Current state of the art in treatment of Mendelian disease: Skeletal dysplasias.

The current state of the art in treatment of Mendelian disease, specifically skeletal dysplasias, benefits tremendously from Dr. Victor McKusick's early delineation and standardization of the nomenclature surrounding these conditions. Through close observation and careful description of each dysplasia to flesh out the nosologic backbone of the genetic skeletal disorders, individuals with the same diagnosis were identified and grouped together for genetic interrogation. These efforts have resulted in the identification of the genetic etiology of nearly all recognized skeletal disorders. This, in turn, is leading to disease-specific treatment for many of the skeletal dysplasias in this new era of precision medicine. Furthermore, Dr. McKusick's natural history descriptions of many genetic skeletal disorders helped to establish the baseline disease state against which the effect of new treatment is compared.

Osteofibrous Dysplasia of the Tibia in Children: Outcome Without Resection.

BACKGROUND: The proposed association between osteofibrous dysplasia and adamantinoma has led some to advocate resection of the entire lesion, which can require major subsequent reconstruction. However, this link remains unproven and there is some support in more recent literature for a less aggressive approach. This study aims to describe our experience managing pediatric tibial osteofibrous dysplasia with such an approach and to report functional outcomes in children treated thus. METHODS: A total of 28 cases of osteofibrous dysplasia in 25 patients were managed at a referral center for pediatric bone tumors with observation in the first instance, then limited surgical intervention if required to address pain and deformity. Surgery aimed to restore stability and alignment without excising the lesion. Clinical records provided basic clinical outcome measures involving walking, recreation, orthoses and school/work participation and patients provided a Musculoskeletal Tumour Society score (MSTS) where contactable. RESULTS: Mean age at presentation was 6.0 years and mean follow-up was 8.3 years. Only 8 patients required surgery. According to basic outcome measures, 13 patients were symptom-free. About 15 patients (17 cases) provided a MSTS and the mean score was 24 of 30. No transformation to adamantinoma was observed. Those who presented at a younger age and with bilateral disease more often required surgery and remained symptomatic. CONCLUSIONS: A less aggressive approach to pediatric tibial osteofibrous dysplasia achieves good functional outcomes and patient satisfaction in most cases. Surgery is required in the minority of cases. Transformation to adamantinoma was not observed in this series. We recommend patient education, clinical observation and reactive intervention if required, rather than proactive resection and reconstruction. LEVEL OF EVIDENCE: Level IV-case series.

Management of symptomatic os acromiale: a survey of the American shoulder and elbow surgeons.

BACKGROUND: The purpose of this paper was to survey members of the American Shoulder and Elbow Surgeons (ASES) to assess their opinion on management options, help highlight important clinical factors, and elucidate surgical preferences for the treatment of a symptomatic meso-os. METHODS: An online questionnaire was distributed to the active members of the ASES. The survey queried surgeon demographics and perioperative management preferences, and presented multiple clinical case scenarios of patients with a presumed symptomatic, unstable os acromiale. RESULTS: There were 116 ASES members who responded to the survey, and 26% (n = 30) who stated they do not operatively manage a symptomatic os. We identified two main clusters of respondents. Cluster 1 (n = 67) (as compared to cluster 2, n = 19) was comprised of surgeons with significantly more experience treating a symptomatic os acromiale (p < 0.05). These surgeons regarded gender, age, BMI, and hand dominance as important clinical factors when deciding when to proceed to surgery. Overall, arthroscopic management of the os was preferred, but those surgeons more experienced in treating os acromiale preferred open reduction and internal fixation (ORIF) in specific clinical cases. CONCLUSION: The survey findings reflect the current lack of consensus in the treatment of a unstable, symptomatic os acromiale. Overall, arthroscopic management was preferred by most surgeons, though ORIF was preferred in certain clinical scenarios by those more experienced with os acromiale. The overall preference for arthroscopy suggests a possible shift in the treatment paradigm for patients with symptomatic meso-acromions, but higher level studies are needed to substantiate these findings.

