Arteriohepatic dysplasia (Alagille syndrome)

Alagille syndrome (AS) is the second most frequent cause of intrahepatic cholestasis in children under one year of age. The disease has an autosomal dominant mode of inheritance with reduced penetrance and variable expressivity. It has been stated that this form of biliary paucity has a good long-term prognosis, but recent studies have revealed that the syndrome may be accompanied by long-term manifestations extending beyond childhood. Based on a case story the syndrome is described, and the diagnostic criteria, treatment and prognosis of AS are discussed.     

Endocrinologic and metabolic complications of Alagille syndrome]

BACKGROUND: First language acquisition depends on intermodal perception, especially auditive, tactile-kinesthetic, and partly visual in addition to sensomotoric integration. The influence of the vestibular function for a physiological language development is still unknown. PATIENT: A case history of a child with bilateral aplasia of all semicircular canals, normacusis in the right ear, and severe sensorineural hearing loss in the left (hearing aid supplied), without mental deficiency, allows us to draw initial conclusions. RESULTS: Logopedic diagnostics revealed only a mild articulation disorder (interdental sigmatism, inconstant gammacism) as a possible consequence of recurrent middle ear effusions since early childhood. Language development diagnostics did not demonstrate any significant norm deviation. CONCLUSIONS: In contrast to the statomotoric disorder, no evidence for a specific language impairment was found. Our report elucidates the importance of a selected diagnostic imaging (spiral CT and MIP MRI) in the phoniatric-ped-audiological field.     

Linkage analysis and identification of deletion in Alagille syndrome gene

PURPOSE: There is concern that patients with presumed ulcerative colitis and significant perianal disease may in fact have Crohn's disease. Moreover, prior perianal disease may be an independent factor for poor outcome of the pelvic pouch. The aim of this study was to evaluate the effect of prior perianal disease on pelvic pouch outcome. METHODS: Between 1982 and 1994, 52 of 753 patients (6.9 percent) who had a pelvic pouch procedure were prospectively identified as having perianal disease. Outcome of the pelvic pouch of these 52 patients (Group I) were compared with the outcome of 701 pelvic pouch patients with no prior perianal disease (Group II). The perianal diseases identified in Group I were fissure-in-ano (17), perianal abscesses (13), fistula-in-ano (7), rectovaginal fistula (3), and significant hemorrhoids/skin tags (25). Eleven patients (21 percent) had more than one type of perianal disease. Twenty-seven patients (52 percent) required a total of 33 perianal operations for the different anal pathologies. RESULTS: Both groups were comparable for the following characteristics: age at time of pelvic pouch procedure, pathology (ulcerative colitis or indeterminate colitis), design of pouch, and type of ileoanal anastomosis (handsewn or stapled). An ileoanal anastomosis leak developed in 21 percent of patients (n = 11) in Group I vs. 11.4 percent (n = 80) in Group II (P < 0.05). Perianal postoperative complications occurred in 11.5 percent of patients (n = 6) in Group I vs. 1.7 percent (n = 12) in Group II (P < 0.05). Total pouch failure rate was not significantly different between the two groups (11.5 vs. 7.6 percent; P > 0.05). Crohn's disease was subsequently diagnosed in 1.9 vs. 2.7 percent (P > 0.05). Subgroup analysis of Group I patients showed no significant difference in outcome according to type of perianal lesion or a history of perianal surgery. CONCLUSION: Prior perianal disease significantly increases the risk of developing an ileoanal anastomotic leak and postoperative perianal complications. However, a pelvic pouch procedure may be an acceptable surgical alternative for selected ulcerative colitis patients with prior perianal disease because the overall pouch failure rate is not significantly increased.     

Mutational analysis of the Jagged 1 gene in Alagille syndrome families

Alagille syndrome (AGS) is an autosomal dominant disease characterized by five major abnormalities in the liver, heart, face, vertebrae and eye. The responsible gene has been recently identified as the human Jagged 1 (JAG1) gene, which encodes a ligand for the Notch receptor. We analyzed the JAG1 gene in eight AGS families, including affected and unaffected individuals, at the genomic DNA level, mainly by single-strand conformational polymorphism (SSCP) and DNA sequencing analysis. Four categories of mutations were identified: (i) four frameshift mutations in exons 9, 22, 24 and 26 were exhibited respectively in affected individuals of four AGS families, which resulted in moving the translational frame of JAG1; (ii) one nonsense mutation, a 1 bp substitution in exon 5 of the EGF-like repeat domain, was detected in two unrelated AGS families, which altered codon 235 from arginine to stop; (iii) one acceptor splice site mutation of exon 5 was revealed in a sporadic patient; and (iv) a 1.3 Mb deletion, which included the entire JAG1 gene, was found in another patient. Our results further demonstrate that AGS is a dominant disease and suggest that the JAG1 gene exerts a fundamental role in regulating genes involved in development.     

Training family psychologists: The family studies program at Georgia State University.

Describes the Family Studies Program, which has a 2-phased clinical practica format that combines theory and practice. The format is not fixed but will change as knowledge in the field increases. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

D-glyceric acidemia: biohcemical studies of a new syndrome

Studies of a mentally retarded boy, clinically suffering from nonketotic hyperglycinemia, are reported. Using combined gas chromatography-mass spectrometry, enzyme specificity studies, and spectropolariometry D-glyceric acid in extremely elevated concentrations was demonstrated in both serum and urine (serum: 1.0-1.3 mmol/liter, urine: 33-187 mmol/liter). Hydroxypyruvic acid was not detectable in urine from this boy using a gas chromatographic method with a limit of detection of 0.3 mmol/liter. Enzyme assays of D-glyceric dehydrogenase on blood leukocytes demonstrated significantly lower activity in the patient compared with five normal children.     

