diabetes, hepatosplenomegaly, muscular and cerebral involvement) are less severe than in the infantile form of the disease.
Santos-Cortez et al. (2013) noted that there were no other syndromic, vestibular, neurologic, or systemic abnormalities detected on physical examination of affected individuals in the 3 families.
Primary orthostatic tremor (POT), or ``shaky legs syndrome'', is a rare movement disorder characterized by fast, task-specific tremor, affecting the legs and trunk while standing.
Primary orthostatic tremor (POT) is a rare, progressive movement disorder that causes unsteadiness when standing still, due to a rapid tremor affecting the legs and trunk. The tremor is sometimes described as having “shaky legs,” and it improves or disappears when walking, sitting, or lying down. This may cause people with POT to attempt to sit again or walk immediately after standing, for fear of falling. People with POT may also experience tiredness, physical exhaustion, muscle stiffness or weakness, and/or pain. Symptoms tend to gradually worsen over time and may lead to the need for a mobility aid such as a cane, scooter, or wheelchair.
Differential diagnosis The differential diagnosis should include glomuvenous malformations (GVMs, which are deeper purple in color than VMCMs, painful on palpation, and more superficial than venous malformations; see this term) and Blue rubber bleb nevus syndrome (characterized by the association of cutaneous and mucosal venous-like lesions with gastrointestinal lesions; see this term).
Gallione et al. (1995) noted that the disorder in this family was similar to the blue rubber bleb nevus syndrome (112200), pointing out that the family originally described by Bean (1958), like their family, had gastrointestinal bleeding from vascular lesions. Gallione et al. (1995) suggested that blue rubber bleb nevus syndrome might be a subset in the general category of familial venous malformations.
Multiple cutaneous and mucosal venous malformations (also known as VMCM) are bluish patches (lesions) on the skin (cutaneous) and the mucous membranes, such as the lining of the mouth and nose. These lesions represent areas where the underlying veins and other blood vessels did not develop properly (venous malformations). The lesions can be painful, especially when they extend from the skin into the muscles and joints, or when a calcium deposit forms within the lesion causing inflammation and swelling. Most people with VMCM are born with at least one venous malformation. As affected individuals age, the lesions present from birth usually become larger and new lesions often appear.
Summary Clinical characteristics. The condition multiple cutaneous and mucosal venous malformations (VMCM) is characterized by the presence of small, multifocal bluish cutaneous and/or mucosal venous malformations. They are usually present at birth. New lesions appear with time. Small lesions are usually asymptomatic; larger lesions can invade subcutaneous muscle and cause pain. Malignant transformation has not been reported. Diagnosis/testing. The diagnosis of VMCM is established in a proband with small, multifocal cutaneous and/or mucosal bluish-purple vascular malformations with slow blood flow on Doppler ultrasound AND/OR by the identification of a heterozygous gain-of-abnormal-function pathogenic variant in TEK by molecular genetic testing. Management. Treatment of manifestations: Sclerotherapy, alone or in combination with plastic and reconstructive surgery, is used depending on the size and location of the lesions. Low molecular-weight heparin (LMWH) should be administered prior to any invasive procedure.
Molecular Genetics Najmabadi et al. (2011) performed homozygosity mapping followed by exon enrichment and next-generation sequencing in 136 consanguineous families (over 90% Iranian and less than 10% Turkish or Arabic) segregating syndromic or nonsyndromic forms of autosomal recessive intellectual disability.
SCCB is generally believed to have a high metastatic potential. Rare cases of paraneoplastic syndromes such as ectopic ACTH secretion and hypercalcemia have also been reported.
Differential diagnosis The differential diagnosis may also include Guillain-Barré syndrome, transverse myelitis (see these terms), spinal cord compression and hysteria, as well as muscle weakness and fatigue associated with hyperthyroidism in patients with thyrotoxic myopathy or myasthenia gravis (see this term).
A number sign (#) is used with this entry because of evidence that susceptibility to thyrotoxic periodic paralysis-1 (TTPP1) is conferred by variation in the CACNA1S gene on chromosome 1q32. Description Thyrotoxic periodic paralysis is a sporadic muscle disorder characterized by episodic attacks of weakness associated with hypokalemia in individuals with hyperthyroidism. The paralysis resolves upon treatment of hyperthyroidism. The disorder is most common among males of Asian descent, including Chinese, Japanese, Vietnamese, Filipino, and Koreans, although it occurs less commonly in individuals of Caucasian background. Thyrotoxic periodic paralysis is clinically similar to hereditary hypokalemic periodic paralysis (HOKPP; 170400), but the paralysis in TTPP occurs only in the presence of hyperthyroidism. TTPP can also be precipitated by factors that result in hypokalemia, such as carbohydrate ingestion and rest after exercise (review by Kung, 2006).