Update on treatment of adolescent Blount disease.

PURPOSE OF REVIEW: Treatments available to correct adolescent Blount disease deformities differ in terms of features, advantages, and disadvantages. Each is indicated, therefore, for different scenarios of severity, physeal condition, and maturity. The purpose of this review is to update basic concepts, surgical treatments, and controversies concerning this disorder. RECENT FINDINGS: The cause of Blount disease is unknown although etiologic factors as morbid obesity and hypovitaminosis D are thought to be associated with it. Recently, semiinvasive techniques (guided growth) have been proposed for mild deformities but remain controversial. Osteotomies with external fixation (hexapodes) are still the most recommended corrective treatment in this condition. SUMMARY: Little is known about the origin and natural history of Blount disease. Treatment is always surgical and, given their complexity, should be preceded by a thorough analysis and planning regarding all deformities. Treatment principles are to correct the three-dimensional deformity and avoid recurrence. The choice of technique mainly depends on patient maturity and severity. Guided growth is a good choice for more immature patients with moderate deformities. Progressive correction using osteotomy or physeal distraction is indicated for patients with severe deformities and low remaining growth. The Taylor spatial frame is currently the most popular progressive correction device.

Optimal Treatment of Osteofibrous Dysplasia of the Tibia.

BACKGROUND: Our study of a large patient group reports on the behavior and postoperative recurrence of osteofibrous dysplasia (OFD). METHODS: We reviewed the medical records of 55 patients who were diagnosed with OFD of the tibia and showed typical features of this tumor. The patients' presentation, disease course, history of pathologic fracture, typical radiographic features, surgical treatment history, and surgical results were investigated. RESULTS: The longitudinal OFD lesion size peaks at a mean 13.3 years of age with a mean maximum proportionate size of 0.33. These lesions in 92% of the patients spontaneously presented with a stable disease course, while those in the other 8% continued increasing. There were no significant predictive factors of disease course. Among surgically treated lesions, we noted a higher rate of recurrence after curettage than after excision (P<0.001). Patients who underwent curettage and developed recurrence were significantly younger than those who did not (P=0.01). CONCLUSIONS: Our data suggest that observation can be the primary form of treatment for patients with OFD and that the disease would stop advancing with time. During observation, clinicians should carefully observe all patients with OFD because the relation between OFD and adamantinoma is unclear. If surgery is necessary due to severe morbidity, we recommend excision rather than curettage to prevent recurrence, especially for younger patients. LEVEL OF EVIDENCE: Level III.

Pediatric Orthopaedic Consults From Chiropractic Care.

Alternative medicine in pediatrics is expanding, with chiropractic now a common choice for families seeking alternative medical care. Currently, there is sparse information in the literature exploring the role of chiropractic in orthopaedic pathology. The objective of this case series is to present pediatric patients who received treatment from chiropractors and orthopaedic physicians as well as to review the respective existing research. Data collected included chiropractic diagnosis, orthopaedic diagnosis, imaging studies, treatments, and complications. Twenty-three patients were studied. Scoliosis, Legg-Calvé-Perthes disease, developmental dysplasia of the hip, cerebral palsy, skeletal dysplasia, and slipped capital femoral epiphysis were diagnoses included. Children had multiple sessions of chiropractic for management of these conditions. The parents' perception for chiropractic was positive in every case. Delayed referral, misdiagnosis, adverse events from manipulative therapy, and ineffective treatments were observed in the present study. More research is indicated to validate chiropractic in children with orthopaedic pathology. (Journal of Surgical Orthopaedic Advances 27(1):58-63, 2018).

Aplasia cutis congénita con defecto óseo subyacente: evolución favorable tras manejo conservador.

