De novo c.2455C>T mutation of NPR2 gene in a fetus with shortened long bones and a ventricular septal defect conceived by a mother with a fragile site at 16q22.1 and a father with a rare heterochromatic variant of chromosome 4 from Vietnam.

BACKGROUND: A heterozygous natriuretic peptide receptor 2 (NPR2) gene c.2455C>T mutation was identified as a cause of familial idiopathic short stature (ISS). Only two cases with this mutation were reported previously, and the probands with ISS had no organ system defects. METHODS: Next-generation sequencing (NGS) was performed on an amniotic fluid DNA sample of a fetus with shortened long bones and a small ventricular septal defect detected by an obstetric ultrasound examination. The pathogenic variant of the fetus was confirmed by Sanger sequencing. Sanger sequencing, G-banded, and C-banded karyotyping of the fetus's parents were subsequently performed. RESULTS: A de novo NPR2 gene c.2455C>T, p.(Arg819Cys) mutation was identified in the fetus. No microdeletion or microduplication was identified in the fetus by copy number variation sequencing with a maximum resolution of 400 kb. The two previous miscarriages experienced by the fetus's parents were interpreted as a result of chromosomal aberrations, including a maternal fragile site at 16q22.1 and a rare paternal variant involving in a large G-band-positive and C-band-positive block of paracentric heterochromatin of chromosome 4p. CONCLUSION: This report provides clinical signs of a de novo heterozygous NPR2 gene c.2455C>T mutation in the fetus and shows paternal chromosomal aberrations causing repeated pregnancy loss.

Congenital limb deficiency requiring transfemoral amputation.

A healthy female infant was born from a twin pregnancy with an isolated congenital lower extremity malformation. Aside from prenatally diagnosed polyhydramnios, the infant had normal prenatal and postnatal diagnostic workup. She underwent transfemoral amputation and healed uneventfully. Congenital limb anomalies may be the result of an unidentified amniotic band, thromboembolic event or twin-twin transfusion syndrome, though in this case, prenatal screening did not indicate any evidence of a limb anomaly and postnatal workup was negative.

Common Patterns of Congenital Lower Extremity Shortening: Diagnosis, Classification, and Follow-up.

Congenital lower limb shortening is a group of relatively rare, heterogeneous disorders. Proximal focal femoral deficiency (PFFD) and fibular hemimelia (FH) are the most common pathologic entities in this disease spectrum. PFFD is characterized by variable degrees of shortening or absence of the femoral head, with associated dysplasia of the acetabulum and femoral shaft. FH ranges from mild hypoplasia to complete absence of the fibula with variable shortening of the tibia. The development of the lower limb requires complex and precise gene interactions. Although the etiologies of PFFD and FH remain unknown, there is a strong association between the two disorders. Associated congenital defects in the lower extremity are found in more than 50% of patients with PFFD, ipsilateral FH being the most common. FH also has a strong association with shortening and bowing of the tibia and with foot deformities such as absence of the lateral rays of the foot. Early diagnosis and radiologic classification of these abnormalities are imperative for appropriate management and surgical planning. Plain radiography remains the main diagnostic imaging modality for both PFFD and FH, and appropriate description of the osseous abnormalities seen on radiographs allows accurate classification, prognostic evaluation, and surgical planning. Minor malformations may commonly be misdiagnosed.

Relationship between bent long bones, bent scapulae, and wavy ribs: malformations or variations?

BACKGROUND: Shortened and bent long bones and bent scapulae are sometimes reported in fetuses with wavy ribs (Carney and Kimmel, ). Wavy ribs are typically seen in the presence of maternal and developmental toxicity, are transient and reversible postnatally, and are considered to be variations rather than malformations. METHODS: We further assessed the literature cited in Kimmel and Carney () as well as papers published since then to determine under what conditions bent long bones in the absence of gross limb defects and bent scapulae were reported and whether information was available on the transient or permanent nature of these effects. RESULTS: Long bone and/or scapular changes almost always occurred at a lower incidence than wavy ribs. In every case, maternal and fetal toxicity occurred at the same dose levels. In a few studies, pups were followed sequentially after birth and bent long bones and scapulae were transient in nature and appeared normal by the time of weaning. Rabbits were much less likely to show wavy ribs or long bone and scapular changes at birth, even in the presence of severe maternal and fetal toxicity. This species difference may be due in part to the great increase in bone mass and remodeling that occurs during the first few postnatal weeks in rodents, but which takes place during the longer fetal period in rabbits. CONCLUSION: Our conclusion from this review is that bent long bones and scapulae, like wavy ribs, appear to be secondary to maternal and developmental toxicity, are transient, and like wavy ribs should be considered variations rather than malformations.

Comparative clinical study on deformity correction accuracy of different external fixators.

