For a general phenotypic description and a discussion of genetic heterogeneity of eosinophilic esophagitis, see EOE1 (610247). Mapping Rothenberg et al. (2010) genotyped approximately 550,000 genomewide SNPs in a discovery cohort of 181 eosinophilic esophagitis (EOE) cases and 1,974 controls and a replication cohort of 170 EOE cases and 1,130 controls. Significant association was found with variants at a region on chromosome 5q22 encompassing the TSLP (607003) and WDR36 (609669) genes (combined p = 3.19 x 10(-9) for rs3806932). Analysis of esophageal biopsies revealed that TSLP was significantly overexpressed in EOE cases compared to controls (p less than 0.0001 for TSLP isoform 2), whereas WDR36 was unchanged. TSLP expression levels were also significantly correlated with the rs3806932 genotype in EOE cases, with homozygote carriers of the protective minor G allele showing less TSLP expression than heterozygotes or homozygotes for the ancestral allele.
Overview Eosinophilic esophagitis (e-o-sin-o-FILL-ik uh-sof-uh-JIE-tis) is a chronic immune system disease. With this disease, a type of white blood cell, called an eosinophil, builds up in the lining of the tube that connects your mouth to your stomach. This tube is also called the esophagus. This buildup, which is a reaction to foods, allergens or acid reflux, can inflame or injure the esophageal tissue. Damaged esophageal tissue can lead to difficulty swallowing or cause food to get stuck when you swallow. Eosinophilic esophagitis has been identified only since the early '90s, but is now considered a major cause of digestive system illness.
Differential diagnosis Differential diagnoses include gastroesophageal reflux disease, esophageal candidiasis and other local and systemic causes of esophageal eosinophilia (including eosinophilic gastroenteritis and hypereosinophilic syndrome, Crohn's disease involving the esophagus, parasite infectations, drug hypersensitivity, achalasia, vasculitis, phenphigoid, connective tissue disorders and graft-versus-host disease).
Description Eosinophilic esophagitis (EOE) has an incidence of approximately 1 per 10,000 people. Symptoms include difficulty feeding, failure to thrive, vomiting, epigastric or chest pain, dysphagia, and food impaction. Individuals with EOE are predominantly young males with a high rate of atopic disease, and the diagnosis is made by endoscopy and biopsy findings of isolated eosinophils in the esophagus (summary by Rothenberg et al., 2010). Genetic Heterogeneity of Eosinophilic Esophagitis Eosinophilic esophagitis-1 (EOE1) is associated with variation at chromosome 7q11.2. Another locus (EOE2; 613412) has been been associated with variation in the TSLP gene (607003) on chromosome 5q22.
The chin showed a grooving like that seen in the Freeman-Sheldon syndrome (193700) but the patients did not have other features of that syndrome. ... Molecular genetic analysis ruled out a clinically similar disorder caused by reciprocal 6q/9p translocation, Haspeslagh syndrome (177980). Wortmann et al. (2007) stated that this patient was most similar to the patient described by Chitayat et al. (1991), although he had some features in common with the patient reported by Chitayat et al. (1990).
Clinical Features This trait is likely to have many causes. It is a feature of Book syndrome (112300), Waardenburg syndrome (193500), Lison syndrome (270750), and pernicious anemia.
As hair pigmentation is a result of complex interaction between various genetic factors, it is thought that premature greying could be due to exhaustion of melanocyte 's capability to produce hair pigmentation. [1] Premature canities may occur alone as an autosomal dominant condition or in association with various autoimmune or premature aging syndromes . Down syndrome ( trisomy 21) is characterized by features of accelerated aging including premature greying of hair and deficient DNA repair . [5] Premature greying needs to be differentiated from various genetic hypomelanotic hair disorders. ... "Trisomy 21 and accelerated aging: DNA-repair parameters in peripheral lymphocytes of Down's syndrome patients". Mechanisms of Ageing and Development . 100 (1): 85–101. doi : 10.1016/s0047-6374(97)00121-8 .
