Genetic and physical mapping of the McKusick-Kaufman syndrome

McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos. This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity. Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978. The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons. Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894 , an area that includes the Alagille syndrome critical region. The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The physical map of this region has been defined, and additional polymorphic markers have been isolated. The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille syndrome. Sequencing of jagged1 in two unrelated individuals affected with McKusick-Kaufman syndrome has not revealed any disease- causing mutations.      

Analysis of the dynamic mutation in the SCA7 gene shows marked parental effects on CAG repeat transmission

The gene for spinocerebellar ataxia 7 (SCA7) includes a transcribed, translated CAG tract that is expanded in SCA7 patients. We have determined expansions in 73 individuals from 17 SCA7 kindreds and compared them with repeat lengths of 180 unaffected individuals. Subjects with abnormal expansions comprise 59 clinically affected individuals and 14 at-risk currently unaffected individuals predicted to carry the mutation by haplotype analysis. For expanded alleles, CAG repeat length correlates with disease progression and severity and correlates inversely with age of onset. Increased repeat lengths are seen in generational transmission of the disease allele, consistent with the pattern of clinical anticipation seen in these kindreds. Repeat lengths in expanded alleles show somatic mosaicism in leukocyte DNA, suggesting that these alleles are unstable within individuals as well as between generations. Although dynamic repeat expansions from paternal transmissions are greater than those from maternal transmissions, maternal transmission of disease is more common, suggesting germline or embryonic effects of the repeat expansion.      

Incidental Non-Inguinals Hernias in Totally Extra-Peritoneal Hernia Repair

Introduction

Totally extra-peritoneal (TEP) inguinal hernia repair allows identification and repair of incidental non-inguinal groin hernias. We assessed the prevalence of incidental hernias during TEP inguinal hernia repair and identified the risk factors for incidental hernias.

Materials and Methods

Consecutive patients undergoing TEP repair from May 2005 to November 2012 were the study cohort. Inspection for ipsilateral femoral, obturator and rarer varieties of hernia was undertaken during TEP repair. Patient characteristics and operative findings were recorded on a prospectively collected database.

Results

A total of 1,532 TEP repairs were undertaken in 1,196 patients. Ninety-three patients were excluded due to incomplete data, leaving 1,103 patients and 1,404 hernias for analyses (1,380 male; 802 unilateral and 301 bilateral repairs; median age, 59 years). Among the 37 incidental hernias identified (2.6% of cases), the most common type of incidental hernia was femoral (n=32, 2.3%) followed by obturator (n=2, 0.1%). Increasing age was associated with an increased risk of incidental hernia, with a significant linear trend (p<0.01). The risk for patients >60 years of age was 4.0% vs 1.4% for those aged <60 years (p<0.01). Incidental hernias were found in 29.2% of females vs 2.2% of males, (p<0.0001). Risk of incidental hernia in those with a recurrent inguinal hernia was 3.0% vs 2.6% for primary repair (p=0.79).

Conclusions

Incidental hernias during TEP inguinal hernia repair were found in 2.6% of cases and, though infrequent, could cause complications if left untreated. The risk of incidental hernia increased with age and was significantly higher in patients aged >60 years and in females.     

Dust mite allergens: ecology and distribution

The most important allergy-causing mites found in homes worldwide are the house dust mites Dermatophagoides farinae, D. pteronyssinus, Euroglyphus maynei, and the storage mite Blomia tropicalis. Most homes contain multiple species. The most prevalent mite species and allergen in homes differ geographically, between homes within a geographical region, and among areas within a home. Therefore, it is important to know which mite species are present in a geographical area when performing diagnostic testing and prescribing immunotherapy. The key factor that influences mite survival and prevalence is relative humidity. Mites are present in homes in humid geographical areas and are rare or absent in drier climates unless humidity is artificially raised. Generally speaking, dust mite allergen levels are low in public buildings and transportation compared to levels in homes.     

Cluster headache-like headache, Hageman trait deficiency, retrobulbar neuritis, and giant aneurysm

A 56-year-old, previously reported woman with cluster headache-like headache with bouts of unilateral (the side of predominance changing through the years) severe headache had a familial history (three generations) of partial Hageman factor deficiency and bleeding episodes. A giant aneurysm was found to be lodged in the anterior communicating artery on the left side. Clinically, the features were atypical for cluster headache: onset at a young age (14 years), episodes of retrobulbar neuritis appearing at the side of pain, etc. Studies of forehead sweating indicated that the right side was the pathologic one, from an autonomic point of view, as did pupillometric studies. However, during attacks, which were left-sided at the time, forehead sweating was marked laterally on the left side and on the upper eyelid, but not on the right. The "signal" usually reaching the autonomically stigmatized side during attacks of cluster headache, therefore, did not seem to reach the sweat glands on that (the right) side during the attack in the present case. This headache may, therefore, be distinct from cluster headache, both from a clinical and from an autonomic function point of view.