PURPOSE: In this study, the correction accuracy of Smart Correction spatial fixators and of Ilizarov-type external fixators are compared in terms of deformity complexity. METHODS: Seventy-seven (40 male, 37 female) bone segments of 57 patients treated with a Smart Correction device were compared with 94 (51 male, 43 female) segments of 68 patients treated with an Ilizarov fixator. Mean age of the Smart Correction group was 20.69 ± 12.94 years, and or the Ilizarov group 22.45 ± 12.18 years. Patients were categorised according to limb lengthening and the number of deformity planes. RESULTS: A longer correction period was found with Ilizarov (66.53 ± 47.7 days) compared with Smart Correction (49.05 ± 35.6 days) devices. The bone healing index of the Ilizarov group was significantly better compared with the spatial group. Residual deformity after treatment was significantly lower with the Smart Correction device; however, this relationship could not be shown between subgroups. Although there was no significant difference between subgroups, mean residual deformity was higher with the increasing number of planes of the deformity. CONCLUSIONS: The Smart Correction fixator is an accurate device that allows ease of application and planning. It demonstrates higher accuracy for correcting deformities compared with an Ilizarov external fixator. With an increasing number of planes, the difference between the two devices becomes even more pronounced. The relationship between the complexity of the deformity and residual deformity may possibly be significantly greater in favour of the Smart Correction fixator in a study with a larger sample size.

Absent sella turcica: a case report and a review of the literature.

Absent sella turcica is an extremely rare and dramatic radiographic finding. It may be isolated or occur in the presence of other anomalies, often involving the adenohypophysis. Our evaluation of a female infant with multiple anomalies including absence of the sella turcica, a normal pituitary in the craniopharyngeal canal, normal pituitary function, choanal atresia and anomalies of the appendiceal skeleton prompted a review of the occurrence and biology of an absent sella turcica.

Extra phenotypic features in a girl with Miller syndrome.

A 4-year-old girl, the child of nonconsanguineous parents was referred for clinical assessment because of postaxial limb defects associated with mild facial dysmorphism. The overall phenotypic features were compatible with the Miller syndrome. The proband manifested distinctive bone defects, consisting of triangular-shaped terminal phalanges and cone-shaped epiphyses of the middle phalanges of the feet. Using the sequence analysis of the DHODH gene we identified compound heterozygous mutations in the proband. Furthermore, both the parents were found to be heterozygous carriers of one of the two mutations found in the proband. Interestingly, the father had a history of postaxial polydactyly. We speculated that the postaxial polydactyly in the father was either a heterozygote manifestation or is unrelated.

Evolution of the radiographic appearance of the metaphyses over the first year of life in type V osteogenesis imperfecta: clues to pathogenesis.

We present the first report of the development of characteristic radiologic appearances of long bones during the first year of life in an infant with type V osteogenesis imperfecta (OI). We show the evolution of metaphyseal abnormalities from a rickets-like appearance to the classically described dense metaphyseal bands. These abnormalities suggest that the underlying defect in type V OI may involve a molecule common to both bone and cartilage that is involved in the regulation of growth plate development and metadiaphyseal ossification. Our findings provide new insights into skeletal development in type V OI and potentially yield useful clues to the identity of the defect underpinning the condition.

Camptomelia in a rhesus macaque (Macaca mulatta).

An 8.5-mo-old female rhesus macaque was examined for an apparent lump on the right arm, below the elbow. The macaque showed no signs of pain or discomfort. Examination revealed that the lump was actually a bend in the forearm. Radiography demonstrated that some of the long bones of the animal were bowed. Differential diagnoses included rickets, hyperparathyroidism, pseudohyperparathyroidism, and a growth dysplasia. No other similar abnormalities in animals from that cage or any other enclosure in our large colony were observed. Blood chemistries and a complete hemogram were within normal limits for a macaque of this age. Serum was submitted for a vitamin D profile that included assays for parathyroid hormone, 25-hydroxyvitamin D, and ionized calcium. Serum samples from sex- and age-matched normal controls were sent for comparison and to establish a baseline profile. The affected animal had vitamin D levels comparable to unaffected controls. Bone biopsies appeared normal for a macaque of this age. Fluorine levels in the drinking water supply were within acceptable limits. Consistent with the information available, a diagnosis of idiopathic camptomelia, or bowing of the long bones, was made. In humans, developmental camptomelia is associated with several bone dysplasias in infants and children. These conditions are thought to be caused by genetic mutations in enzymes or transcription factors that control development of the epiphyses and are almost always associated with other lethal and nonlethal developmental abnormalities.

[Total knee replacement in joints with severe varus and bone deficiency]. / Endoprotezoplastyka stawu kolanowego ze znaczna szpotawoscia i deficytem kostnym.

INTRODUCTION: Total knee replacement in knees with severe valgus and defects of the medial tibial condyle are at higher risk complications than in knees with a correct axial allignement. MATERIAL AND METHODS: The study group included 10 patients (11 knees) with with severe valgus and defects of the medial tibial condyle in which TKR was performed. In 8 cases bone defects were filled with bone autograft in 3 cases defects were filled with metal augments. The mean follow-up was 37 months (26 months to 4 years). Clinical results were measured with the knee society score, the level of activity was evaluated with the UCLA score. Radiographic evaluation was based on radiograms taken preoperatively, postoperatively and at the follow-up examination. RESULTS: In All cases an improvement in clinical results was noted, the mean KSS result rised from 25.3 preoperatively to 87 postoperatively and the level of activity rised from 3.4 to 5.4 postoperatively. No signs of loosening were found in radiographic evaluation. CONCLUSIONS: TKR in joint with severe varus and medial tibial condyle defects creates a need for the reconstruction of defects. In lesser defects reconstruction with bone autografts is sufficient, in severe cases filling the defect with metal augments is needed. When indicitions are followed both methods provide good clinical results.