A number sign (#) is used with this entry because ichthyosis bullosa of Siemens (IBS) is caused by heterozygous mutation in the KRT2 gene (600194) on chromosome 12q13. Clinical Features Schnyder (1970) concluded that the bullous type of ichthyosis, called ichthyosis bullosa of Siemens (Siemens, 1937), represents a distinct entity. IBS is a rare autosomal dominant disorder that is highly penetrant and clinically evident from birth. In affected individuals, the clinical findings are similar to those of epidermolytic hyperkeratosis (EHK; 113800). IBS patients are born with a generalized reddening of the skin (erythema) and widespread blistering.
Urachal sinus is a type of congenital urachal anomaly (see this term) resulting from the failure of the umbilical end of the urachus to close, without continuity to the bladder, and that is usually asymptomatic but can present with continuous cloudy umbilical discharge, tender midline infraumbilical mass and fever when infected.
Congenital [ edit ] Congenital causes include: Klippel Trenaunay Weber syndrome Maffucci syndrome macrodystrophia lipomatosa [1] neurofibromatosis , [2] [3] lipoatrophic diabetes . [4] Proteus syndrome , which by one theory accounts for the deformities of the Elephant Man Acquired [ edit ] There are a number of acquired causes of local gigantism.
A rare disorder characterized by a group of symptoms that may be observed in a foetus or newborn when the mother was exposed during pregnancy to excessive amounts of methylmercury. Epidemiology Accidents have led to the birth of about 800 affected children worldwide over the last 50 years. Clinical description In the late-1950s, methylmercury toxicity became highly publicised after an outbreak of cerebral palsy and microcephaly in newborns from the fishing village of Minimata Bay, Japan. These abnormalities were caused by methylmercury contamination of fish in the bay, and were termed Minimata Disease. Similar intoxications also occurred in Iraq after seeds contaminated with methylmercury were mistakenly used to make bread.
They required that patients must exhibit all symptoms of Hunter-Russell syndrome – the standard diagnosis of organic mercury poisoning at the time, which originated from an industrial accident in the United Kingdom in 1940. The committee certified only patients exhibiting explicit symptoms of the British syndrome, rather than basing their diagnosis on the disease in Japan.
Junctional epidermolysis bullosa with pyloric atresia is a severe subtype of junctional epidermolysis bullosa (JEB, see this term) characterized by generalized blistering at birth and congenital atresia of the pylorus and rarely of other portions of the gastrointestinal tract. Epidemiology Prevalence is unknown. More than 100 cases have been reported worldwide. Clinical description Skin manifestations include severe blistering, atrophic scarring, and nail dystrophy. Congenital absence of skin (aplasia cutis congenita) is present in approximately 20% of cases, and ear anomalies are also relatively common. The manifestations of pyloric atresia include vomiting, abdomen distension, and an absence of stools.
According to the 2014 classification system, the four major types of EB, caused by pathogenic variants in 18 different genes, are EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), and Kindler syndrome (KS) [Fine et al 2014]. Classification into major type is based on the location of blistering in relation to the dermal-epidermal junction of skin.
Epidermolysis bullosa with pyloric atresia (EB-PA) is a condition that affects the skin and digestive tract. This condition is one of several forms of epidermolysis bullosa, a group of genetic conditions that cause the skin to be fragile and to blister easily. Affected infants are often born with widespread blistering and areas of missing skin. Blisters continue to appear in response to minor injury or friction, such as rubbing or scratching. Most often, blisters occur over the whole body and affect mucous membranes such as the moist lining of the mouth and digestive tract.
Carey et al. (1983) suggested that the designation 'aplasia cutis congenita' was inappropriate because it usually entails involvement of the scalp predominantly or exclusively; they suggested the eponymic designation Carmi syndrome. One of the twins had axillary pterygia and bilateral lower lid ectropion, whereas the other showed esophageal atresia. ... Maman et al. (1998) provided detailed clinical and histopathologic information on 8 cases of the triple syndrome epidermolysis bullosa/pyloric atresia/aplasia cutis congenita (EB-PA-ACC).