A number sign (#) is used with this entry of evidence that susceptibility to thyrotoxic periodic paralysis-2 (TTPP2) is conferred by variation in the KCNJ18 gene (613236) on chromosome 17p11. For a general phenotypic description and a discussion of genetic heterogeneity of susceptibility to thyrotoxic periodic paralysis, see 188580. Clinical Features Ryan et al. (2010) evaluated patients with TTPP, as characterized by episodic flaccid paralysis, hypokalemia during the attacks, and laboratory evidence of thyrotoxicosis. Molecular Genetics Ryan et al. (2010) identified 6 different mutations in the KCNJ18 gene in patients with thyrotoxic periodic paralysis. Four of the mutations (613236.0001-613236.0004) were found to confer susceptibility to the disorder.
For a general phenotypic description and a discussion of genetic heterogeneity of susceptibility to thyrotoxic periodic paralysis, see 188580. Mapping Cheung et al. (2012) conducted a genomewide association study and a replication study with a total of 123 southern Chinese with thyrotoxic periodic paralysis (TTPP) (cases) and 1,170 healthy controls and identified a susceptibility locus on chromosome 17q24.3 near KCNJ2 (600681) (rs312691; odds ratio = 3.3; p metaanalysis = 1.8 x 10(-14)). All subjects with TTPP also had Graves disease (275000), and subsequent TTPP versus Graves disease comparison confirmed that the association at 17q24.3 was specific to TTPP. The area under the curve of rs312691 genotype for risk prediction of TTPP in subjects with Graves disease was 0.73. Expression quantitative trait locus analysis identified SNPs in the region flanking rs312691 (+/- 10 kb) that could potentially affect KCNJ2 expression (p = 0.0001).
Management and treatment Different therapeutic strategies have been reported for the disease, but treatment options are still not defined. The treatment of nephrotic syndrome is based on prednisone, alone in patients with preserved renal function, or associated with cyclophosphamide in cases with crescentic FGN.
Fibrillary glomerulonephritis is an uncommon cause of glomerular disease. A more rare disorder known as immunotactoid glomerulpathy is a very similar condition. Both disorders probably result from deposits derived from immunoglobulins but in most cases the cause is idiopathic (unknown). The diagnosis is made with a kidney biopsy and by electron microscopy . Fibrillary glomerulonephritis and immunotactoid glomerulopathy can be differentiated from each other by electron microscopy; the fibrils in fibrillary glomerulonephritis are smaller and randomly oriented as opposed to the larger and often organized fibrils of immunotactoid glomerulopathy.
This patient developed a severe phenotype reminiscent of Ehlers-Danlos syndrome at the age of 4, with extreme hyperlaxity of the joints leading to immobility and limited mobility as a teenager.
Clinical description Hyperphenylalaninemia is classified by blood Phe concentrations of more than 1,200 micromol/L (classic PKU) or less than 600 micromol/L (mild hyperphenylalaninemia), between 600 and 1,200 micromol/L as mild PKU. Maternal phenylketonuria syndrome has been shown to result in intrauterine and postnatal growth retardation with associated low birth weight, microcephaly, and intellectual disability in the offspring.
Huntley and Stevenson (1969) and Hanley et al. (1987) reviewed the subject of PKU embryofetopathy, also known as the maternal PKU syndrome. Huntley and Stevenson (1969) described 2 sisters with PKU who had a total of 28 pregnancies. ... Superti-Furga et al. (1991) reported the maternal PKU syndrome in cousins, caused by mild unrecognized PKU in their mothers, who were homozygous for the arg261-to-gln mutation (612349.0006). ... Coarctation of the aorta and hypoplastic left heart syndrome were overrepresented. Other Features Brumm et al. (2010) reviewed studies of psychiatric symptoms and disorders in patients with PKU.
A range of nonhemostatic symptoms are often present, including developmental and skeletal anomalies (stippling of the long bones, shortness of the distal phalanges of the fingers, osteoporosis) and pseudoxanthoma elasticum-like syndrome (see this term). Etiology VKCFD is an autosomal recessive disorder caused by mutations in the genes encoding either gamma-glutamyl carboxylase ( GGCX ; 2p12) or the vitamin K 2,3-epoxide reductase complex subunit 1 ( VKORC1 ; 16p11.2).
A number sign (#) is used with this entry because VKCFD2 is caused by homozygous mutation in the VKORC1 gene (608547), which encodes vitamin K epoxide reductase, on chromosome 16p11. For a general phenotypic description and a discussion of genetic heterogeneity of combined deficiency of vitamin K-dependent clotting factors, see VKCFD1 (277450). Description Deficiency of all vitamin K-dependent clotting factors leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. Familial multiple coagulation factor deficiency is rare. Clinical symptoms of the disease include episodes of intracranial hemorrhage in the first weeks of life, sometimes leading to a fatal outcome (Fregin et al., 2002). Clinical Features Oldenburg et al. (2000) described 2 pedigrees showing an autosomal recessive transmission of familial multiple coagulation factor deficiency.
