Stickler syndrome - lessons from a national cohort.

In 2011 NHS England commissioned a new national specialist MDT service for patients and families affected by Stickler syndrome. The Stickler syndromes form part of the spectrum of inherited vitreoretinopathies and are the most common cause of retinal detachment in childhood and the most common cause of familial retinal detachment. Now in its 10th year, the Stickler Highly Specialised Service (HSS) has assessed 1673 patients from 785 families. Using a combination of accurate phenotyping and molecular genetic analysis it is possible to identify the underlying genetic mutation in over 95% of cases including those with deep intronic mutations likely to be missed by conventional exome panel analysis and which require whole gene sequencing and supplementary functional analysis to confirm pathogenicity. The vast majority that presents to ophthalmologists will be from one of three autosomal dominant sub-groups with a high associated risk of retinal detachment but the diagnosis is often overlooked, especially in adults. In contrast to many other blinding retinal conditions, blindness through giant retinal tear detachment particularly in children is largely preventable provided these high-risk groups are identified and appropriate evidence-based prophylaxis offered. This article summarises ten selected briefcase histories from the national dataset with key learning points from each.

Treatment compliance among prenatal care patients with substance abuse problems.

There is an insufficient number of substance abuse treatment programs available to pregnant women; however, even when women do enroll in treatment, they often choose not to comply with particular components of their treatment. To better understand what factors are associated with a woman's likelihood of compliance with treatment, this study assesses 244 pregnant, substance-using women enrolled in a specialized substance abuse treatment program. Women who complied with treatment referrals are compared with those who did not comply with referrals on various factors including their sociodemographic characteristics, types of substance use before and during pregnancy, experiences of violence before and during pregnancy, and prior substance use treatment. Bivariate analysis found that outpatient treatment compliance was more likely among women who smoked cigarettes before pregnancy, women who had received previous substance abuse treatment, and women whose partner had received previous substance abuse treatment. Outpatient treatment compliance did not vary by sociodemographic characteristics, any other type of substance use, or the women's experiences of violence. Inpatient treatment compliance was more likely among women who received prior substance abuse treatment; however, no other characteristic was found to be associated with inpatient treatment compliance. Logistic regression analyses, which controlled for various factors, suggested that past experiences with substance abuse treatment by the woman or her partner were significantly associated with treatment referral compliance. These findings suggest that the previous treatment experiences of women and their partners are important factors in shaping a successful substance abuse treatment program for pregnant women.

Bias and limits of agreement between hydrodensitometry, bioelectrical impedance and skinfold calipers measures of percentage body fat.

Previous research has often used correlations as a statistical method to show agreement; however, this is not a valid use of the statistic. The purpose of this study was to investigate the bias and limits of agreement for three methods of estimating percentage body fat for 117 male and 114 female university athletes: hydrodensitometry (HYD), bioelectrical impedance (BIA) and skinfold calipers (SKF). The mean (SD) percentage body fat for males as assessed by HYD, BIA and SKF methods, respectively, were 13.2 (3.3)%, 14.1, (3.3)% and 13.0 (3.2)%. Female body fat measurements were 22.5 (3.9)%, 23.7 (4.3)% and 23.8 (4.2)%, respectively. Pearson product moment correlations for male and female body fat percentages between the three methods were high, ranging from 0.81 to 0.86 (P < 0.05). However, compared to the criterion measure of body fat percentage (HYD), the magnitude of agreement BIA and SKF revealed a different pattern. The mean absolute difference between HYD and BIA measurements of body fat for males was -0.8 (2.0)% fat, and between HYD and SKF was it was 0.2 (1.7)% fat. The mean absolute difference for females between HYD and BIA was -1.2 (2.5)%; for HYD and SKF it was -1.4 (2.2)%. Compared to the HYD measures for males and females, the BIA and SKF measures were as much as a 3.8% underestimation and a 6.2% overestimation of body fat. This study provides evidence that the strength of a correlation does not indicate agreement between two methods. In future, reliability and validity studies should examine the absolute differences between two variables and calculate limits of agreement around which a practitioner can appreciate the precision of the methodologies.

