A rare neurologic disease characterized by bilateral cataract, Dandy-Walker malformation, and childhood onset of distal spinal muscular atrophy. Patients present with progressively deteriorating symmetrical distal muscle weakness and atrophy of the lower limbs (and, to a much lesser degree, also the upper limbs) and decreased tendon reflexes in the lower and upper limbs.
A rare, hereditary, cerebellar ataxia disorder characterized by late-onset spinocerebellar ataxia, manifesting with slowly progressive gait disturbances, dysarthria, limb and truncal ataxia, and smooth-pursuit eye movement disturbance, associated with a history of psychomotor delay from childhood. Mild atrophy of the cerebellar vermis and hemispheres is observed on brain imaging.
A number sign (#) is used with this entry because of evidence that autosomal recessive spinocerebellar ataxia-11 (SCAR11) is caused by homozygous mutation in the SYT14 gene (610949) on chromosome 1q32. One such family has been reported. Clinical Features Doi et al. (2011) reported 2 Japanese brothers, born of consanguineous parents, with spinocerebellar ataxia associated with psychomotor retardation. One patient had mild psychomotor retardation since childhood, graduated from a normal junior high school, and held a job for several years, whereas the other had more severe psychomotor retardation, went to a school for the disabled, and later lived in an assisted facility. Both developed a progressive gait disorder in their fifties, followed by dysarthria, limb ataxia, truncal ataxia, and disturbance of smooth eye movements. One had nystagmus. Neither had involuntary movements. Brain MRI showed mild atrophy of the cerebellar vermis and hemispheres.
A rare genetic parenchymatous liver disease characterized by infantile or early childhood onset of recurrent episodes of acute liver failure precipitated by a febrile illness. During the life-threatening episodes, patients present with vomiting, lethargy, jaundice, as well as elevated levels of liver enzymes and coagulopathy. There is usually complete recovery between the episodes with conservative treatment.
A number sign (#) is used with this entry because of evidence that infantile liver failure syndrome-2 (ILFS2) is caused by homozygous or compound heterozygous mutation in the NBAS gene (608025) on chromosome 2p24. Description Infantile liver failure syndrome-2 is an autosomal recessive disorder characterized by recurrent episodes of acute liver failure during intercurrent febrile illness. ... For a discussion of genetic heterogeneity of infantile liver failure syndrome, see ILFS1 (615438). Clinical Features In 10 unrelated families, most apparently of European descent, Haack et al. (2015) identified 11 patients, aged 3 to 37 years, with onset of recurrent acute liver failure in infancy.
A rare bone disease characterized by spontaneous adult-onset tarsal navicular osteonecrosis. Patients present with chronic mid- and hindfoot pain, swelling and tenderness over the dorsomedial aspect of the midfoot, flattening of the medial longitudinal arch, and pes planovarus. Radiographic findings include comma-shaped deformity due to collapse of the lateral part of the navicular bone and medial or dorsal protrusion of a portion or the entire bone. The condition may be bilateral or asymmetric and associated with pathological fractures.
A rare systemic disease characterized by congenital muscle hypotonia and/or muscle atrophy that improves with age, proximal joint contractures (knee, hip, elbow), and hypermobility of distal joints. Additional features include soft, doughy skin, atrophic scarring, delayed motor development, and myopathic findings in muscle biopsy. Abnormal craniofacial features have been reported in some patients. Molecular testing is obligatory to confirm the diagnosis.
A rare genetic disease characterized by severe pre- and postnatal growth failure with short stature and microcephaly, facial dysmorphism (including a small jaw and prominent midface), severe insulin resistance, fatty liver, and hypertriglyceridemia developing in childhood, and primary gonadal failure. Mild global learning difficulties and acanthosis nigricans have also been reported.
Neilan et al. (2008) diagnosed the patient with Cockayne syndrome (216400). Guo et al. (2015) restudied this patient when she was 23 years of age. Her features, which included short stature, microcephaly, developmental delay, deep-set eyes, and progressive neuronal degeneration including ataxia, resembled those of patients with Cockayne syndrome; however, she had no history of photosensitivity and a relatively slow progression of symptoms. ... Bee et al. (2015) reported 50-year-old Italian monozygotic twin brothers, born to first-cousin parents, who had a progressive neurologic syndrome and dilated cardiomyopathy. Both brothers had short stature with short limbs, hypotelorism, cryptorchidism, and pes cavus. ... De Bruin et al. (2015) studied a brother and sister from rural Chile who exhibited severe short stature, microcephaly, gonadal failure, and early-onset metabolic syndrome. Both sibs were small for gestational age and displayed progressive postnatal growth failure. ... In a brother and sister from rural Chile with short stature, microcephaly, hypergonadotropic hypogonadism, and early-onset metabolic syndrome, de Bruin et al. (2015) sequenced candidate genes and excluded mutation in the IGF1 (147440) signaling pathway or in 3M syndrome (see 273750)-associated genes.