The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. ... Cervical vertebral anomalies are a relatively common finding in warfarin embryopathy and in the related Binder syndrome (155050). Molecular Genetics In an editorial on variants of vitamin K-dependent coagulation factors, Bertina et al. (1979) stated that 9 defective variants of factor II, 5 variants of factor X, and many variants (about 180 pedigrees) of factor IX had been identified.
Differential diagnosis Differential diagnosis of PACNS is extensive and challenging, and comprises a range of systemic inflammatory conditions, infections, conditions with cerebral angiographic abnormalities (in particular, reversible vasoconstriction syndrome (RCVS) has highly similar clinical presentation; however, the associated headache is predominantly thunderclap by quality), and other neoplastic, genetic or neurological conditions.
Primary angiitis of the central nervous system is a rare form of vasculitis (inflammation of blood vessels) affecting the blood vessels that nourish the brain, spinal cord and peripheral nerves. This condition can lead to narrowing and blockage of the blood vessels of the central nervous system which can eventually cause aneurysms , ischemia and/or hemmorrhage . The cause of this condition is unknown. Signs and symptoms of this condition may begin suddenly or develop over time. Some of the symptoms may incude headaches that do not go away, fever, rapid weight loss, confusion or forgetfulness, and general malaise. Treatment for this condition involves a course of immunosuppresive steroids .
Certain subtypes may occasionally be associated with isosexual precocity, dysgenetic gonads, virilization, hyperthyroidism or carcinoid syndrome (see this term). Malignant germ cell tumor of ovary comprises the following histological subtypes: malignant dysgerminomatous germ cell tumor (most frequent form), malignant non dysgerminomatous germ cell tumor (yolk sac tumor, embryonal carcinoma, mixed germ cell tumor), primary non-gestational choriocarcinoma of ovary and malignant teratoma of ovary.
Description Ovarian germ cell cancers are malignancies that arise from germ cells of the embryonic gonad. Although benign germ cell tumors are relatively common, accounting for approximately 20% of all ovarian neoplasms, malignant ovarian germ cell tumors are rare. Weiss et al. (1977) estimated that less than 5% of ovarian cancers are of germ cell origin. Inheritance Jackson (1967) reported a Jamaican family in which grandmother, mother, and daughter developed ovarian cancer (167000); 2 tumors were known to have been dysgerminomas. Stettner et al. (1999) found previous reports of 6 families in which more than 1 woman had a malignant germ cell tumor, and presented an additional ovarian germ cell cancer family in which a mother, her daughter, and her niece were affected.
Differential diagnosis Differential diagnosis includes X-linked hypophosphatemia (XLH), autosomal recessive hypophosphatemia (ARHP), hereditary hypophosphatemic rickets with hypercalciuria (HHRH), fibrous dysplasia of bones, renal Fanconi syndrome (see these terms), vitamin D deficiency, and tumor-induced osteomalacia.
X-linked dominant hypophosphatemic rickets This condition is inherited in an autosomal dominant manner Specialty Endocrinology Autosomal dominant hypophosphatemic rickets ( ADHR ) is a rare hereditary disease in which excessive loss of phosphate in the urine leads to poorly formed bones ( rickets ), bone pain , and tooth abscesses . ADHR is caused by a mutation in the fibroblast growth factor 23 (FGF23). ADHR affects men and women equally; symptoms may become apparent at any point from childhood through early adulthood. Blood tests reveal low levels of phosphate ( hypophosphatemia ) and inappropriately normal levels of vitamin D . [ citation needed ] Occasionally, hypophosphatemia may improve over time as urine losses of phosphate partially correct. [ citation needed ] ADHR may be lumped in with X-linked hypophosphatemia under general terms such as hypophosphatemic rickets . Hypophospatemic rickets are associated with at least nine other genetic mutations. [1] Clinical management of hypophospatemic rickets may differ depending on the specific mutations associated with an individual case, but treatments are aimed at raising phosphate levels to promote normal bone formation. [2] References [ edit ] ^ Online Mendelian Inheritance in Man (OMIM): 193100 ^ "Hypophosphatemic rickets" .
Idiopathic acute eosinophilic pneumonia (IAEP) is characterized by the rapid accumulation of eosinophils in the lungs. Eosinophils are a type of white blood cell and are part of the immune system. IAEP can occur at any age but most commonly affects otherwise healthy individuals between 20 and 40 years of age. Signs and symptoms may include fever, cough, fatigue, difficulty breathing (dyspnea), muscle pain, and chest pain. IAEP can progress rapidly to acute respiratory failure . The term “idiopathic” means the exact cause for the overproduction of eosinophils is not known.
Obese family members all fulfilled criteria consistent with metabolic syndrome, including hypertension with systolic blood pressure greater than 140 mm Hg, fatty liver disease by ultrasound, and insulin resistance.
A rare, genetic form of obesity characterized by morbid obesity, hypertension, type 2 diabetes mellitus and dyslipidemia leading to early coronary disease, myocardial infarction and congestive heart failure. Intellectual disability and decreased sperm counts or azoospermia have also been reported.