Gymnasts, distance runners, anorexics body composition and menstrual status.

Ten top class female distance runners, ten female anorexics and twenty female gymnasts of a similar age were compared for height, mass, %fat, fat mass, lean body mass, age of menarche and incidence of amenorrhoea. The mean age of the distance runners, anorexics, and gymnasts was 13.6 years, 14.7 years, and 13.3 years respectively. In comparison to normal data on females of a similar age they were shorter, lighter, had lower fat masses, and %fat, and the gymnasts and anorexics had lower lean body masses. However, the gymnasts and runners had higher lean body masses compared with the anorexic group. There were no significant differences in body composition by hydrostatic weighing but of these three groups the anorexics tended to have the highest total skinfold, %fat and fat masses. Only 20% of the gymnasts, 40% of the runners and 70% of the anorexics had started menstruating compared with 95% of girls of a similar age. Of the girls in our study who had started menstruating one gymnast, (25% of sub-group) two runners (50% of sub-group) and seven anorexics (100% of sub-group) had developed secondary amenorrhoea. The low body masses, low fat masses, delayed menarche and secondary amenorrhoea in athletes are discussed in relation to low caloric intake, stress, hormone levels, high training loads and genetic factors. Our data demonstrating no significant differences in body composition variables between the three groups of young girls, support the main contention that this type of physique may arise through different mechanisms leading to a common outcome, but without a proven causal link between anorexia and athletic performance.

Renal failure due to BK virus infection in an immunodeficient child.

We report a child with cartilage-hair hypoplasia and Hodgkin's disease who developed progressive renal failure and died following infection with a polyomavirus, BK virus. Renal biopsy showed interstitial inflammation, tubular atrophy, and intranuclear inclusions in tubular epithelium, with large numbers of papovavirus particles within the cells. BK virus infection was confirmed by polymerase chain reaction on renal biopsy material and in urine and the demonstration of a high titre of haemagglutination inhibition (HI) and IgM antibody to the virus in the patient's serum. This case emphasises the need to study in depth any unusual clinical manifestation in immunocompromised patients to delineate better the full clinical impact of less well-established pathogens such as BK virus.

Anthropometric and somatotype variables related to strength in American football players.

The purpose of this study was to investigate the differences in somatotype, % fat, and strength in relation to body mass of two groups of American football players. One hundred and forty-three football players (85 high school and 58 college) were classified into five weight groups (< 73 kg, 73-82 kg, 83-91 kg, 91-100 kg, > 100 kg). Body composition was estimated from skinfold, and somatotype was determined using the Heath-Carter method. Strength was measured from one-repetition maximum (1-RM) lifts in the bench press and deadlift. Most of the somatotypes were dominant mesomorphs for the high school player and endomesomorphs for the college player. The weight groups in both the high school and college footballer showed significant differences in % fat, somatotype, and strength measures between the lower and higher weight categories. Weight was a greater factor dictating strength in either lift in the high school player than in the college player. A higher mesomorphic component was a more important factor determining strength in the college player while a lower ectomorphic component contributed more in the high school player. The proportion of the variance accounted for by regression equations for the bench press and deadlift was 17% to 41% in the high school player and 35% to 61% in the college player. Although football requires a large individual at certain positions, the question remains concerning overall size versus muscularity to achieve a superior performance level.

Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease.