A rare genetic disease characterized by severe progressive sensorineural hearing loss and progressive cerebellar signs including gait ataxia, action tremor, dysmetria, dysdiadochokinesis, dysarthria, and nystagmus. Absence of deep tendon reflexes has also been reported. Age of onset is between infancy and adolescence. Brain imaging may show variable cerebellar atrophy in some patients.
A number sign (#) is used with this entry because of evidence that Lichtenstein-Knorr syndrome (LIKNS) is caused by homozygous mutation in the SLC9A1 gene (107310) on chromosome 1p36. One such family has been reported. Description Lichtenstein-Knorr syndrome is an autosomal recessive neurologic disorder characterized by postnatal onset of severe progressive sensorineural hearing loss and progressive cerebellar ataxia. ... The phenotype was consistent with Lichtenstein-Knorr syndrome. Barbieri et al. (1986) reported a 43-year-old man who developed progressive and complete sensorineural hearing loss at age 25 and progressive cerebellar ataxia at age 30. ... Molecular Genetics In 3 sibs, born of consanguineous Turkish parents, with Lichtenstein-Knorr syndrome, Guissart et al. (2015) identified a homozygous missense mutation in the SLC9A1 gene (G305R; 107310.0001).
A rare genetic eye disease characterized by optic disc anomalies (bilateral colobomatous optic discs, retinal vessels arising from the peripheral optic disc) and macular atrophy. Peripapillary chorioretinal atrophy and chorioretinal and iris coloboma have also been described. Patients present with horizontal nystagmus and poor visual acuity.
A number sign (#) is used with this entry because of evidence that optic disc anomalies with retinal and/or macular dystrophy (ODRMD) is caused by homozygous mutation in the SIX6 gene (606326) on chromosome 14q23. Clinical Features Aldahmesh et al. (2013) reported 2 brothers, born of healthy first-cousin Syrian parents, who had optic nerve dysplasia, retinal dystrophy, and microphthalmia. In addition to small ocular globes, the 5-year-old brother had bilateral dystrophic retinas with small dysplastic optic nerve heads. His 16-month-old brother had buphthalmos and corneal scarring of the right eye that was presumed to be the result of neglected infantile glaucoma; no eye was visible on the left. Ocular ultrasound revealed large optic nerve cupping and retinal detachment in the right eye, whereas the left eye was extremely short and without retinal detachment.
A rare genetic disease characterized by onset of neurological deterioration in the first two years of life, progressing to severe intellectual disability, profound ataxia, mild dyskinesia, axial hypotonia, camptocormia, and oculomotor apraxia. Some patients also develop nephropathy with features of tubulointerstitial nephritis, hypertension, and a tendency for hyperkalemia.
A number sign (#) is used with this entry because of evidence that Birk-Landau-Perez syndrome (BILAPES) is caused by homozygous mutation in the SLC30A9 gene (604604) on chromosome 4p13. ... Molecular Genetics In 6 affected individuals from a highly consanguineous Bedouin kindred from Saudi Arabia with Birk-Landau-Perez syndrome, Perez et al. (2017) identified a homozygous in-frame 3-bp deletion in the SLC30A9 gene (Ala350del; 604604.0001).
A rare developmental defect with connective tissue involvement characterized by joint hyperextensibility and multiple dislocations of large joints, severe myopia, and short stature. Other common features include retinal detachment, iris and chorioretinal coloboma, kyphoscoliosis and other spine deformities, pectus carinatum, talipes equinovarus, and progressive hearing loss.
Patel et al. (2017) considered the phenotype in the 2 families to be consistent with an autosomal recessive form of Larsen syndrome (see 150250), although they observed a number of clinical and radiologic differences between their patients and previously reported patients. The authors stated that the most striking difference was the severe eye phenotype in their patients, noting that eye involvement is unusual in Larsen syndrome. Molecular Genetics By combined autozygome and exome sequencing in 2 consanguineous Saudi families with short stature, joint laxity, and severe myopia, Patel et al. (2017) identified homozygous mutations in the GZF1 gene: a nonsense mutation (E289X; 613842.0001) in one family and a frameshift mutation (613842.0002) in the other.
A rare mitochondrial disease characterized by a variable phenotype comprising congenital sensorineural deafness, intermittent or persistent hypoglycemia, and hepatic and renal dysfunction potentially progressing to organ failure. Serum lactate levels are variably increased, deficiency of mitochondrial respiratory chain complexes I, III, and IV is observed in the liver and in fibroblasts.