The clinical symptoms may be mistaken for hypocalcified amelogenesis imperfecta, congenital erythropoietic porphyria, conditions leading to early tooth loss (Kostmann syndrome, cyclic neutropenia, Chediak-Hegashi syndrome, Langerhans cell histiocytosis, Papillon-Lefèvre syndrome), vitamin D-resistant rickets (see these terms), as well as permanent teeth discoloration due to tetracyclines, and vitamin D-dependent rickets.
Dentinogenesis imperfecta type 2 is a rare and severe form of dentinogenesis imperfecta , a condition that affects tooth development. People affected by the condition may have weak and discolored teeth. These problems can affect both primary (baby) teeth and permanent teeth. People with this form of dentinogenesis imperfecta have no normal teeth. Sensorineural hearing loss has also been found in some affected people. Dentinogenesis imperfecta type 2 is caused by changes (mutations) in the DSPP gene and is inherited in an autosomal dominant manner.
A number sign (#) is used with this entry because this syndrome of dentinogenesis imperfecta and deafness is caused by mutations in the DSPP gene (125485) on chromosome 4q21. ... The deafness in the DGI1/DFNA39 syndrome described by Xiao et al. (2001) had its start in the high frequency range at an age of 20 to 30 years.
A number sign (#) is used with this entry because dentinogenesis imperfecta-1 is caused by mutation in the DSPP gene (125485), encoding dentin phosphoprotein and dentin sialoprotein. Dentinogenesis imperfecta is an entity clearly distinct from osteogenesis imperfecta with opalescent teeth, and affects only the teeth. There is no increased frequency of bone fractures in this disorder. The frequency may be 1 in 6000 to 8000 children (Witkop, 1957). Witkop and Rao (1971) preferred the term opalescent dentin for this condition as an isolated trait, reserving dentinogenesis imperfecta for the trait when it is combined with osteogenesis imperfecta. Large kindreds have been reported (Roberts and Schour, 1939; Johnson et al., 1959; Bixler et al., 1969; Giansanti and Budnick, 1975; Mars et al., 1976).
The pain associated to these lesions is often disproportionate to their size. [6] The syndrome occurs predominantly in middle-aged women with poorly controlled hypertension in the form of skin ulcers on the anterolateral aspect of the lower legs. ... "Lumbar Sympathectomy in the Treatment of Hypertensive Isehemic Ulcers of the Leg (Martorell's Syndrome)" . Circulation . 12 (2): 239–241. doi : 10.1161/01.cir.12.2.239 . ... "Diastolic arterial hypertension and ulcer of the leg: Martorell's syndrome". Lancet . 266 (6821): 1059. doi : 10.1016/S0140-6736(54)91622-0 .
A urachal cyst is a sac-like pocket of tissue that develops in the urachus , a primitive structure that connects the umbilical cord to the bladder in the developing baby. Although it normally disappears prior to birth, part of the urachus may remain in some people. Urachal cysts can develop at any age, but typically affect older children and adults. Urachal cysts are often not associated with any signs or symptoms unless there are complications such as infection. In these cases, symptoms may include abdominal pain, fever, pain with urination and/or hematuria .
Urachal cyst is a congenital urachal anomaly (see this term) characterized by a failure of complete closure of the urachus, in which both ends are closed but the central lumen remains patent. It is typically asymptomatic but may become clinically significant when infected, presenting as a mass in the umbilical region accompanied by abdominal pain and fever.
