In this report, we describe three unrelated children with an apparently novel bone fragility disorder that is associated with an idiopathic mineralization defect. Recurrent lower limb fractures started with weight bearing. The patients had none of the phenotypic, radiological, or histomorphometric features classically associated with known bone fragility disorders such as osteogenesis imperfecta (OI), idiopathic juvenile osteoporosis (IJO), or mild autosomal dominant osteopetrosis. Radiologically, there was increased metaphyseal trabeculation, normal to increased cortical thickness, and no evidence of rickets or osteomalacia. Areal and volumetric bone mineral density (BMD) of the lumbar spine did not show any major alteration. Peripheral quantitative computed tomography of the radius showed elevated cortical thickness and total and trabecular volumetric bone mineral density in one patient. Qualitative histology of iliac bone biopsy specimens showed a paucity of the birefringent pattern of normal lamellar bone. Quantitative histomorphometric analysis demonstrated osteomalacia with a prolonged mineralization lag time in the presence of a decreased mineral apposition rate. There was no biochemical evidence of abnormal calcium or phosphate metabolism. Type I collagen mutation analysis was negative. We conclude that this is a bone fragility disorder of moderate severity that tends to cause fractures in the lower extremities and is associated with the accumulation of osteoid due to an intrinsic mineralization defect. The pathogenetic basis for this disorder remains to be elucidated.

The pregnancies of two women with osteogenesis imperfecta who received intravenous pamidronate before conception are reported. The mothers suffered no ill effects. One baby had transient asymptomatic hypocalcemia and one had bilateral talipes equinovarus.

Leri-Weill syndrome (LWS) is a skeletal dysplasia with mesomelic short stature, bilateral Madelung deformity (BMD) and SHOX (short stature homeobox-containing gene) haploinsufficiency. The effect of 24 months of recombinant human growth hormone (rhGH) therapy on the stature and BMD of two females with SHOX haploinsufficiency (demonstrated by fluorescence in situ hybridisation) and LWS was evaluated. Both patients demonstrated an increase in height standard deviation score (SDS) and height velocity SDS over the 24 months of therapy. Patient 1 demonstrated a relative increase in arm-span and upper segment measurements with rhGH while patient 2 demonstrated a relative increase in lower limb length. There was appropriate advancement of bone age, no adverse events and no significant deterioration in BMD. In this study, 24 months of rhGH was a safe and effective therapy for the disproportionate short stature of SHOX haploinsufficiency, with no clinical deterioration of BMD.

This study was designed to determine the intrafamilial effect of SHOX haploinsufficiency on stature, by comparing the growth and phenotype of 26 SHOX haploinsufficient individuals with 45 relatives and population standards. It confirmed that SHOX haploinsufficiency leads to growth restriction from birth to final height. Compared to unaffected siblings, the SHOX haploinsufficient cohort was 2.14 SDS (3.8 cm) shorter at birth and 2.1 SDS shorter through childhood. At final height females were 2.4 SDS (14.4 cm) shorter and males 0.8 SDS (5.3 cm) shorter than normal siblings. The family height analysis suggests that the effect of SHOX haploinsufficiency on growth may have been previously underestimated at birth and overestimated in males at final height. SHOX haploinsufficiency leads to short arms in 92%, bilateral Madelung deformity in 73% and short stature in 54%. Females were more severely affected than males. We conclude that SHOX is a major growth gene and that mutations are associated with a broad range of phenotype.

In 1878, Madelung described a painful, disabling, and deforming abnormality of the forearm in which misalignment of the bones of the wrist and forearm resulted in a “spontaneous forward subluxation of the wrist”.1 A familial form of a bilateral wrist deformity resulting from dorsal dislocation of the ulnar head, accompanied by mesomelic short stature was first reported in 1929 and later termed Leri-Weill dyschondrosteosis (LWD).2–4 In LWD, the Madelung deformity results from dysplasia located at the medial aspect of the distal radial growth plate, where narrowing and premature fusion of the physis occurs.5 This dysplasia leads to differential growth rates between the lesion and the distal lateral radial physis impeding growth and pulling the lateral radial epiphysis off line as the remaining physis advances.6 In its fully developed form, Madelung deformity leads to shortening and bowing (sometimes marked) of the radius and the involvement of other epiphyses in this disorder results in mesomelia.7 Typically, Madelung deformity does not appear until mid-childhood but is usually preceded by radiological signs.8 Other localised lesions in the ulnar-palmar zone of the distal radius can result in differential growth rates leading to Madelung deformity including Turner, Olliers, and multiple exostoses syndromes and environmental causes.3,4,9 ### Key points

