A child with split-hand/foot associated with tibial hemimelia (SHFLD syndrome) and thrombocytopenia maps to chromosome region 17p13.3.

We describe a-2-year-old boy who presented with a neonatal history of thrombocytopenia associated with a constellation of limb malformations mimicking split hand/foot malformation with long bone deficiency (SHFLD) syndrome. Limb malformations consisted of unilateral monodactyly with radial aplasia, unilateral split foot and bilateral club foot. Tibial aplasia of one limb and tibial hypoplasia of the other limb were notable. Partial agenesis of the sacrum was additional skeletal malformation. Craniofacial features included dense thick scalp hair, narrow frontal area, thick eye-brows, deep-set eyes, depressed nasal bridge, and small overhanging nasal tip, full-cheeks, and large ears. Array-CGH showed duplication of the short arm of chromosome 17p13.3 in the boy and his father, respectively. The father was free from any skeletal abnormalities, though he shares similar craniofacial dysmorphic features like his son. In addition, a paternal sib (uncle of the proband) manifested a phenotype similar to that of the proband. To the best of our knowledge the overall phenotypic and genotypic characterizations were consistent but not completely compatible with the traditional type of TAR syndrome or with SHFLD syndrome. We report on what might be a novel variant of SHFLD associated with transient thrombocytopenia, dysmorphic facial features, and a constellation of bone malformations.

[Clubfoot associated with tibial and fibular hemimelia]. / Der Klumpfuß bei tibialer und fibularer Hemimelie.

AIM: Clubfoot is rarely associated with tibial or fibular hemimelia. Treatment is complex and in most of the cases extensive surgery is required. At present experience with Ponseti casting is limited. We describe casting and surgical treatment of 10 clubfeet associated with tibial and fibular hemimelia. MATERIAL AND METHOD: Between 1.1.2004 and 31.12.2009 398 clubfeet were treated with casting in our institution. In the same period 10 clubfeet were associated with fibular or tibial hemimelia. Treatment started in 9 clubfeet with Ponseti manipulation and casting. We used the classification of Weber for tibial hemimelia and the Kalamchi-Achterman classification and Paley classification for fibular hemimelia. Data of all patients were prospectively documented and the result of the foot deformity was evaluated before a first lengthening procedure. Documentation included patient data, associated foot pathologies, surgical procedures, functional results. Functional results were evaluated before the first lengthening procedure started. RESULTS: Three patients had tibial hemimelia, two Weber type 1, one Weber type 2, one Weber type 3. five patients had fibular hemimelia, Paley type IV or Kalamchi-Achterman Type IA. One child had bilateral fibular hemimelia. The prospective leg length discrepancy ranged from 3.2 cm to 14 cm. Four feet had initially a successful treatment with casting. In a type 2 according to Weber we performed an ankle reconstruction procedure to correct tibiofibular diastases. Four feet underwent PMR. We had four relapses. Two equinus relapses were treated with a posterior release. Two severe relapses were finally corrected with resection of the coalition and midfoot osteotomies. In a Weber type 3 case a complex reconstruction was performed using an Ilisarov and a TSF frame. Functional results showed in a mean follow-up of 42.2 months (24-72 months) a dorsiflexion between 5 and 20° (Ø 7.7°) and a plantarflexion between 10 and 40° (Ø 26.1°). CONCLUSION: Treatment of clubfoot associated with tibial or fibular hemimelia with the Ponseti technique is limited because of complex hindfoot deformities including tarsal coalitions. Nevertheless treatment after birth starts with casting. Only mild cases of hemimelia without coalition can be corrected with the Ponseti technique. In a case of tibiofibular diastasis successful casting is possible, but extensive surgery is often necessary. In more severe cases we do not recommend casting. In these cases surgical treatment, including posteromedial release, osteotomies for the hindfoot, resection of coalitions or complex osteotomies with Ilisarov or TSF frame is the treatment of choice.

Guided growth for pathological physes: radiographic improvement during realignment.

