Evaluation of 100 Esophageal Motility Studies at a University Medical Center

100 esophageal motility studies on 88 consecutive patients referred to the University of California Medical Center were analyzed. Diagnoses of achalasia, diffuse spasm of the esophagus, scleroderma, hiatal hernia and other conditions were made from the motility tracings. The motility tests have been found to be most helpful in differentiating various disorders of swallowing and thoracic pain of unknown cause.     

The contribution of CLIP2 haploinsufficiency to the clinical manifestations of the Williams-Beuren syndrome

Williams-Beuren syndrome is a rare contiguous gene syndrome, characterized by intellectual disability, facial dysmorphisms, connective-tissue abnormalities, cardiac defects, structural brain abnormalities, and transient infantile hypercalcemia. Genes lying telomeric to RFC2, including CLIP2, GTF2I and GTF2IRD1, are currently thought to be the most likely major contributors to the typical Williams syndrome cognitive profile, characterized by a better-than-expected auditory rote-memory ability, a relative sparing of language capabilities, and a severe visual-spatial constructive impairment. Atypical deletions in the region have helped to establish genotype-phenotype correlations. So far, however, hardly any deletions affecting only a single gene in the disease region have been described. We present here two healthy siblings with a pure, hemizygous deletion of CLIP2. A putative role in the cognitive and behavioral abnormalities seen in Williams-Beuren patients has been suggested for this gene on the basis of observations in a knock-out mouse model. The presented siblings did not show any of the clinical features associated with the syndrome. Cognitive testing showed an average IQ for both and no indication of the Williams syndrome cognitive profile. This shows that CLIP2 haploinsufficiency by itself does not lead to the physical or cognitive characteristics of the Williams-Beuren syndrome, nor does it lead to the Williams syndrome cognitive profile. Although contribution of CLIP2 to the phenotype cannot be excluded when it is deleted in combination with other genes, our results support the hypothesis that GTF2IRD1 and GTF2I are the main genes causing the cognitive defects associated with Williams-Beuren syndrome.     

The problem of the acquired short esophagus; report of 18 patients

A shortened esophagus is probably acquired, rather than congenital, in the great majority of cases. The process by which the shortening develops, as described by Allison and his coworkers, begins with esophageal hiatal hernia, followed by esophagitis caused by the irritation of acids from the stomach, then recurrent ulceration and healing which forms scar tissue which little by little shortens the esophagus. Obesity and relaxation of the supporting musculotendinous structures which accompany advancing years probably are contributory factors in production of esophageal hiatal hernia. Fifteen of a series of 18 patients noted the onset of symptoms on or after the age of 45. Roentgen examination of the esophagus and stomach is indispensable in establishing a diagnosis of acquired short esophagus. Esophagoscopic examination is even more important. In some cases endoscopic differentiation between acute inflammation and carcinoma is difficult. In such circumstances examination of a biopsy specimen taken from the gastric mucosa immediately distal to the area of inflammation or stricture may be helpful. Results in eight patients with advanced esophageal shortening and stricture who were treated conservatively indicate that this should be tried before surgical treatment is considered. For patients with esophageal hiatal hernia accompanied by shortening of the esophagus that is just beginning to produce symptoms, early repair is indicated, since the condition is progressive and the surgical problem is much simpler in the early stages.     

A new case of DOOR syndrome

We present the case of a 9-year-old boy with DOOR syndrome recognized in the first year of his life because of a delayed development of speech. The diagnosis was based on characteristic abnormalities, including congenital deafness, nail and bone abnormalities, and mild mental retardation.     

ESOPHAGEAL HIATAL HERNIA—Some Aspects of Surgical Treatment

Patients with esophageal hiatal hernia often have an array of distressing complaints and physical signs that are difficult to interpret. Physiologic and anatomic studies of the gastroesophageal area in the region of the esophageal hiatus of the diaphragm indicate the existence of a three-in-line sphincter group, consisting of the inferior esophageal constrictor, diaphragmatic pinchcock and cardioesophageal junction. These mechanisms, acting in unison, prevent regurgitation in normal persons.It also can be deduced from clinical, radiologic and experimental data that anatomic disturbances at the esophageal hiatus account for physiologic alterations. A reasonable explanation for the symptoms and signs of esophageal hiatal hernia can be made on the basis of the functional competence of the three-in-line sphincter mechanisms.     

A Win at Short Odds

Patients with esophageal hiatal hernia often have an array of distressing complaints and physical signs that are difficult to interpret. Physiologic and anatomic studies of the gastroesophageal area in the region of the esophageal hiatus of the diaphragm indicate the existence of a three-in-line sphincter group, consisting of the inferior esophageal constrictor, diaphragmatic pinchcock and cardioesophageal junction. These mechanisms, acting in unison, prevent regurgitation in normal persons.It also can be deduced from clinical, radiologic and experimental data that anatomic disturbances at the esophageal hiatus account for physiologic alterations. A reasonable explanation for the symptoms and signs of esophageal hiatal hernia can be made on the basis of the functional competence of the three-in-line sphincter mechanisms.     