A number sign (#) is used with this entry because of evidence that combined oxidative phosphorylation deficiency-34 (COXPD34) is caused by homozygous mutation in the MRPS7 gene (611974) on chromosome 17q25. One such family has been reported. Description COXPD34 is an autosomal recessive disorder resulting from a defect in mitochondrial function. The phenotype is variable, but may include congenital sensorineural deafness, increased serum lactate, and hepatic and renal dysfunction. Neurologic function is relatively preserved (summary by Menezes et al., 2015). For a discussion of genetic heterogeneity of combined oxidative phosphorylation deficiency, see COXPD1 (609060).
Mitochondrial myopathy-lactic acidosis-deafness is a type of metabolic myopathy described only in two sisters to date, presenting during childhood, and characterized clinically by growth failure, severe muscle weakness, and moderate sensorineural deafness and biochemically by metabolic acidosis, elevated serum pyruvate concentration, hyperalaninemia and hyperalaninuria. There have been no further descriptions in the literature since 1973.
A number sign (#) is used with this entry because of evidence that mitochondrial myopathy with lactic acidosis (MMLA) is caused by compound heterozygous mutation in the PNPLA8 gene (612123) on chromosome 7q31. One such family has been reported. Clinical Features Saunders et al. (2015) reported a 7-year-old girl, born of unrelated parents, with a mitochondrial myopathy. She had normal early development, with the exception of toe-walking, but began to show severe progressive proximal muscle weakness resulting in loss of ambulation by age 3 years. Independent sitting became difficult due to fatigue. Her fine motor skills declined, speech became dysarthric, and hypotonicity progressed to spasticity. Other features included complex partial seizures, lactic acidosis, and increased serum pyruvate.
An early-onset distal osteolysis characterised by severe resorption of the hands and feet and absence of the distal and middle phalanges. It has been described in a son and daughter born to consanguineous parents. Other manifestations include distal muscular hypertrophy, flexion contractures, short stature, mild intellectual deficit and characteristic facies (maxillary hypoplasia, exophthalmos, and a broad nasal tip). It is transmitted as an autosomal recessive trait.
Petit and Fryns (1986) described an apparently autosomal recessive form of distal osteolysis in the son and daughter of unaffected consanguineous parents. The hands and feet showed severe resorption abnormalities with absence of the distal and middle phalanges. There was distal muscular hypertrophy, and the skin of the volar part of the hands was loose without other peculiarities. The osteolysis had begun at an early age and was rapidly progressive. Changes were most pronounced in the phalanges but occurred also in the distal ulnar and radial epiphyses.
A rare, primary bone dysplasia characterized by severe growth retardation, short stature, cortical thickening and medullary stenosis of long bones, delayed closure of the anterior fontanelle, absent diploic space in the skull bones, prominent forehead, macrocephaly, dental anomalies, eye problems (hypermetropia and pseudopapilledema), and hypocalcemia due to hypoparathyroidism, sometimes resulting in convulsions. Intelligence is normal.
A tumor that often causes a syndrome of diarrhea and electrolyte imbalance VIPoma Specialty Oncology A VIPoma or vipoma ( / v ɪ ˈ p oʊ m ə / ) is a rare endocrine tumor [1] that overproduces vasoactive intestinal peptide (thus VIP + -oma ). ... Roughly 50%-75% of VIPomas are malignant , but even when they are benign , they are problematic because they tend to cause a specific syndrome : the massive amounts of VIP cause a syndrome of profound and chronic watery diarrhea and resultant dehydration , hypokalemia , achlorhydria , acidosis, flushing and hypotension (from vasodilation ), hypercalcemia , and hyperglycemia . [2] [3] This syndrome is called Verner–Morrison syndrome ( VMS ), WDHA syndrome (from watery diarrhea–hypokalemia–achlorhydria), or pancreatic cholera syndrome ( PCS ). The eponym reflects the physicians who first described the syndrome. [4] Contents 1 Symptoms and signs 2 Diagnosis 3 Treatment 4 Prognosis 5 References 6 External links Symptoms and signs [ edit ] The major clinical features are prolonged watery diarrhea (fasting stool volume > 750 to 1000 mL/day) and symptoms of hypokalemia and dehydration . ... During attacks of diarrhea, flushing similar to the carcinoid syndrome occur rarely. [ citation needed ] Diagnosis [ edit ] Besides the clinical picture, fasting VIP plasma level may confirm the diagnosis, and CT scan and somatostatin receptor scintigraphy are used to localise the tumor , which is usually metastatic at presentation. [ citation needed ] Tests include: Blood chemistry tests (basic or comprehensive metabolic panel) CT scan of the abdomen MRI of the abdomen Stool examination for cause of diarrhea and electrolyte levels Vasoactive intestinal peptide (VIP) level in the blood [ citation needed ] Treatment [ edit ] The first goal of treatment is to correct dehydration. ... Retrieved 2018-04-17 . ^ Verner JV, Morrison AB (Sep 1958). "Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia".
