Schinzel acrocallosal syndrome: a variant example of the Greig syndrome?

A 5-month-old male is reported with clinical and radiological findings identical to those present in the Schinzel acrocallosal syndrome. The similarity with the Greig syndrome is discussed and the question is raised whether both syndromes are variant examples of the same autosomal dominant condition.     

Treacher Collins syndrome—an example of a craniofacial development defect

Treacher Collins syndrome is an autosomal dominant disorder of craniofacial development the features of which include conductive hearing loss and cleft palate; diagnosis is complicated by marked variability in expression. Whilst the underlying genetic defect is unknown it is thought to be due to an abnormality of neural crest cell migration. The mutated gene has been mapped to chromosome 5q32-33.1, a high resolution genetic and radiation hybrid map surrounding the locus created, and flanking markers identified. The critical region has subsequently been cloned in yeast artificial chromosome and attempts to isolate the mutated gene are in progress.     

Presumptive long arm deletion of chromosome 8: a new syndrome?

Summary This communication describes an infant with growth and psychomotor retardation and severe congenital malformations, who was found to have an interstitial deletion of the long arm of chromosome 8: 46,XY,del(8) (q13q22). Comparison with the only other previously reported patient with a deletion of a similar chromosomal segment suggested that deletion of the long arm of chromosome 8 may constitute a clinically recognizable syndrome.     

Sweet's syndrome – a comprehensive review of an acute febrile neutrophilic dermatosis

Sweet's syndrome (the eponym for acute febrile neutrophilic dermatosis) is characterized by a constellation of clinical symptoms, physical features, and pathologic findings which include fever, neutrophilia, tender erythematous skin lesions (papules, nodules, and plaques), and a diffuse infiltrate consisting predominantly of mature neutrophils that are typically located in the upper dermis. Several hundreds cases of Sweet's syndrome have been published. Sweet's syndrome presents in three clinical settings: classical (or idiopathic), malignancy-associated, and drug-induced. Classical Sweet's syndrome (CSS) usually presents in women between the age of 30 to 50 years, it is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy. Approximately one-third of patients with CSS experience recurrence of the dermatosis. The malignancy-associated Sweet's syndrome (MASS) can occur as a paraneoplastic syndrome in patients with an established cancer or individuals whose Sweet's syndrome-related hematologic dyscrasia or solid tumor was previously undiscovered; MASS is most commonly related to acute myelogenous leukemia. The dermatosis can precede, follow, or appear concurrent with the diagnosis of the patient's cancer. Hence, MASS can be the cutaneous harbinger of either an undiagnosed visceral malignancy in a previously cancer-free individual or an unsuspected cancer recurrence in an oncology patient. Drug-induced Sweet's syndrome (DISS) most commonly occurs in patients who have been treated with granulocyte-colony stimulating factor, however, other medications may also be associated with DISS. The pathogenesis of Sweet's syndrome may be multifactorial and still remains to be definitively established. Clinical and laboratory evidence suggests that cytokines have an etiologic role. Systemic corticosteroids are the therapeutic gold standard for Sweet's syndrome. After initiation of treatment with systemic corticosteroids, there is a prompt response consisting of dramatic improvement of both the dermatosis-related symptoms and skin lesions. Topical application of high potency corticosteroids or intralesional corticosteroids may be efficacious for treating localized lesions. Other first-line oral systemic agents are potassium iodide and colchicine. Second-line oral systemic agents include indomethacin, clofazimine, cyclosporine, and dapsone. The symptoms and lesions of Sweet's syndrome may resolved spontaneously, without any therapeutic intervention; however, recurrence may follow either spontaneous remission or therapy-induced clinical resolution.     

Down's syndrome,Edwards' syndrome,Patau's syndrome —synthesis of glycosaminoglycans

Synthesis of glycosaminoglycans (GAGS) by fibroblasts derived from seven patients with Down's syndrome, five patients with Edwards' syndrome, and two patients with Patau's syndrome were studied in cell culture. The aneuploid strains were compared with diploid fibroblasts from age-matched controls. In terms of hyaluronic acid and sulfated GAG synthesis, the amount of synthesized hyaluronic acid was not significantly different between postnatal aneuploid strains and controls.     

Cytogenetic mapping of a novel locus for type II Waardenburg syndrome

An Italian family in which Waardenburg syndrome type II (WS2) segregates together with a der(8) chromosome from a (4p;8p) balanced translocation was studied. Cytogenetic analysis by painting and subtelomeric probe hybridization positioned the chromosome 8 breakpoint at p22-pter. Fluorescence in situ hybridization analysis with yeast artificial chromosomes from a contig spanning the 8p21-pter region refined the breakpoint in an interval of less than 170 kb between markers WI-3823 and D8S1819. The only cloned gene for WS2 is that for microphtalmia (MITF) on chromosome 3p. In this family, MITF mutations were excluded by sequencing the whole coding region. The 8p23 region may represent a third locus for WS2 (WS2C).     

Haematemesis: a new syndrome?

