Colleen Ditro

Anesthetic care and perioperative complications of children with Morquio syndrome.

Objectives:  Our objective was to make recommendations based on our experience and findings from this study regarding the anesthetic care of children with Morquio syndrome (MS). We emphasize information not readily available in the Anesthesiology literature.

Skeletal Dysplasias: Evaluation with Impulse Oscillometry and Thoracoabdominal Motion Analysis

Children with skeletal dysplasia (SD) often have pulmonary disease, which can be life threatening. In clinical practice, chest wall and formal respiratory function tests are difficult to perform owing to the small size and cooperation. The objective of this study was to demonstrate distinct thoracopulmonary function patterns in children with SD.

Flexion-extension cervical spine MRI in children with skeletal dysplasia: is it safe and effective?

Background: Skeletal dysplasias may be associated with cervical spinal instability or stenosis. Cervical spine flexion-extension plain radiographs in children with skeletal dysplasia are difficult to interpret. The purpose of this study was to review the indications, efficacy, and safety of performing flexion-extension magnetic resonance imaging (MRI) under sedation/anesthesia in these children. Methods: Retrospective, Institutional Review Board–approved review of 31 children with skeletal dysplasia who underwent 38 cervical spine flexion-extension MRI studies under sedation/anesthesia. Indications included abnormal neurological examination, suspected instability, stenosis, or inconclusive findings on flexion-extension radiographs. Studies were performed by the radiology technologist as directed by the radiologist with an anesthesiologist present. MRI was evaluated for odontoid hypoplasia, os odontoideum, cerebrospinal fluid effacement, cord compression, spinal cord changes, cervical canal narrowing in the neutral, flexion, and extension positions. Neurological examinations were recorded before and after MRI to assess safety. Results: The average age at MRI was 3 years, 2 months. In 6 patients whose plain radiographs showed C1-C2 or subaxial instability, flexion-extension MRI showed no cord compression. Nine patients with inconclusive plain radiographs had abnormal MRI findings. An os odontoideum not seen on plain radiographs was diagnosed in 3 patients on flexion-extension MRI. On the basis of the MRI findings, 14 patients underwent surgery, 9/14 had increased cord compression in flexion or extension compared with neutral, and observation was continued in 17 others. Patients who underwent surgery had significant cord compression on MRI. There were no significant changes in the neurological examinations after MRI. Conclusions: Cervical spine flexion-extension MRI under sedation/anesthesia in children with skeletal dysplasia is safe under adequate supervision and is necessary to guide accurate medical and surgical decision making. Flexion-extension MRI is useful for identifying dynamic changes in canal diameter resulting in cord compression not seen on plain radiographs, and it is also useful for identifying patients with suspected plain film instability who may not have stenosis or cord compression on MRI. Study Design: Level IV—retrospective case series.

C-type natriuretic peptide plasma levels are elevated in subjects with achondroplasia, hypochondroplasia, and thanatophoric dysplasia

CONTEXT C-type natriuretic peptide (CNP) is a crucial regulator of endochondral bone growth. In a previous report of a child with acromesomelic dysplasia, Maroteaux type (AMDM), caused by loss-of-function of the CNP receptor (natriuretic peptide receptor-B [NPR-B]), plasma levels of CNP were elevated. In vitro studies have shown that activation of the MAPK kinase (MEK)/ERK MAPK pathway causes functional inhibition of NPR-B. Achondroplasia, hypochondroplasia, and thanatophoric dysplasia are syndromes of short-limbed dwarfism caused by activating mutations of fibroblast growth factor receptor-3, which result in overactivation of the MEK/ERK MAPK pathway. OBJECTIVE The purpose of this study was to determine whether these syndromes exhibit evidence of CNP resistance as reflected by increases in plasma CNP and its amino-terminal propeptide (NTproCNP). DESIGN This was a prospective, observational study. SUBJECTS Participants were 63 children and 20 adults with achondroplasia, 6 children with hypochondroplasia, 2 children with thanatophoric dysplasia, and 4 children and 1 adult with AMDM. RESULTS Plasma levels of CNP and NTproCNP were higher in children with achondroplasia with CNP SD scores (SDSs) of 1.0 (0.3-1.4) (median [interquartile range]) and NTproCNP SDSs of 1.4 (0.4-1.8; P < .0005). NTproCNP levels correlated with height velocity. Levels were also elevated in adults with achondroplasia (CNP SDSs of 1.5 [0.7-2.1] and NTproCNP SDSs of 0.5 [0.1-1.0], P < .005). In children with hypochondroplasia, CNP SDSs were 1.3 (0.7-1.5) (P = .08) and NTproCNP SDSs were 1.9 (1.8-2.3) (P < .05). In children with AMDM, CNP SDSs were 1.6 (1.4-3.3) and NTproCNP SDSs were 4.2 (2.7-6.2) (P < .01). CONCLUSIONS In these skeletal dysplasias, elevated plasma levels of proCNP products suggest the presence of tissue resistance to CNP.

Growth-sparing spinal instrumentation in skeletal dysplasia.