La aplasia cutis congénita es una rara alteración caracterizada por la ausencia de áreas localizadas de piel en el momento del nacimiento. Suele manifestarse como una lesión solitaria localizada principalmente en el cuero cabelludo, que puede estar asociada con otras malformaciones congénitas. Las complicaciones pueden ser fatales, por lo que es necesario un tratamiento individualizado que vendrá determinado por el tamaño, localización y grado de afectación de estructuras subyacentes. Presentamos un caso de aplasia cutis congénita del cuero cabelludo con múltiples lesiones y defecto óseo subyacente de 3 × 1.5 cm de tamaño, pero sin otras anomalías asociadas. El manejo conservador permitió una adecuada y completa epitelización cutánea con cierre del defecto óseo subyacente sin necesidad de procedimientos invasivos.

Adolescents and Young Adults with Chronic or End-Stage Kidney Disease.

BACKGROUND: Adolescents and young adults face unique and complex physical, psychological, and family challenges. Despite improvements in care for chronic kidney disease (CKD) and end-stage kidney disease (ESKD), long-term mortality for children, adolescents, and young adults with CKD remains substantially higher than their healthy counterparts. SUMMARY: In this article, we discuss the complex challenges that adolescent and young adult CKD/ESKD patients face. Adolescents have different CKD etiologies and progress along a course dissimilar to the adult population, but have similar multifarious comorbidities. In the setting of puberty and learning to become self-sufficient, adolescence is a critical time for growth and psychosocial development. Physiological complications of CKD underlie many of the long-term outcomes. CKD-mineral and bone disorder and anemia are particularly challenging given that they are exacerbated by the rapid growth of adolescents. Endocrine imbalances and malnutrition can delay and limit growth. All of these factors, together with family dynamics and socioeconomic status, contribute to the poor long-term outcomes and decreased quality of life (QoL) for these patients and their families. KEY MESSAGES: Care for the adolescent CKD/ESKD population is uniquely challenging, but research has identified ways in which we can continue to improve long-term outcomes and QoL for adolescents with CKD/ESKD.

The management of the painful bipartite patella: a systematic review.

PURPOSE: This study aimed to identify the most effective method for the treatment of the symptomatic bipartite patella. METHODS: A systematic review of the literature was completed, and all studies assessing the management of a bipartite patella were included. Owing to the paucity of randomised controlled trials, a narrative review of 22 studies was completed. A range of treatments were assessed: conservative measures, open and arthroscopic fixation or excision and soft tissue release and excision. RESULTS: All of the methods provided results ranging from good to excellent, with acceptable complication rates. CONCLUSIONS: This is a poorly answered treatment question. No firm guidance can be given as to the most appropriate method of treating the symptomatic bipartite patella. This study suggests that there are a number of effective treatments with acceptable complication rates and it may be that treatments that conserve the patella are more appropriate for larger fragments. LEVEL OF EVIDENCE: IV.

Total Knee Arthroplasty in Patients with Blount Disease or Blount-Like Deformity.

Blount disease is associated with complex deformity of the proximal tibia, and some patients will develop knee osteoarthritis. Five patients (eight knees) with Blount disease or Blount-like deformity underwent total knee arthroplasty. Mean proximal tibial metaphyseal-diaphyseal angle was 20.75°. Each patient had substantial posteromedial tibial bony defects and six knees required extensive medial releases. Two knees required increased constraint at index procedure. One patient has undergone bilateral revision surgery with rotating hinge prostheses. Mean WOMAC scores were 13.5 and Knee Society scores were 212.5 at average 75.2 month follow-up. Despite technical challenges, patients with these deformities can have successful outcomes after total knee arthroplasty. Surgeons should be prepared to address posteromedial tibial bony defects and consider constrained arthroplasty at the index procedure.

Evaluation of Short and Tall Stature in Children.