Three patients presented with symptoms suggesting a Mallory-Weiss tear. Endoscopy showed a localized, clearly demarcated area of bright red mucosa near the gastro-oesophageal junction; this was thought to have arisen by retrograde intussusception of the stomach during vomiting or retching and may have caused the haemorrhage.     

Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome

Birt-Hogg-Dubé syndrome (BHD), a genodermatosis characterized by multiple hamartomas of the hair follicle (fibrofolliculoma), predisposes individuals to an increased risk of developing renal neoplasms and spontaneous pneumothorax. Previously, we localized the BHD locus (also known as FLCN) to chromosome 17p11.2 by linkage analysis and subsequently identified germline mutations in a novel gene in probands from eight of the nine families with BHD in our screening panel. Affected members of five of the families inherited an insertion/deletion of a cytosine in a C8 tract in exon 11. This mutation was also identified by exon 11 screening in probands from 22 of 52 additional families with BHD and therefore represents a hypermutable "hotspot" for mutation in BHD. Here, we screened the remaining 30 families from this large BHD cohort by direct sequence analysis and identified germline BHD mutations in 84% (51/61) of all families with BHD recruited to our study. Mutations were located along the entire length of the coding region, including 16 insertion/deletion, 3 nonsense, and 3 splice-site mutations. The majority of BHD mutations were predicted to truncate the BHD protein, folliculin. Among patients with a mutation in the exon 11 hotspot, significantly fewer renal tumors were observed in patients with the C-deletion than those with the C-insertion mutation. Coding-sequence mutations were not found, however, in probands from two large families with BHD whose affected members shared their family's BHD-affected haplotype. Of the 53 families with BHD whose members inherited either a germline mutation or the affected haplotype, 24 (45%) had at least one member with renal neoplasms. Three families classified with familial renal oncocytoma were identified with BHD mutations, which represents the first disease gene associated with this rare form of renal neoplasm. This study expands the BHD-mutation spectrum and evaluates genotype-phenotype correlations among families with BHD.     

Guillain-Barré syndrome as a cause of acute flaccid paralysis in Iraqi children: a result of 15 years of nation-wide study

Background

Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis (AFP) in the post-poliomyelitis eradication era. This is the first study done to identify the epidemiology, clinical features, and outcome of GBS in Iraqi children over 15 years.

Methods

The surveillance database about AFP cases?<?15 years reported during January 1997-December 2011 was used.

Results

GBS represented 52.5% of AFP cases, with an incidence of 1.33 case/100,000 population?<?15 years/year. There was a higher incidence in the Southern provinces, age group 1–4 years, males, and outside the capital city of province, with no significant seasonal variations (p?=?.22). Survival probability after the 1 year of onset for those with respiratory muscle involvement was .76 (95% CI: .60-.86), versus .97 (95% Cl: .96-.98) for those who did not develop it (p?<?.001); and .97 (95% CI: .96-.98) for those living inside the capital city, versus .94 (.93-.95) for those living outside (p?=?.001). Cumulative incidence of residual paralysis for patients living inside the capital city was .21 (95% CI: .18-.24), versus .27 (95% CI: .25-.29) for those living outside (p?<?.001).

Conclusions

The incidence, age and gender distribution, and seasonality of GBS among Iraqi children is similar to those reported from other previous studies. It is the most important cause of AFP, especially in those between the age of 1 to 4 years living in rural areas.

     

Congenital blepharophimosis and ptosis in a mentally retarded girl: a new case of Ohdo syndrome?

A mentally retarded girl with congenital blepharophimosis, ptosis, abnormal teeth and other features consistent with Ohdo syndrome is reported.     

Wiskott–Aldrich syndrome: a gene,a multifunctional protein and the beginnings of an explanation

Patients with Wiskott–Aldrich syndrome show various defects in the normal function of platelets and lymphocytes. The recent identification of the gene responsible for this syndrome has led to a surge of studies aimed at solving the puzzle posed by the varied phenotype observed in this disease. It is now known that WASP, the protein product of this gene, can interact with a large number of other proteins known to be involved in the regulation of signal transduction and cytoskeletal organization. Thus, WASP appears to integrate these two basic and fundamental cellular mechanisms. Several groups are now focusing on understanding the function of WASP in detail, and translating this new knowledge into improved therapies.     

Hypoalbuminaemic hyponatraemia: a new syndrome?

Six patients with severe hyponatraemia had neurological features of hyponatraemia and pronounced hypoalbuminaemia. All had biochemical features typical of the syndrome of inappropriate secretion of antidiuretic hormone with low serum osmolality and an inappropriately high urinary osmolality. All were given infusions of whole plasma or albumin solution, or both, to restore their plasma albumin concentrations to normal, which led to a dramatic increase in plasma sodium concentrations and serum osmolality, with a concomitant fall in urinary osmolality in all patients. Neurological features were reversed in four patients. It is suggested that severe hypoalbuminaemia is an important cause of appreciable hyponatraemia; infusions of plasma and albumin in such patients may reverse the biochemical and clinical features and should form the basis of management.