The role of hiatus hernia in GERD

Increased esophageal acid exposure in gastroesophageal reflux disease has several potential causes, some related primarily to physiological dysfunction of the LES and others related to anatomic distortion of the gastroesophageal junction as occurs with hiatus hernia. One attractive feature of implicating hiatal hernias in the pathogenesis of reflux disease is that, like reflux disease, axial hernias become more common with age and obesity. However, the importance of hiatus hernia is obscured by imprecise definition and an all-or-none conceptualization that has led to wide variation in estimates of prevalence among normal or diseased populations. There are at least three potentially significant radiographic features of a hiatus hernia: axial length during distention, axial length at rest, and competence of the diaphragmatic hiatus. Although any or all of these features may be abnormal in a particular instance of hiatus hernia, each is of different functional significance. Grouping all abnormalities of the gastroesophageal junction as "hiatus hernia" without detailing the specifics of each case defies logic. Mechanistically, the gastroesophageal junction must protect against reflux both in static and dynamic conditions. During abrupt increases in intra-abdominal pressure, the crural diaphragm normally serves as a "second sphincter," and this mechanism is substantially impaired in individuals with a gaping hiatus. Large, non-reducing hernias also impair the process of esophageal emptying, thereby prolonging acid clearance time following a reflux event (especially while in the supine posture). These anatomically-determined functional impairments of the gastroesophageal junction lead to increased esophageal acid exposure. Thus, although hiatus hernia may or may not be an initiating factor at the inception of reflux disease, it clearly can act as a sustaining factor accounting for the frequently observed chronicity of the disease.     

An additional manifestation in acrocallosal syndrome: temporal lobe hypoplasia

Acrocallosal Syndrome is a rare genetic disorder which is characterized by moderate to severe mental retardation, agenesis or hypoplasia of the corpus callosum and polydactyly of fingers and toes. The spectrum of this syndrome is very variable. Prominent forehead, broad nasal bridge, short nose and mandible, hypertelorism, epicanthic folds, large anterior fontanelle and tapered fingers, omphalocele and inguinal hernia are some other common findings in this syndrome. Twenty percent of the patients have associated brain abnormalities such as cerebral atrophy, hypothalamic dysfunction, small cerebrum, micropolygyria, hypoplasia of pons, hypoplasia of cerebellar hemispheres, hypoplasia of medulla oblongata, agenesis or hypoplasia of cerebellar vermis and corpus callosum abnormalities. Here we present a 10-month-old female infant with clinical and radiological findings indicative of acrocallosal syndrome. She was noted to have craniofacial abnormalities suggestive of acrocallosal syndrome, optic atrophy and polydactyly. MRI revealed cerebral atrophy, corpus callosum agenesis, dilated lateral ventricules and unilateral right temporal lobe hypoplasia, the latter not previously reported in the spectrum of this syndrome. Based on this observation we conclude the importance of screening brain abnormalities and present temporal lobe hypoplasia as a new additional anomaly in this syndrome.     

THE PROBLEM OF THE ACQUIRED SHORT ESOPHAGUS—Report of 18 Patients

A shortened esophagus is probably acquired, rather than congenital, in the great majority of cases. The process by which the shortening develops, as described by Allison and his coworkers, begins with esophageal hiatal hernia, followed by esophagitis caused by the irritation of acids from the stomach, then recurrent ulceration and healing which forms scar tissue which little by little shortens the esophagus.Obesity and relaxation of the supporting musculotendinous structures which accompany advancing years probably are contributory factors in production of esophageal hiatal hernia. Fifteen of a series of 18 patients noted the onset of symptoms on or after the age of 45.Roentgen examination of the esophagus and stomach is indispensable in establishing a diagnosis of acquired short esophagus. Esophagoscopic examination is even more important. In some cases endoscopic differentiation between acute inflammation and carcinoma is difficult. In such circumstances examination of a biopsy specimen taken from the gastric mucosa immediately distal to the area of inflammation or stricture may be helpful.Results in eight patients with advanced esophageal shortening and stricture who were treated conservatively indicate that this should be tried before surgical treatment is considered. For patients with esophageal hiatal hernia accompanied by shortening of the esophagus that is just beginning to produce symptoms, early repair is indicated, since the condition is progressive and the surgical problem is much simpler in the early stages.     