Laurence-Moon-Biedl syndrome (?) and Prader-Willi syndrome (?) in a single family

Mental retardation, hypogonadism, obesity, and abnormal blood sugar regulation were common findings in two siblings. In addition, the 17-year-old female patient showed short stature, muscular hypotonia in infancy, and small hands with tapering fingers suggesting Prader-Willi syndrome, and the 12-year-old male patient showed retinitis pigmentosa, normal height, and normal muscular tonicity suggesting Laurence-Moon-Biedl syndrome, though polydactyly was absent. Possible consideration was discussed.     

An Israeli family with six cisAB members: serologic and enzymatic studies

Multicentric melanomas in the same eye are rare, with few cases substantiated by histology and serial sectioning. We report a patient with two documented choroidal malignant melanomas in one eye. The initial tumor spontaneously decreased in size for over 2 years before a second tumor appeared in a noncontiguous location in the same eye. After enucleation, serial sections showed that the two lesions were independent choroidal melanomas. We review the literature regarding multiple, independent intraocular choroidal malignant melanomas.     

DNA testing for fragile X syndrome: implications for parents and family

The current discussion focuses on criticism as a positive force for improving epidemiologic practice through periodic reexamination of the basic approach to the discipline and the strategy for meeting the future educational needs of students and practicing epidemiologists. The types of epidemiologic research conducted and the settings within which the research will be conducted are also discussed. Epidemiology can be expected to play a major role in new areas of research that are created by changes in the medical care system and the development of large data systems associated with these approaches to health care delivery. This paper also discusses the growing threat to data access, the problems of communicating epidemiologic research findings to the public through the media, and the expanding interface between epidemiologic research and the legal system. The role of epidemiologic organizations in helping to shape the discipline's response to these issues and the opportunities these issues or problems present for improving epidemiologic research are also discussed.     

Nevoid basal-cell syndrome: literature review and case report in a family

The Nevoid Basal-Cell Carcinoma Syndrome (NBCC), or as it is also referred to, basal-cell nevus syndrome or Gorlin-Goltz syndrome, is characterized by multiple early-appearing basal cell carcinomas, keratocytosis of the mandible, and anomalies of the ocular, skeletal reproductive system. We describe four patients in the same family, all of them possessing a large number of skin tumors associated with other typical clinical and X-Ray anomalies of NBCC. The definitive treatment of NBCC has yet to be established, however, early diagnosis is very important as well as the periodical follow-up examination of ten patients, mainly due to the transformations in the skin lesions that may occur.     

Pfeiffer syndrome: report of a family and review of the literature

A 5-year-old boy and his father with Pfeiffer syndrome are described. They had acrocephaly, hypertelorism, antimongoloid slant of the palpebral fissures, protrusion of the eyes, large and broad nose, small mandible, irregularly placed teeth, additional upper canine, high-arched palate, partial syndactyly of fingers and toes, brachydactyly of toes, valgus deformity of hypertrophied triangular great toes, broad phalanges of the great toes and broad first metatarsals, accessory epiphyses lateral to the interphalangeal joint of the great toes, and normal intelligence. To our knowledge, this is the first family in which the syndrome is almost totally confined to the head and feet--it spares the upper limbs except for partial skin syndactyly between the fingers--and the third family showing inheritance through three successive generations suggesting an autosomal dominant mode of inheritance. The published papers are reviewed and the clinical and x-ray signs are tabulated.     

Marinesco-Sj?gren syndrome in a Bedouin family

Marinesco-Sj?gren syndrome is rarely reported in the Middle East. This is the 2nd report of Marinesco-Sj?gren syndrome in an Arab family. The clinical features of 2 affected brothers are described. Electrophysiological studies of the 2 patients showed primarily myopathic changes, whereas sural nerve biopsy revealed segmental demyelination and axonal degeneration. The role of tissue biopsy and the relationship to different electrophysiological studies are discussed. Both patients were noticed to have abnormally short lateral 3 metatarsals, a feature not present in other healthy members of the family. We suggest that this feature should be considered part of the syndrome profile.     

Aarskog syndrome: report of a family with review and discussion of nosology

Five individuals in one family, including dizygotic male twins, a half brother and their mother, had Aarskog syndrome (AS). Phenotypic variability is wide not only between mother and sons but also between sibs. Collectively, the affected relatives have the full spectrum of findings seen in AS. Based on analysis of this family and others from the literature, we derive primary and secondary diagnostic criteria for AS. Primary criteria include: short stature, hypertelorism, short nose with anteverted nares, maxillary hypoplasia, a crease below the lower lip, mild interdigital webbing with short and broad hands, short fifth finger with clinodactyly, and shawl scrotum. Secondary criteria include: abnormal auricles with fleshy lobules, posteriorly angulated ears, widow's peak, ptosis, downward slant of palpebral fissures, joint hyperextensibility, broad feet with bulbous toes, cryptorchidism, inguinal hernia, and prominent umbilicus. Literature pertaining to the clinical manifestations and genetics of AS is reviewed and nosology of similar syndromes is discussed.