We report the necropsy findings for three infants with the unusual combination of proximal renal tubular dysgenesis and severe congenital liver disease with excessive iron in several organs resembling neonatal hemochromatosis. Two of the infants were caucasian siblings and one was an Australian aborigine. One died in utero at 35 weeks of gestation and two died at 7 days. The liveborn infants presented with anuria and liver failure. The livers all showed marked loss of hepatocytes and replacement by pseudotubules in the collapsed lobules. The liveborn infants also showed giant cell transformation of hepatocytes, small regenerative nodules, cholestasis, and normal bile ducts. Absence of proximal renal convolutions was confirmed by epithelial membrane antigen positivity in nearly all tubules. In each family there was another sibling with congenital liver disease, fatal in one case, but no renal tubular dysgenesis. No infection or metabolic disease was uncovered in any of our patients, and the cause of the hepatocyte destruction was not determined. The combination in three infants of two rare congenital diseases could be genetic or acquired in utero from the same etiological agent. Alternatively, the absence of proximal convolutions could be secondary to hypoperfusion, perhaps because of shock due to extensive necrosis of hepatocytes.

Subdermal fibrous hamartoma of infancy: pathology of 40 cases and differential diagnosis.

Forty subdermal fibrous hamartomas of infancy occurred in 29 males and 11 females who were 7 months to 4 years of age at surgery. At least 4 were congenital. The lesions were situated in axilla, chest wall, and breast (17 cases); abdominal wall, inguinal region, and scrotum (8); buttock and lower limb (6); upper limb (4); neck and scalp (3); and low back (2). They were 0.7 to 10 cm, ill defined, and five underwent reexcision, which was curative in all. All had the characteristic mixture of fibrous and adipose tissue and nests of immature mesenchyme in different proportions, and nearly all showed lymphocytes and thick patent capillaries in the mesenchyme. However, the fibrous component varied considerably in amount, pattern, and cellularity, so that lesions that were typical in some areas, in others resembled collagenizing vascular granulation tissue, deep fibrous histiocytoma, or fibromatosis. Those in which adipose tissue predominated were distinguished from fibrolipoma by foci of immature mesenchyme and from lipoblastoma by their lack of a capsule and of a lobular pattern.

Pathology of osseous and genitourinary lesions of Proteus syndrome.

A male patient followed from the age of 3 to 25 years was eventually diagnosed as having Proteus syndrome. He was born with linear epidermal nevi of the neck and forearm and presented with macrodactyly of the right hand and progressive hemihypertrophy of the right lower limb recurring after multiple reduction operations. The bone ends showed disorderly overgrowth of hyaline and fibrocartilage mixed with collagen and bone, and early differential diagnoses included Ollier's disease. The child also had vertebral anomalies, scoliosis, a bony protrusion of the cranial vertex, and strabismus. In the second decade he developed gyriform swelling of the soles, retinopathy, bilateral papillary cysts of the epididymis, and a giant cyst of the left kidney with complex glandular foci. At 22 years a 3-cm meningioma containing adipose tissue was resected, and at 24 years a 3-cm cellular nodule of the rete testis with hyperchromatic foci, probably an adenoma, was removed. The features of Proteus syndrome were those of hyperplasia and neoplasia of mostly mesodermal tissues. Unlike other reported cases, overgrowth of a finger recurred at 25 years.

Maldescent of the thymus: 34 necropsy and 10 surgical cases, including 7 thymuses medial to the mandible.

Among 3236 pediatric necropsies over 23 years, abnormal position of thymic tissue was recorded in 34 cases. Cardiac anomalies, predominantly those seen in DiGeorge syndrome, were present in 24; 3 had noncardiac anomalies only, 4 had other diseases, and 3 were sudden infant deaths. Mediastinal thymic tissue was absent in 22 cases, small or unilateral in 7, and normal in 5. The maldescended thymic tissue was unilateral in 18, bilateral in 11, and multiple on one or both sides in 5. It was situated near the thyroid gland in 19, lower in the neck in 6, and higher in 9, including 7 medial to the submandibular salivary gland and 1 at the base of the skull. The maldescended tissue approached the size of a normal lobe of thymus in eight and was 2.4 to 0.1 cm in the remainder. Over the same period, in only two cases was no thymic tissue found. Among 68,000 surgical specimens over 40 years, there were 10 cases of ectopic thymus in the neck, including 1 cutaneous and 4 cystic. This frequency of thymic tissue in the neck may explain why lymphoid tissues are sometimes relatively normal in cases of absent mediastinal thymus and behooves a search in the submandibular salivary gland region and higher before diagnosing thymic agenesis.