BACKGROUND: Children with rickets are prone to having deformities of the lower extremities that are bilateral and often symmetrical. Although initially attributed to pathological or "sick" physes, the deformities are eventually seen in the metaphyses and diaphyses of the long bones; if left untreated, they may result in bone pain and stress fractures. The orthopaedists' role in managing these children is to correct and maintain alignment. Alternatively, we have exploited the use of hemiepiphysiodesis or guided growth, using staples or, more recently, the 8-plate (Orthofix, Verona, Italy). While gradually normalizing the mechanical axis, we have noted improvement in the appearance and width of all of the ipsilateral physes, not only at the knee but at the hip and ankle as well. This report summarizes our observations of the effects on the pathological physes in a group of patients with rickets who were preferentially treated with guided growth, often starting at a young age. METHOD: This retrospective review approved by an institutional review board included 14 children with rickets, including 10 treated with staples and 4 with 8-plates, who collectively underwent a total of 68 hemiepiphysiodeses (guided growth) and 35 osteotomies. Each was under appropriate medical management during the entire course of treatment, before and after surgery. We measured the mechanical axis deviation and anatomic angles of the femur and proximal tibia, noting the width and appearance of their physes at the hips, knees, and ankles preoperatively and upon correction of the axis. RESULTS: Of the 10 stapled patients, we noted 24 (45%) of 53 migrations and 41% rebound deformity. Four patients with 15 deformities that corrected with 8-plates experienced no hardware migration; for them, it is too early to comment on rebound deformity. While gradually correcting the mechanical axis, we have noted improvement in the appearance and width, not only of the pan-genu physes but also of remote physes at the hip and ankle. We suspect that the improved quality of the physes reflects not only the normalization of the mechanical axis but also the corresponding resolution of the waddling (varus) or circumduction (valgus) gait pattern. CONCLUSION: We recommend early intervention, via guided growth, to restore and preserve a neutral axis so that the child can enjoy a normal lifestyle while maximizing the growth potential of his or her physes, not only of the knees but the hips and ankles as well. We believe that by correcting and maintaining alignment, secondary bony deformities may be ameliorated and osteotomies for angular correction deferred if not avoided altogether. LEVEL OF EVIDENCE: IV (retrospective clinical series).

Disrupted bone metabolism in contaminant-exposed white storks (Ciconia ciconia) in southwestern Spain.

In 1998, the Aznalcóllar mine tailings dyke in southwestern Spain broke, flooding the Agrio-Guadiamar river system with acid tailings up to the borders of one of the largest breeding colonies of white storks in the western Palearctic, Dehesa de Abajo. Over the following years, a high proportion of nestlings developed leg defects not seen before the spill, prompting this study. Nestlings with deformed legs had significantly lower plasma phosphorous (P) and higher Ca:P ratios than non-deformed cohorts in the first two years, but in the third year, when more, younger birds were studied, plasma P ranged from much higher to much lower in the affected colony compared with reference birds. Coefficients of variation for phosphorous were 19% and 60%, in reference and contaminated colonies, respectively. Storks from the contaminated colony were unable to control P levels and Ca:P ratios within the narrow limits necessary for normal bone development.

Radiographic characteristics of lower-extremity bowing in children.

Lower-extremity bowing is common in infants and children and can result from a variety of conditions. At radiography, developmental bowing shows varus angulation centered at the knee, "metaphyseal beaking," thickening of the medial tibial cortices, and tilted ankle joints. Tibia vara (Blount disease) demonstrates genu varum and depression of the proximal tibia medially. Congenital bowing manifests as posteromedial bowing with cortical thickening along the concavity of the curvature and, in some cases, diaphyseal broadening. In rickets, radiographic changes occur primarily at sites of rapid growth and are predominantly metaphyseal, with widening of the zone of provisional calcification. Achondroplasia is characterized by shortening and thickening of the long bones with metaphyseal flaring and cupping. In neurofibromatosis, there may be anterolateral bowing of the tibia, and there is often focal narrowing and intramedullary sclerosis or cystic change at the apex of the angulation. The tibia is typically involved at the junction of the middle and distal thirds. Osteogenesis imperfecta demonstrates bowing from softening due to osteoporosis and multiple fractures and typically involves the entire skeleton. In camptomelic dysplasia, lower-extremity bowing is associated with a short trunk, short limbs, and deficiencies in pelvic bone development. Recognition of these pathologic conditions is important for differentiating those that will resolve spontaneously from those that require surgery or other treatment.