The third sib had no ptosis but presented with bilateral Duane retraction syndrome, exotropic in the right eye and esotropic in the left. ... An unrelated patient with the disorder presented with exotropic Duane retraction syndrome. Inheritance The transmission pattern of CFEOM5 in the family reported by Shinwari et al. (2015) was consistent with autosomal recessive inheritance. ... INHERITANCE - Autosomal recessive HEAD & NECK Eyes - Abnormal ocular motility - Duane retraction syndrome - Ptosis - Dysinnervation of various cranial nerves to ocular muscles MISCELLANEOUS - Congenital onset - Two unrelated families have been reported (last curated February 2015) MOLECULAR BASIS - Caused by mutation in the collagen, type XXV, alpha-1 gene (COL25A1, 610004.0001 ) ▲ Close
Congenital ptosis is characterized by superior eyelid drop present at birth. Epidemiology Prevalence is unknown. Etiology Isolated congenital ptosis is unilateral in 75% of the cases. Genetic counseling Two patterns of inheritance have been described in familial cases: autosomal dominant and X-linked. Management and treatment A medical or surgical treatment can potentially be proposed, depending on the severity of ptosis.
Thus this disorder is distinct from the blepharophimosis syndrome (110100), which maps to 3q, and from congenital fibrosis of the extraocular muscles (135700), which maps to chromosome 12. ... The rectus superior muscle may also be involved; (2) ptosis with blepharophimosis, also due to faulty peripheral differentiation and transmitted as a dominant; (3) ptosis due to ophthalmoplegia (e.g., 165000) usually of central origin; (4) ptosis associated with myasthenia gravis and myotonia, both rare as congenital disorders; (5) ptosis due to congenital sympathetic palsy; (6) synkinetic ptosis (see Marcus Gunn phenomenon, 154600); and (7) intermittent pseudo-ptosis associated with the retraction syndrome. The extensive Metcalf kindred in Lafayette, Tennessee, has hereditary congenital ptosis (Briggs, 1919).
See PTOS1 (178300) for a form of ptosis that has been linked to chromosome 1p. Clinical Features McMullan et al. (2000) analyzed a large Caucasian pedigree from the southwest of England with dominant congenital isolated ptosis and found linkage to the X chromosome. There was no evidence of blepharophimosis, epicanthus inversus, or prevailing ocular motility disorder. The ptosis was strikingly symmetric and equal in both male and female family members. Affected family members were born with bilateral ptosis which resulted in an abnormally low lid position that almost impinged on the visual axis in the primary position of gaze.
Clinical description Four types of brachyolmia have been described: autosomal recessive brachyolmia, Hobaek/Toledo type, autosomal recessive brachyolmia-amelogenesis imperfecta syndrome, autosomal dominant brachyolmia, and autosomal recessive brachyolmia, Maroteaux type (see these terms). ... In AR brachyolmia-amelogenesis imperfecta syndrome, short-trunked short stature is associated with platyspondyly and enamel abnormalities. ... Differential diagnosis The differential diagnosis includes other genetic skeletal dysplasia syndromes, particularly mild spondyloepiphyseal dysplasia, including mild type 2 collagenopathy and mild Morquio disease (see this term).
Hypotrichosis with juvenile macular degeneration (HJMD) is a very rare syndrome characterized by sparse and short hair from birth followed by progressive macular degeneration leading to blindness. Epidemiology Prevalence is unknown but approximately 50 patients have been described since the first characterization of the syndrome in 1935. Clinical description HJMD patients present with short and sparse scalp hair since birth or first months of life, with no subsequent growth during life. ... Differential diagnosis Differential diagnosis includes EEM syndrome, also caused by CDH3 mutations.
Mutations in the CDH3 gene can also appear in EEM syndrome . Treatment [ edit ] There is no treatment for the disorder. ... S2CID 21073109 . Sources [ edit ] "A Rare Syndrome: Hypotrichosis with Juvenile Macular Dystrophy (HJMD)" .
The parents of these patients were born in the same Portuguese village, suggesting autosomal recessive inheritance of the syndrome. Absence of digital abnormalities and normal eyelashes and eyebrows distinguish this syndrome from the EEM syndrome (225280).
The cause is unknown, but pathology reveals inadequate blood flow resulting in ischemia and fibrosis . [ citation needed ] Lattice degeneration occurs in approximately 6–8% of the general population and in approximately 30% of phakic retinal detachments. [1] Similar lesions are seen in patients with Ehlers-Danlos syndrome , Marfan syndrome , and Stickler syndrome , all of which are associated with an increased risk of retinal detachment .