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome first described by Beckwith in 1963.1 The incidence of BWS is about 1:13 700 births, with an equal sex distribution.2 It is a clinically and genetically heterogeneous disorder. Table 1 outlines the major clinical features. The existence of milder forms of BWS probably underestimates this incidence.1 Developmental delay in BWS has been associated with chromosomal duplication, prematurity, and hypoglycaemia.3 The long term survival in BWS is favourable1, although surveillance for tumours is required.4 The phenotype of BWS is likely to result from an imbalance of a number of critical genes at chromosome 11p15. At this location, genetic imprinting with the loss of maternally expressed tumour and/or growth suppressor genes—for example, p57KIP2and H19—or duplications and unipaternal disomy of paternally expressed growth promoter genes—for example, insulin-like growth factor II—have been implicated in BWS.2 In BWS, 85% of cases are sporadic and 15% are autosomal dominant.2 Identified causes of autosomal dominant BWS include p57KIP2 mutations and 11p15 duplications and translocations.2 About 30% of the sporadic cases result from p57KIP2 mutations, unipaternal disomy, or 11p15 duplications and translocations, while 70% have no identified cytogenetic or DNA abnormality.2 View this table: Table 1 Features of Beckwith-Wiedemann syndrome The incidence of hypoglycaemia in BWS is about 50%.3 5 In one BWS hypoglycaemia series, 80% were reported as mild and asymptomatic, requiring extra feeds or intravenous dextrose only. In 20%, the hypoglycaemia was prolonged (duration greater than one week) and difficult to control.3Hypoglycaemia has been documented into the third year of life.5 Intellectual impairment was associated with hypoglycaemia.3 Hyperinsulinism and BWS Hyperinsulinism is the cause of both transient and prolonged hypoglycaemia in BWS. A number of case reports provide data on the metabolic aspects of …

Objective: To describe the aetiology, clinical features and appropriate treatment for hepatic glycogenosis in poorly controlled type 1 diabetes.Methods: A review of three adolescents with poor diabetes control, hepatomegaly and elevated serum liver transaminase concentrations.Results: Symptoms included abdominal pain, anorexia, nausea and vomiting. All had tender hepatomegaly; two had splenomegaly. Liver biopsy was performed on two patients. Histology revealed hepatic glycogenosis in both; one also demonstrated macrovesicular steatosis. With improved glycaemic control, all three showed resolution of their symptoms, organomegaly and elevated serum liver transaminase concentrations.Conclusions: Insulin-reversible hepatic glycogenosis is the most common cause of hepatomegaly and raised serum liver transaminase concentrations in children and adolescents with type 1 diabetes. Having excluded other causes of hepatic dysfunction, a 4 week therapeutic trial of improved glycaemic control is recommended prior to more invasive investigations.

Dance has been found to both enhance and undermine body image. Most of the literature has focused on ballet dancers and has neglected the role of identity as a dancer. This study assessed general and dance specific body image and dancer identity in 77 female modern dancers. Compared to samples of non-clinical college women, this sample had higher body appreciation and lower drive for thinness and self-objectification. White dancers in the sample also had positive levels of dancer body efficacy/acceptance whereas as non-White dancers had negative levels of this variable. Identity as a dancer was negatively correlated with body appreciation and dancer body perceptions and not related to the number of years of dance experience. Of general and dance specific body image, body appreciation emerged as the unique predictor. The findings warrant further research on positive body image, modern dancers, and identity.