Reversible skeletal abnormalities in gamma-glutamyl transpeptidase-deficient mice.

Gamma-glutamyl transpeptidase (GGT) is a widely distributed ectopeptidase responsible for the degradation of glutathione in the gamma-glutamyl cycle. This cycle is implicated in the metabolism of cysteine, and absence of GGT causes a severe intracellular decrease in this amino acid. GGT-deficient (GGT-/-) mice have multiple metabolic abnormalities and are dwarf. We show here that this latter phenotype is due to a decreased of the growth plate cartilage total height resulting from a proliferative defect of chondrocytes. In addition, analysis of vertebrae and tibiae of GGT-/- mice revealed a severe osteopenia. Histomorphometric studies showed that this low bone mass phenotype results from an increased osteoclast number and activity as well as from a marked decrease in osteoblast activity. Interestingly, neither osteoblasts, osteoclasts, nor chondrocytes express GGT, suggesting that the observed defects are secondary to other abnormalities. N-acetylcysteine supplementation has been shown to reverse the metabolic abnormalities of the GGT-/- mice and in particular to restore the level of IGF-1 and sex steroids in these mice. Consistent with these previous observations, N-acetylcysteine treatment of GGT-/- mice ameliorates their skeletal abnormalities by normalizing chondrocytes proliferation and osteoblastic function. In contrast, resorbtion parameters are only partially normalized in GGT-/- N-acetylcysteine-treated mice, suggesting that GGT regulates osteoclast biology at least partly independently of these hormones. These results establish the importance of cysteine metabolism for the regulation of bone remodeling and longitudinal growth.

Aluminum effects on blood chemistry and long bone development in the chick embryo.

Body growth, blood chemistry, and long bone development of 10- to 16-day chick embryos (Gallus gallus) treated with aluminum (Al) citrate, sodium (Na) citrate, or sodium chloride (NaCl) were investigated. Two administration protocols were used. Acutely-treated embryos received 6.0 mumol Al citrate or Na citrate on day 8 of incubation. Chronically-treated embryos received a daily dose of 1.5 mumol Al citrate or Na citrate beginning on day 8 of incubation. For both protocols, Al citrate and Na citrate had no significant influence on viability or body weight. Al citrate-treated embryos had: (a) significantly shorter mean tibia lengths by day 16 of incubation, (b) a consistently lower ratio of tibia length: body weight on all days investigated, and (c) a persistent mid-diaphyseal malformation (angulation) of the femur and tibia. Spatially correlated with the malformation was a calcification defect detected by alizarin red S staining of intact tibias and the accumulation of aluminum as demonstrated by acid solochrome azurine staining of histological sections. Aluminum was localized at the mineralization front of the osteogenic collar surrounding the cartilage core of the tibia. Aluminum citrate or Na citrate had no significant effect on serum total calcium, inorganic phosphorus, total alkaline phosphatase activity, or creatinine, except for a transitory hypercalcemia (day 10) and phosphatemia (days 10 and 12) in Al citrate-treated embryos. The concomitant localization of Al and the early calcification defect in the region of tibial malformation implicate aluminum in the pathogenesis of the skeletal abnormality.

Broiler chicks fed low calcium diets. 1. Influence of zeolite on growth rate and parameters of bone metabolism.

An experiment with a factorial arrangement of treatments was conducted using five levels of dietary calcium and two levels of zeolite A. When dietary calcium was deficient or marginal, zeolite A improved calcium utilization, as evidenced by improved growth rate and a reduction in rachitic lesions. There was little benefit from adding zeolite A to diets adequate in calcium. The effect of zeolite A on the incidence of tibial dyschondroplasia was inconsistent.