Short stature is defined as a height more than two standard deviations below the mean for age (less than the 3rd percentile). Tall stature is defined as a height more than two standard deviations above the mean for age (greater than the 97th percentile). The initial evaluation of short and tall stature should include a history and physical examination, accurate serial measurements, and determination of growth velocity, midparental height, and bone age. Common normal variants of short stature are familial short stature, constitutional delay of growth and puberty, and idiopathic short stature. Pathologic causes of short stature include chronic diseases; growth hormone deficiency; and genetic disorders, such as Turner syndrome. Tall stature has the same prevalence as short stature, but it is a much less common reason for referral to subspecialty care. Common causes of tall stature include familial tall stature, obesity, Klinefelter syndrome, Marfan syndrome, and precocious puberty. Although most children with short or tall stature have variants of normal growth, children who are more than three standard deviations from the mean for age are more likely to have underlying pathology. Evaluation for pathologic etiologies is guided by history and physical examination findings.

Treatment of Adolescent Blount Disease Using Taylor Spatial Frame With and Without Fibular Osteotomy: Is There any Difference?

BACKGROUND: In adolescents, Tibia Vara (Blount disease) patients usually present with combination of marked genu varum, procurvatum, and internal tibial torsion. When no growth remaining, standard treatment protocol for correction is osteotomy of the proximal tibia and fibula. In our study we compared 2 groups of patients: group A was treated with fibular osteotomy and group B was treated without fibular osteotomy. METHODS: Twenty-three patients (25 tibias), 21 males and 2 females, mean age of 14.7 years (range, 13 to 21 y) were included in our study. All patients underwent correction with Taylor spatial frame. Group A (with fibular osteotomy) included 11 tibias and group B (no fibular osteotomy) included 14 tibias. Group A underwent correction by proximal tibial and fibular osteotomies (fibula was fixed distally by 2 ilizarov wires to the distal ring). Group B was treated by proximal tibial osteotomy only (fibula was not osteotomized and was not fixed to the tibia). RESULTS: Correction goal was achieved in 9 cases in group A and 12 in group B. Mean time in frame was 15.9 weeks in group A and 14.14 in group B. Mean lengthening was 16.5 mm in group A and 12.8 mm in group B. Mean proximal tibia-fibula distance was 21.1 mm (group A) and 14.9 mm (group B). Mean distal tibia-fibula distance was 9.8 mm (group A) and 9.6 mm (group B). There was no ankle malalignment in both the groups. Complications included pin-tract infection in 11 patients and delayed union in 2 patients (1 in each group). CONCLUSION: We believe that in patients with minimal lengthening as needed in patients with adolescent Tibia Vara correction might be performed safely without osteotomy and fixation of the fibula. LEVEL OF EVIDENCE: Level III.

Eight years experience from a skeletal dysplasia referral center in a tertiary hospital in Southern India: a model for the diagnosis and treatment of rare diseases in a developing country.

We report on a series of 514 consecutive diagnoses of skeletal dysplasia made over an 8-year period at a tertiary hospital in Kerala, India. The most common diagnostic groups were dysostosis multiplex group (n = 73) followed by FGFR3 (n = 49) and osteogenesis imperfecta and decreased bone density group (n = 41). Molecular confirmation was obtained in 109 cases. Clinical and radiographic evaluation was obtained in close diagnostic collaboration with expert groups abroad through Internet communication for difficult cases. This has allowed for targeted biochemical and molecular studies leading to the correct identification of rare or novel conditions, which has not only helped affected families by allowing for improved genetic counseling and prenatal diagnosis but also resulted in several scientific contributions. We conclude that (1) the spectrum of genetic bone disease in Kerala, India, is similar to that of other parts of the world, but recessive entities may be more frequent because of widespread consanguinity; (2) prenatal detection of skeletal dysplasias remains relatively rare because of limited access to expert prenatal ultrasound facilities; (3) because of the low accessibility to molecular tests, precise clinical-radiographic phenotyping remains the mainstay of diagnosis and counseling and of gatekeeping to efficient laboratory testing; (4) good phenotyping allows, a significant contribution to the recognition and characterization of novel entities. We suggest that the tight collaboration between a local reference center with dedicated personnel and expert diagnostic networks may be a proficient model to bring current diagnostics to developing countries.