When a person has a VIPoma and these associated symptoms, it is referred to as VIPoma syndrome, also called WDHA syndrome or Verner-Morrison syndrome. The majority of people with a VIPoma have VIPoma syndrome. VIPomas are usually diagnosed in middle-aged adults or in young children.
VIPoma is an extremely rare type of pancreatic neuroendocrine tumor (see this term) that secretes vasoactive intestinal polypeptide (VIP) leading to the manifestations of watery diarrhea, hypokalemia and achlorhydia or hypochhlorhydia (known as WDHA syndrome). Epidemiology The incidence of VIPoma in the general population is of less than 1/10,000,000 individuals per year. ... Differential diagnosis Differential diagnoses include all other causes of chronic diarrhea such as malabsorption syndrome, Crohn disease, ulcerative colitis, microscopic colitis (see these terms), and gastrointestinal infections.
The American Optometric Association calls this computer vision syndrome. It's also called digital eyestrain. ... Computer use strains eyes more than reading print material because people tend to: Blink less while using computers, and blinking is key to moistening the eyes View digital screens at less than ideal distances or angles Use devices that have glare or reflection Use devices with poor contrast between the text and the background In some cases, an underlying eye problem, such as eye muscle imbalance or uncorrected vision, can cause or worsen computer vision syndrome. Some other factors that can make the condition worse include: Glare on the screen Poor posture Setup of a computer workstation Circulating air, such as from air conditioning or a nearby fan Complications Eyestrain doesn't have serious or long-term consequences, but it can be aggravating and unpleasant.
A number sign (#) is used with this entry because of evidence that a form of Klippel-Feil syndrome associated with nemaline myopathy and facial dysmorphism (KFS4) is caused by homozygous mutation in the MYO18B gene (607295) on chromosome 22q12. Description Klippel-Feil syndrome-4 with nemaline myopathy and facial dysmorphism is an autosomal recessive disorder characterized mainly by severe hypotonia apparent from infancy. ... For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (118100). Clinical Features Alazami et al. (2015) studied an unrelated Saudi boy and girl with Klippel-Feil syndrome who also exhibited myopathy, mild short stature, microcephaly, and distinctive facies. ... Malfatti et al. (2015) noted that Klippel-Feil syndrome was diagnosed during childhood in the patients reported by Alazami et al. (2015), whereas their Portuguese patient died at 4.5 months of age; radiographs were not performed on the patient reported by Malfatti et al. (2015). ... Molecular Genetics In a boy and a girl from unrelated consanguineous Saudi families with Klippel-Feil syndrome and myopathy, who were negative for mutation in Noonan syndrome (see 163950)-associated genes, Alazami et al. (2015) performed homozygosity mapping and found a single locus of identical haplotype spanning chr22:25641025-26665674 (GRCh37).
A rare genetic disease characterized by the association of Klippel-Feil anomaly (fusion of the cervical spine), myopathy, hypotonia, short stature, microcephaly, and facial dysmorphism (including low-set ears, bulbous nose, long philtrum, high-arched palate, and low posterior hairline, among others). Cardiac abnormalities and various skeletal anomalies (such as pectus excavatum or clinodactyly) have also been reported.
As a pioneer in the use of the light microscope in pathology, Virchow was the first to describe the abnormal excess of white blood cells in people with the clinical syndrome described by Velpeau and Bennett. ... "Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients" . ... PMID 9264391 . ^ Evans DI, Steward JK (December 1972). "Down's syndrome and leukaemia". Lancet . 2 (7790): 1322. doi : 10.1016/S0140-6736(72)92704-3 . ... CS1 maint: DOI inactive as of January 2021 ( link ) ^ Barzi A, Sekeres MA (January 2010). "Myelodysplastic syndromes: a practical approach to diagnosis and treatment". ... "Having a higher blast percentage in circulation than bone marrow: clinical implications in myelodysplastic syndrome and acute lymphoid and myeloid leukemias" .
A rare, acute myeloid leukemia characterized by evidence of granulocytic maturation and more than 20% of blast cells in the bone marrow and/or peripheral blood. The maturing non-blast granulocytic cells account for greater than or equal to 10% and monocytic cells less than or equal to 20% of the bone marrow cells. Various degrees of anemia, thrombocytopenia, or pancytopenia are present. Frequent clinical manifestations include fatigue, fever, bleeding disorders, and organomegaly, especially hepatosplenomegaly.