Effect of calcium and phosphorus on the incidence of leg abnormalities in growing broilers.

Experiments were conducted to determine the effect of various dietary levels of Ca and P on growth and leg abnormalities in broiler cockerels fed corn and soybean meal diets varying in Ca and P content. Experiment 1 was a 2 x 4 factorial arrangement utilizing .77 and .97% Ca and .33, .38, .43, and .48% available (non-phytate) P (AP). The higher level of Ca reduced the growth rate of chicks fed low levels of AP. Neither Ca nor AP affected the incidence of crooked legs or dyschondroplasia. Increasing AP to .43% increased (P less than .05) the percentage of bone ash and bone weight. In Experiment 2, chicks were reared for 3 wk on diets containing either .40 or .50% AP. From 3 to 6 wk of age, the chicks were fed diets containing from .25 to .50% AP. The Ca:AP ratios were 2:1 in all diets. The level of AP in diets fed to 3 wk of age had no influence on chick growth, the incidence of crooked legs, or dyschondroplasia in either the starting or growing period. In Experiment 3, the chicks were reared in environmental chambers and from 3 to 6 wk of age and exposed to either constant temperature (27 C) and relative humidity (RH) (50%) or cyclic temperature (27 to 38 C) and RH (80 to 50%). The chicks were fed diets containing either .30% AP and .60% CA or .45% AP and .90% Ca from 3 to 6 wk of age. Cyclic temperature and higher RH depressed growth (P less than .05) but had no effect on the incidence of weak legs or dyschondroplasia.

Treatment of congenital and infantile pseudarthrosis of the tibia with pulsing electromagnetic fields.

The management of congenital and infantile pseudarthrosis of the tibia poses difficult problems because of the variability in the type and prognosis of the lesion and varied response to surgical treatment. Whatever the severity of the lesion, the use of pulsed electromagnetic fields can be expected to improve the prognosis for union by a factor of at least 20 per cent. In a very few patients, usually those with pseudarthrosis presenting later in life, pulsed electromagnetic fields alone together with plaster immobilization may be sufficient to produce union. In some, partially successful previous surgery may be made completely successful by subsequent application of pulsed electromagnetic fields. In patients with a fair or good prognosis as regards the type of lesion, a combination of surgery and pulsed electromagnetic treatment, some period of which may also be given before surgical treatment, gives a moderately high rate of success. In the three groups already described, the overall success rate is likely to be more than 70 per cent. In lesions with a poor prognosis, or after multiple surgical procedures in an older child, a combination of very adequate further surgery and pulsed electromagnetic fields can produce union in perhaps 30 per cent of cases, but it is unwise to commence any treatment if the limb is already unacceptably short, if there is gross wasting of the limb with evidence of inadequate vascular supply, and/or if the joints of the foot and ankle are stiff and associated with deformity. In such cases, the procedure of choice is amputation.

Biochemical and morphological changes associated with long bone abnormalities in silicon deficiency.

The purpose of this paper was to investigate long bone changes in silicon deficiency more extensively and under a new set of conditions. Long bone abnormalities have been produced in silicon-deficient chicks fed a casein-based rather than amino acid-based diet and under an entirely new set of conditions. As demonstrated previously feeding amino acid diets, the long bones of cockerels fed a silicon-supplemented basal diet and sacrificed at 4 weeks had a significantly greater amount of articular cartilage and water content as compared with the silicon-deficient group. Biochemical analyses of tibia for bone mineral, non-collagenous protein, hexosamine and collagen demonstrated that tibia from supplemented chicks had a significantly greater percentage and total amount of hexosamine and greater percentage of collagen than deficient chicks, the difference being greater for hexosamines than collagen. Tibia from silicon-deficient chicks also showed marked lesions, profound changes being demonstrated in epiphyseal cartilage, especially striking in the proliferative zone. The disturbed epiphyseal cartilage sequences resulted in defective endochondral bone growth indicating that silicon is involved in the metabolic chain of events required for the normal growth of bone.