Multicenter study of Blount disease in Japan by the Japanese Pediatric Orthopaedic Association.

BACKGROUND: In order to investigate the epidemiology and features of Blount disease in Japan, the Japanese Pediatric Orthopaedic Association conducted a multicenter study on Blount disease in 2003. METHODS: Questionnaires were sent to 1,350 training hospitals of the Japanese Orthopaedic Association. This study included those with stage I or II diagnosed between 1990 and 2002 and those with stage III or higher diagnosed between 1980 and 2002 based on the Langenskiöld classification. The questionnaire items included age at diagnosis, sex, presence or absence of a family history of bowlegs, past history of trauma, birthplace, age when starting to walk, height and weight at the initial presentation, laterality of the affected knee, disease types (infantile or adolescent), treatments, and plain radiographic findings. RESULTS: The results for 212 patients with 296 affected knees were obtained. The disease types were infantile in 190 patients with 270 affected knees and adolescent in 22 patients with 26 affected knees. There were more girls among cases with both types. Among the infantile-type cases, there were more patients with bilaterally affected knees; however, in the adolescent-type cases, there were more patients with unilaterally affected knees. Patients with either type tended to be obese at diagnosis. There was little difference in age at which patients with either type started to walk, compared with the mean age for the general population. Conservative treatment was applied to most infantile-type cases in stage I or II, whereas surgery was performed in all but one of those with stage III or IV of the disease. Most adolescent-type cases underwent surgery. CONCLUSIONS: This was the first multicenter study on Blount disease in Japan. Among 296 knees, the majority of these knees had stage I or II Blount disease. Very few cases had stage III or higher disease, and there were 35 knees with the infantile type and 19 with the adolescent type in the 23 years from 1980 through 2002.

Dysplasia epiphysealis hemimelica - diagnostics and treatment in pediatric patients.

BACKGROUND: Dysplasia epiphysealis hemimelica, also known as Trevor-Fairbanks disease, is a rare developmental disorder The objective of this article is to present own observations and experience in treating patients with dysplasia epiphysealis hemimelica. MATERIAL AND METHODS: Six children with dysplasia epiphysealis hemimelica were treated in years 1990-2007. The mean age of observation was 8.5 years (from 3 to 19 years). Analysis of medical and radiological documentation of patients was performed to collect data on symptoms, disease location, management and outcomes. RESULTS: The main symptoms reported by patients included limited range of motion of the affected joints with pain (66%) and deformed joint outline (34%). Four patients were subjected to surgical treatment while conservative treatment was applied in the other two. Lated complications were observed in two patients after surgical intervention (50%). In patients undergoing conservative treatment, one positive outcome and one negative outcome involving complete hip ankylosis, were observed. CONCLUSIONS: Correct diagnosis is very important as it may save the patient from unnecessary surgery and, if the surgery is necessary, it may help in performing it correctly. In patients presenting with joint pains, joint deformations, and tuberous lesions in joints possibility of dysplasia epiphysealis hemimelica should be taken into account. The treatment should start with conservative treatment, particularly physical therapy applied in the region of pain. If pain, joint deformation or limited range of motion of the affected joint persist, surgical treatment consisting of complete excision of the lesion should be taken into account.

Osteofibrous dysplasia: a narrative review.

Osteofibrous dysplasia (OFD) is a rare, benign, self-limited bone disorder with a relatively low incidence, accounting for approximately 0.2% of all primary bone tumors. It was frequently found intra-cortical of the mid-shaft of the tibia. OFD can also occur in other skeletal regions, including the fibula, ulna, radius, femur, humerus, ischium, rib, tarsus, metatarsals, vertebral, and capitate. OFD can present with asymptomatic, mass, pain, swelling, deformity, and even pathological fracture. OFD might be misdiagnosed as adamantinoma (AD) and because they are three subtypes origin from the same family of bone tumors and have similar imaging features. Moreover, pathology could provide evidence for an accurate diagnosis of OFD, but misdiagnosis may occur due to small sampling materials. To date, few studies have comprehensively introduced the epidemiology, clinical manifestations, pathogenesis, radiological features, pathology, and treatment for OFD. We herein discuss clinical signs, diagnosis methods, and treatment options of OFD to improve the understanding of OFD, which is helpful for accurate diagnosis and appropriate treatment.