Metaphyseal fragmentation with physiologic bowing: a finding not to be confused with the classic metaphyseal lesion.

OBJECTIVE: The purpose of this study was to describe the varied appearances of metaphyseal fragmentation associated with physiologic bowing and to estimate their frequency in children undergoing radiographic evaluation. CONCLUSION: The results of this study suggest that metaphyseal fragmentation is occasionally encountered in children with physiologic bowing. Results of a systematic imaging assessment should minimize confusion of this innocent radiologic alteration with the classic metaphyseal lesion of child abuse.

An MRI-based technique for assessment of lower extremity deformities-reproducibility, accuracy, and clinical application.

The hypothesis of this study was that length, torsion, and axis of a leg phantom can be measured accurately and reproducibly by magnetic resonance imaging (MRI) and that this can be applied to patients with leg deformities. Two phantoms and 30 patients (genu varum, n = 15; genu valgum, n = 15) were investigated using an optimized MRI technique. Reference measurements were performed with a micrometer screw and a goniometer. Patient leg length and axis were compared with long radiographs in bipedal stance. Intra- and interobserver reproducibility and accuracy were calculated using the mean absolute difference (MAD) and the 95% confidence interval. In patients, comparisons were done using a paired Student's t-test. MAD, intraobserver MAD, and interobserver MAD were 0.03, 0.03, 0.04 mm (length); 0.98, 1.2, 0.98 degrees (torsion); and 0.18, 0.23, 0.22 degrees (axis), respectively. In patients, leg length was underestimated by MRI (-2.4 +/- 0.7%; 1.9 +/- 0.7 cm; P < 0.001). The hip-knee-ankle angle (HKA) did not show significant differences in varus knees (-0.5 +/- 1.0 degrees ; P > 0.05), while it was significantly underestimated in valgus knees (-3.6 +/- 2.8 degrees ; P < 0.05). The phantom study revealed that leg length, torsion, and axis can be measured accurately and reproducibly by MRI. Although underestimation of leg length and HKA in valgus knees occurred, this optimized MRI technique can be applied to patients with leg deformities.

Skeletal asymmetry.

Bilateral variations in dimensions of upper and lower limb bones are attributable to difference in mechanical stress and strain that the bones are subjected to during bone growth, and is referred to as directional asymmetry. This skeletal asymmetry in the upper limbs is usually prominent on the dominant side while in lower limbs on the other side, possibly due to supportive contra lateral muscle contractions, that influence the bone growth. This contra lateral dominance in upper and lower limbs is known as cross-symmetry pattern. During skeletal remains examination, variations in different dimensions of long bones of an individual can result in erroneous opinion regarding number of individuals, especially in case of mass disasters. A case report of skeletal remains examination with review of relevant literature is presented where the different dimensions of right and left limb elements are measured and compared.

Terminal hemimelia of the lower extremity: absent lateral ray and a normal fibula.

Congenital lateral ray deficiency is considered to be a manifestation of fibular hemimelia. However, we have noted patients with absent lateral ray but stable knee and ankle joints, and named this condition terminal hemimelia of the lower extremity. This study was undertaken to further define this group of patients and to compare these patients with fibular hemimelia patients. Four boys and one girl of mean age six years two months were in the terminal hemimelic group and four boys and three girls of mean age eight years seven months in the fibular hemimelic group at the final evaluation. Clinical features commonly observed in the fibular hemimelia such as knee valgus, knee instability, tibial bowing, ball and socket ankle, ankle instability, tarsal coalition, leg length inequality were compared between both groups. Terminal hemimelia of the lower extremity was the same as fibular hemimelia in clinical features below the ankle joint. However, terminal hemimela was found to be milder than fibular hemimelia in terms of limb shortening. The clinical features above the ankle joint were different between both groups. Knees and ankles were stable, and gait disturbance were rarely noticed in patients with terminal hemimelia of the lower extremity.

Use of the Ilizarov method to correct lower limb deformities in children and adolescents.

The introduction to the West in the early 1980s of the Ilizarov circular external fixator and method resulted in rapid advances in limb lengthening, deformity correction, and segmental long-bone defect reconstruction. The mechanical features of and biologic response to using distraction osteogenesis with the circular external fixator are the unique aspects of Ilizarov's contribution. The most common indications for children and adolescents are limb lengthening and angular deformity correction. Surgical application and postoperative management of the device require diligent attention to detail by both patient and surgeon. Also required of the surgeon is a thorough appreciation of the basic principles of the apparatus, mechanical axial realignment, potential complications, and biologic response to stretching.