Potentialities of computed tomography in the diagnosis of hiatal hernia

An analysis of the results of 98 studies has demonstrated the potentialities of X-ray computed tomography in the diagnosis of hiatal hernia (HH), provided the X-ray computed tomography (XCT) semiotics of HH. It has found that XCT may directly visualize and objectively evaluate anatomic structures, such as diagraphmatic crus and esophageal foremen. It has emphasized that when XCT of abdominal and thoracic organs is performed, it is necessary to include the areas of diagragmatic curs and esophageal foramen into the list of anatomic structures binding for visual assessment and characterization, which in combination with other studies will assist in the early diagnosis of hiatal hernia and eventually expand the potentialities of XCT to a greater extent.     

Full incorporation of Strattice(TM) Reconstructive Tissue Matrix in a reinforced hiatal hernia repair: a case report

ABSTRACT: INTRODUCTION: A non-cross-linked porcine acellular dermal matrix was used to reinforce an esophageal hiatal hernia repair. A second surgery was required 11 months later to repair a slipped Nissen; this allowed for examination of the hiatal hernia repair and showed the graft to be well vascularized and fully incorporated. CASE PRESENTATION: A 71-year-old Caucasian woman presented with substernal burning and significant dysphagia. An upper GI series revealed a type III complex paraesophageal hiatal hernia. She underwent laparoscopic surgery to repair a hiatal hernia that was reinforced with a xenograft (StratticeTM Reconstructive Tissue Matrix, LifeCell, Branchburg, NJ, USA) along with a Nissen fundoplication. A second surgery was required to repair a slipped Nissen; this allowed for examination of the hiatal repair and graft incorporation 11 months after the initial surgery. CONCLUSION: In this case, a porcine acellular dermal matrix was an effective tool to reinforce the crural hiatal hernia repair. The placement of the mesh and method of fixation are believed to be crucial to the success of the graft. It was found to be well vascularized 11 months after the original placement with no signs of erosion, stricture, or infection. Further studies and longterm follow-up are required to support the findings of this case report.     

ENDOSCOPY IN HERNIA AT THE ESOPHAGEAL HIATUS

Endoscopy is useful for confirming diagnosis of hiatal hernia as made by x-ray examination, for establishing the diagnosis when x-ray examinations do not disclose the herniation, and for observation of resultant abnormalities in the affected area. The authors'' experience with gastroscopy and esophagoscopy in hiatal hernia is reported and the techniques and usual findings in these procedures are summarized.     

Chronic cough and gastroesophageal reflux.

We reviewed the charts of 20 patients with chronic cough of unknown cause who had been referred to a tertiary care respiratory centre from 1980 to 1984 to determine whether gastroesophageal reflux (GER) was a contributing factor. Fifteen of the patients complained of symptoms suggestive of GER: radiologic investigation of the upper gastrointestinal tract revealed hiatus hernia and GER in four, hiatus hernia alone in three, GER alone in two, decreased esophageal peristalsis in one and normal findings in four. Fibreoptic bronchoscopy in the four former smokers and one nonsmoker showed diffuse mucosal erythema. A chest x-ray film in one patient showed an infiltrate at the base of the right lung; transbronchial biopsy revealed vegetable material, which confirmed pulmonary aspiration. A 3-month course of medical antireflux treatment (dietary and lifestyle changes, elevation of the head of the bed and administration of cimetidine, antacid and metoclopramide) relieved the chronic cough in 14 of the 20 patients. Of the remaining patients one was lost to follow-up and five had GER confirmed by means of esophagoscopy, esophageal motility testing and long-term intraesophageal pH monitoring; four of the five patients underwent fundoplication and were asymptomatic 3 months after surgery. Antireflux therapy should be considered in patients with chronic cough when other causes have been ruled out, even if there are no GER symptoms. If the treatment fails, full investigation for GER is recommended; if GER is confirmed, surgery should be considered.     

A novel mutation in the RPS6KA3 gene in a patient with Coffin-Lowry syndrome

Coffin-Lowry syndrome is an X-linked disorder characterized by mental retardation, characteristic facial features, skeletal abnormalities, and tapering fingers. Herein we report a novel missense mutation in exon 7 at codon 180 in the RPS6KA3 gene in a boy with Coffin-Lowry syndrome.     

Williams-Beuren syndrome: a model of recurrent genomic mutation

Williams-Beuren syndrome is a segmental aneusomy syndrome with manifestations affecting the vascular, connective tissue, endocrine and central nervous systems. Most patients show a similar heterozygous approximately 1.5 Mb deletion at 7q11.23 that contains a number of reported genes. Deletion mapping in the few atypical patients with smaller deletions suggested that additive effects of haploinsufficiency for two or more genes might be necessary for the phenotype. Vascular stenoses are caused by haploinsufficiency at the elastin gene, while the genes responsible for the cognitive deficits are likely located at the telomeric edge of the deletion, including CYLN2 and GTF2I. Large region-specific segmental duplications predispose to misalignment and inter- or intrachromosomal unequal crossing-over causing the deletions. Atypical alleles at 7q11.23 such as inversions and deletions/insertions of large repeats, also generated through aberrant recombination between the local segmental duplications, are found in approximately 35% of transmitting parents. Genomic instability at 7q11.23 is directly related to the genomic structure of the region.     