Blount disease.

In 1937, Blount described progressive tibial varus deformity observed in otherwise healthy children and adolescents. Although he called the condition "osteochondrosis deformans tibiae," the disorder is most frequently referred to as Blount disease. Two distinct clinical and radiographic forms have been recognized: infantile and adolescent. A third form, which was called "juvenile" Blount disease by Thompson, is recognized by some authors and is intermediate in severity and age of onset. The etiology of Blount disease is unknown. If the condition remains unresolved, it can lead to progressive varus deformity, with or without associated deformities of the distal femur and/or tibia; leg length inequality; and significant articular distortion, leading to premature osteoarthritis of the knee. A strong, but not universal, association exists between Blount disease and childhood obesity, increasing the prevalence and making effective treatment of this condition a challenge. Infantile Blount disease may resolve, respond to nonsurgical treatment, or be relentlessly progressive, so the surgeon must be astute in recognizing the features of true infantile Blount disease to determine effective treatment options.

[Fetal therapy of skeletal dysplasias].

Three types of fetal therapy of skeletal dysplasias, as enzyme replacement, in utero stem cell transplantation, and gene therapy, are reviewed. Clinical trial of recombinant ALP for infantile hypophosphatasia has already started in Japan. In future, such enzyme replacement therapy is expected to be adapted to fetus. There are several reports of mesenchymal stem cell transplantation for osteogenesis imperfecta fetus. These case reports have showed that stem cell transplantation is safe and to some extent works in patients. No clinical trial for gene therapy has been reported. Recently, the study of gene therapy of using HPP fetal mouse showed an excellent therapeutic effect. Fetal therapy of skeletal dysplasias is still the stage of research because of the safety and the ethical issues. However, in order to treat severe cases of skeletal dysplasias which abnormal development has been already completed at birth, fetal therapy at an early stage would be demanded.

Life span care for patients with skeletal dysplasia: A roadmap.

Patients with skeletal dysplasias usually experience health related problems in different parts and systems of the body. Therefore, they face challenges in multiple domains of functioning and health. To address these different domains, interdisciplinary care should be the standard for these patients. The basic algorithm of interdisciplinary care can be similar for patients with different skeletal dysplasias, as many of the problems and needs are generic within different age groups. With increased age the domains in which patients with skeletal dysplasia face challenges will change and the focus and frequency of the interdisciplinary care should change accordingly. Thorough understanding of the specific characteristics of different skeletal dysplasias is required to create an individualized efficient interdisciplinary screening and care program. This paper presents the current structure and rationale of the interdisciplinary screening and care program of the skeletal dysplasia expert center of the University Medical Center Utrecht in the Netherlands. It is presented here, tailored to osteogenesis imperfecta, but the structure of the program is generic for all skeletal dysplasias.

Elevated alpha-fetoprotein levels in Van Wyk-Grumbach syndrome: a case report and review of literature.

The association between primary hypothyroidism and precocious puberty secondary to ovarian hyperstimulation has been recognized for over a century. Here, we report the case of a 9-year-old girl with severe primary hypothyroidism, who presented with premature menarche, enlarged pituitary gland, enlarged ovaries with multiple cysts, and elevated prolactin and alpha-feto protein levels. Pituitary and ovarian radiology findings, and alpha-feto protein levels normalized a few weeks after hypothyroidism treatment was started. Reviewing the literature we found several reports of increased levels of tumor markers in girls with this association. Thyroid function tests should be always part of the evaluation of patients with precocious puberty especially if the bone age is delayed. Tumor markers and liver function tests may be abnormal in patients with severe hypothyroidism and improve soon after thyroid hormone replacement is started.