Two missense mutations in SALL4 in a patient with microphthalmia, coloboma, and optic nerve hypoplasia.

To investigate the genetic etiology of anophthalmia and microphthalmia, we used exome sequencing in a Caucasian female with unilateral microphthalmia and coloboma, bilateral optic nerve hypoplasia, ventricular and atrial septal defects, and growth delays. We found two sequence variants in SALL4 - c.[575C>A], predicting p.(Ala192Glu), that was paternally inherited, and c.[2053G>C], predicting p.(Asp685His), that was maternally inherited. Haploinsufficiency for SALL4 due to nonsense or frameshift mutations has been associated with acro-renal ocular syndrome that is characterized by eye defects including Duane anomaly and coloboma, in addition to radial ray malformations and renal abnormalities. Our report is the first description of structural eye defects associated with two missense variants in SALL4 inherited in trans; the absence of reported findings in both parents suggests that both sequence variants are hypomorphic mutations and that both are needed for the ocular phenotype. SALL4 is expressed in the developing lens and regulates BMP4, leading us to speculate that altered BMP4 expression was responsible for the eye defects, but we could not demonstrate altered BMP4 expression in vitro after using small interfering RNAs (siRNAs) to reduce SALL4 expression. We conclude that SALL4 hypomorphic variants may influence eye development.

MACRODYSTROPHIA LIPOMATOSA WITH ULNAR DISTRIBUTION IN HAND: MR EVALUATION OF A RARE DISORDER.

Macrodystrophia lipomatosa is a rare, non-hereditary congenital anomaly characterized by localised gigantism in the form of macrodactyly affecting a part of limb and rarely entire limb due to overgrowth of all mesenchymal elements. Radiological and pathological hallmark is the disproportionate fibroadipose tissue proliferation in subcutaneous tissue, nerve sheaths, and periosteum that lead to soft tissue and bony enlargement. We present the case of a twenty years old female who presented with history of gradual enlargement of the medial aspect of right hand along ulnar nerve distribution since birth. MRI showed hypertrophy of bones and soft tissue with fatty proliferation, leading to the diagnosis of macrodystrophia lipomatosa.

Exome sequencing in 32 patients with anophthalmia/microphthalmia and developmental eye defects.

Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.(Gln91His), RARB, p.Arg387Cys and GDF6, p.Ala249Glu) and inherited mutations in STRA6 in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a de novo COL4A1 mutation, p.(Gly773Arg), expanding the phenotype associated with COL4A1 to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two PNPT1 mutations, p.(Ala507Ser) and c.401-1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the PNPT1 and COL4A1-associated disorders described here.

Necrotizing colitis complicating necrotized pancreatitis: look out for intestinal pneumatosis.

Acute pancreatitis is a common cause of acute abdominal pain and is associated with a wide variety of complications. Pancreatic necrosis is one of the most important complications and is considered to be the most important indicator of disease severity as the increased frequency of death in acute pancreatitis is directly correlated with the development and extent of pancreatic necrosis. In addition to pancreatic necrosis, wide spectrums of colonic complications have been described, including functional and mechanical ileus, ischemic necrosis and fistula formation. In acute pancreatitis bowel ischemia usually involves the transverse colon or the hepatic and splenic flexures and may range in severity from mild superficial mural involvement to transmural colonic necrosis.This article reports a case of large bowel infarction as a complication of severe necrotizing pancreatitis in a 35-year-old male patient.

Clinics in diagnostic imaging (130). Congenital megalourethra.

A 35-day-old boy presented with complaints of an enlarged deformed penis and a history of difficulty in micturition. Haematological and biochemical analyses as well as renal tract sonography were normal. Retrograde urethrography revealed congenital megalourethra which was confirmed on cystourethroscopy. The literature pertaining to the types, aetiology, associated abnormalities, differential diagnosis, imaging and management of megalourethra is discussed.

Evaluating the appropriateness of thromboprophylaxis in an acute care setting using a computerised reminder, through order-entry system.

AIMS: Evidence suggests that thromboprophylaxis is still significantly underutilised across the United States despite its relationship with morbidity, mortality and resource expenditure. Previous randomised trials that have incorporated computerised reminders, through order-entry systems, have resulted in increased rates of thromboprophylaxis and lower incidences of clinically diagnosed deep-vein thrombosis or pulmonary embolism. The primary purpose of this prospective, observational study is to evaluate the use and appropriateness of preset computerized thromboprophylaxis regimens for patients in a major county metropolitan hospital over a 1-month period by evaluating the proportion of patients actually receiving recommended thromboprophylaxis according to established hospital guidelines. METHODS: This prospective, observational study was conducted in a large county hospital that recently established an evidence-based routine computerised policy to decrease risk of venous thromboembolism. Physicians, residents, medical interns, medical students, pharmacy students, and nurses were the targets of the investigation. Data were randomly collected between 10 internal medicine teams from 10 October 2006 to 10 November 2006. Investigators completed one DVT/PE risk assessment form for each patient reviewed and compared this to actual prescribed therapy to determine appropriateness of therapy. RESULTS: Pharmacological or non-pharmacological thromboprophylaxis was administered to 100% of patients evaluated. Eighty-six patients received recommended DVT/PE prophylaxis based on established hospital guidelines. DISCUSSION: Reported values seem to indicate that computerized reminders are capable of providing venous thromboprophylaxis for medically ill (non-surgical) patients relative to published norms. CONCLUSION: Results of this observational study reinforces the evidence that computerized, reminders, through order-entry systems might increase the delivery of thromboprophylaxis for hospitalized patients.