Connection between elastin haploinsufficiency and increased cell proliferation in patients with supravalvular aortic stenosis and Williams-Beuren syndrome

To elucidate the pathomechanism leading to obstructive vascular disease in patients with elastin deficiency, we compared both elastogenesis and proliferation rate of cultured aortic smooth-muscle cells (SMCs) and skin fibroblasts from five healthy control subjects, four patients with isolated supravalvular aortic stenosis (SVAS), and five patients with Williams-Beuren syndrome (WBS). Mutations were determined in each patient with SVAS and in each patient with WBS. Three mutations found in patients with SVAS were shown to result in null alleles. RNA blot hybridization, immunostaining, and metabolic labeling experiments demonstrated that SVAS cells and WBS cells have reduced elastin mRNA levels and that they consequently deposit low amounts of insoluble elastin. Although SVAS cells laid down approximately 50% of the elastin made by normal cells, WBS cells deposited only 15% of the elastin made by normal cells. The observed difference in elastin-gene expression was not caused by a difference in the stability of elastin mRNA in SVAS cells compared with WBS cells, but it did indicate that gene-interaction effects may contribute to the complex phenotype observed in patients with WBS. Abnormally low levels of elastin deposition in SVAS cells and in WBS cells were found to coincide with an increase in proliferation rate, which could be reversed by addition of exogenous insoluble elastin. We conclude that insoluble elastin is an important regulator of cellular proliferation. Thus, the reduced net deposition of insoluble elastin in arterial walls of patients with either SVAS or WBS leads to the increased proliferation of arterial SMCs. This results in the formation of multilayer thickening of the tunica media of large arteries and, consequently, in the development of hyperplastic intimal lesions leading to segmental arterial occlusion.     

Atypical Deletion in Williams-Beuren Syndrome Critical Region Detected by MLPA in a Patient with Supravalvular Aortic Stenosis and Learning Difficulty

Williams-Beuren syndrome (WBS) is a genetic disease characterized by distinct facial features,short stature,hypotonia,mental retardation,overfriendly and hyper-social behavior,congenital heart disease,infantile hypercalcemia,arterial hypertension and other variable clinical manifestations in organs and systems such as the kidneys,eyes,gastrointestinal and osteoarticular systems (Morris and Mervis,2000).This mental retardation syndrome occurs in 1/20,000 live births (Meyer-Lindenberg et al.,2006).It is caused by a 1.55-1.84 Mb microdeletion in 7q 11.23,a region containing approximately 28genes.Depending on the genes deleted,the phenotypes of WBS patients range from isolated supravalvular aortic stenosis (SVAS) to full expression of the WBS characteristics.Most cases are sporadic (Ewart et al.,1993;Perez Jurado et al.,1996).     

Marden-Walker syndrome: case report, nosologic discussion and aspects of counseling

The Marden-Walker syndrome is characterized by a mask-like face with blepharophimosis, micrognathia, cleft or high-arched palate, low-set ears, congenital joint contractures, decreased muscular mass, failure to thrive and psychomotor retardation. We report a boy with a phenotype mostly resembling the condition named Marden-Walker syndrome, with many of the criteria proposed for diagnosing this particular phenotype. In addition he had hypoplastic corpus callosum, cerebellar vermis hypoplasia, enlarged cisterna magna and vertebral abnormalities. During pregnancy there were reduced fetal movements. In the present patient the fetal hypokinesia sequence, due to central nervous system malformation, is most compatible with the diagnosis of Marden-Walker syndrome. The etiology is probably heterogeneous, but the possibility of autosomal recessive inheritance should be considered in genetic counseling.     

Communicative competence and behavioural phenotype in children with Smith-Magenis syndrome

Smith-Magenis syndrome is characterized by a range of minor physical and facial abnormalities and is caused by a de novo deletion on chromosome 17. Most children function in the moderate to severe ranges of mental retardation. Results of a survey on adaptive skills, communicative competence and behavioural abnormalities in 20 children are reported. The findings suggest a strong desire to get in social contact and maintain conversations in spite of their limited cognitive processing. As a group, children with SMS are presenting with severe behavioural abnormalities, e.g. self-injury, extreme irritability, ritualistic behaviour. Behaviour problems are more severe than in other genetic syndrome groups as a comparison with Prader-Willi- and Fragile-X-syndrome children reveals. However, functional analysis suggests that it is not independent from situational variables. There is a strong need for behavioural intervention planning as part of family services.