Biological and performance variables in relation to age in male and female adolescent athletes.

To observe the cross-sectional nature of the effect of age, height, and body mass on motor performance during adolescence (13-18 years), 103 boy and 65 girl athletes were measured for motor performance and anthropometric variables. Motor performances included tests of strength, muscular endurance, flexibility, aerobic capacity, anaerobic power, speed, and agility. Anthropometric determinations included height, body mass, lean body mass, %fat, and somatotype. Boys were significantly different from girls in all measurements except endomorphy, while girls were significantly superior to boys only in flexibility. Physical maturation, as reflected by height and body mass, was a major contributor to increases in motor performance. Somatotype did not differ greatly across the age groups. Boys were significantly more mesomorphic than girls, while girls were significantly more ectomorphic than boys. Higher %fat and more endomorphy were significantly related to poorer performance for relative aerobic capacity, 40-yd dash, and agility in boys but only for upper body muscular endurance in girls. Mesomorphy had higher relationships with performance variables among boys than among girls. Growth would appear to contribute significantly to enhanced motor performance with age, and its effect may be different in boys than in girls.

Rare malignant mid-femoral tumours in the first decade of life. Report of three cases with short literature review.

The most common femoral shaft tumours in children are eosinophilic granuloma and Ewing's sarcoma. Three children in the first decade of life with rare femoral shaft tumours are reported. There was one osteosarcoma and two chondrosarcomas. Radiographic differential diagnosis of the femoral shaft tumours and microscopic diagnostic difficulties of chondrosarcoma are discussed.

Male pseudohermaphroditism in XY children with female phenotype.

Twenty-two children with female external genitalia, testes, and 46,XY karyotype, most presenting with inguinal lumps or hernias, underwent bilateral gonadal excision (21 patients) or biopsy. On clinical and biochemical grounds, 13 were classed as androgen resistance (AR), 6 as testosterone biosynthetic defect, 2 as XY gonadal dysgenesis, and 1 as 5 alpha-reductase deficiency. The main pathological difference between the groups was that in AR the gonocytes were present in normal numbers, whereas in testosterone biosynthetic defect, gonocytes, though present in infancy, were rare or absent by 12 years. In all groups, Leydig cells, normally not recognizable between 1 year and puberty, were often present and could not always be attributed to a gonadotropin stimulation test. In four cases the tubules were more heterogeneous than those seen in control testes, but tubular atrophy and increased stroma were indistinguishable from those in age-matched cryptorchid controls. Small Sertoli cell nodules were found in three children, but no carcinoma in situ was identified. The epididymis, said to be absent in adult cases of AR, was consistently present but often cystic or atrophic. Oviduct-like structures were found in three cases of AR, and smooth muscle resembling round ligament in four. Because of the difficulty in distinguishing the types of male pseudohermaphroditism microscopically, we recommend that XY female children should undergo thorough endocrinologic investigation before orchidectomy.

A comprehensive microcomputer network program for histopathology.

For a small hospital with a limited budget, a stand-alone histopathology microcomputer network may be more valuable to the pathologist than one running off the hospital's main computer. In return for sacrificing the limited benefit of screen reading of pathology reports in the wards, one receives the great advantage of more rapid retrieval of disease data. Commercial relational database programs for microcomputers can now achieve nearly all the power of a minicomputer program, with more versatility. Using an application developed on such software, we now have 30,000 pathology reports entered, from which we can retrieve a list of pathology numbers, with patients' names, age, sex, disease, and site, for any diagnosis in 3-5 seconds. The application includes full biopsy reports for doctors and wards, autopsy final diagnoses, computer-assisted Snomed coding, outside consultations, literature abstracts, daybook printing, workload statistics and billing codes and charges, and a cytology module has been added for another hospital. Moreover, the interested pathologist can easily make his own alterations to menus, entry screens, fields, and screen listing or printout formats.