Study Design. Retrospective case series. Objective. To report the outcomes of distraction-based, growth-sparing spinal instrumentation in patients with skeletal dysplasia. Summary of Background Data. Patients with skeletal dysplasia with spinal deformity often undergo early fusion, further compromising an already small chest. Nonfusion techniques may provide a safe alternative and allow for thoracic growth. Methods. Between 2004 and 2010, 12 children with a diagnosis of various types of skeletal dysplasia underwent growth-sparing spinal instrumentation for severe spinal deformities. The mean duration of treatment with growing rods was 57 months (42–84 mo). Nine patients were treated with growing rods (8 dual, 1 single), and 3 were treated with vertical expandable prosthetic titanium rib (VEPTR; Synthes). Preoperative, initial postoperative, and final follow-up anteroposterior and lateral spine radiographs were measured for magnitude of deformity, junctional kyphosis, and implant failure. Results. The major curve Cobb angle improved from a mean of 79° preoperatively to a mean of 41° at the last follow-up (52%). There was a decrease in mean thoracic kyphosis from 77° preoperatively to 64° at final follow-up and an increase in mean lumbar lordosis from 58° preoperatively to 63° at final follow-up. The mean space available for the lungs increased by 26 mm on the concave and 24 mm on the convex side. Six patients required revision surgery for proximal junctional kyphosis. There were 4 rod failures and 6 hook and 8 screw dislodgements. One patient with vertical expandable prosthetic titanium rib had failed rib fixation that required revision. Conclusion. Growth-sparing spinal instrumentation in patients with skeletal dysplasia and severe spinal deformity has a high complication and revision rate, and surgeons should closely monitor these patients. The complication rate is comparable with previous reports on patients with other diagnoses. However, deformities were well controlled, some trunk growth was achieved, and fusion surgery was delayed in all cases. Level of Evidence: 4

Occipitocervical fusion in skeletal dysplasia: a new surgical technique.

Study Design. Retrospective cohort study. Objective. This study describes clinical and radiological results of a new cable technique for occipitocervical fusion (OCF) in children with skeletal dysplasia (SD). Summary of Background Data. Anatomical variability and poor bone quality make upper cervical surgery technically challenging in patients with SD. We present a new cable technique for OCF in children with SD when the posterior elements are not of a size or quality for other types of instrumentation. Methods. Retrospective review of 24 patients with SD (8 boys, 16 girls) who underwent OCF between 2001 and 2011. In this technique, cables provide compression across a bone graft that is prevented from entering the canal and the graft resists excessive lordosis. Demographic and radiographical data are presented. All patients were followed for initial outcomes of surgery, and 20 patients (83%) were followed for 2 years or more for mid- and long-term outcomes. Results. Mean age at surgery was 6.5 years and mean follow-up was 4.1 ± 2.4 years. This technique was used as a primary procedure in 20 and a revision procedure in 4 patients. Diagnoses included Morquio syndrome (6), spondyloepiphyseal dysplasia (9), spondyloepimetaphyseal dysplasia (5), metatropic dysplasia (3), and Kniest syndrome (1). Ten patients had upper cervical instability and features of cervical myelopathy, and the remaining 14 patients had instability and signal changes on magnetic resonance image. Fusion extended from occiput to C2 in 71% patients, and upper cervical decompression was needed in 92% patients. Postoperatively, all patients were immobilized in a halo vest for mean duration of 12 weeks. Fusion was achieved in all patients. Complications included halo pin-tract infections (7), junctional instability (2), and extension of fusion (4). Conclusion. This new cable technique is a good alternative for OCF in patients with SD who have altered anatomy at the craniocervical junction not amenable to rigid internal fixation. Level of Evidence: 4

Gait Pattern and Lower Extremity Alignment in Children With Diastrophic Dysplasia.

Background: The aim of this study was to describe the dynamic lower extremity alignment in children with diastrophic dysplasia (DD) by 3-dimensional gait analyses. Our main hypothesis was that gait kinematics and kinetics are different than the age-normalized population and patellar dislocation can alter the gait in patients with DD. Methods: A retrospective review of clinical data and radiographs was conducted for patients with DD who had gait analysis before lower extremity skeletal surgery excluding foot procedures. Lower extremity range of motion was measured. The Pediatric Outcomes Data Collection Instrument (PODCI) was administered to parents to evaluate their children’s functional status. Gait laboratory data were collected to compare the hip and knee kinematics in cases with and without patellar dislocation. Anteroposterior standing radiographs were taken for all patients to assess the correlation between measurements (clinical, radiologic, and gait) for coronal knee alignment. Results: Thirty lower extremities of 15 children (7 females and 8 males) were evaluated. The mean age was 7.4±3 years, the mean height was 97.7±15 cm (z=−5.1), and the mean weight was 20.6±6.2 kg (z=−0.8). The DD PODCI subscores were statistically significantly lower (P<0.05) than the average stature for developing children, except for the happiness score. Gait analysis, compared between all DD and an age-normalized average stature group, showed decreased forward velocity, step length, and stride length with an increased average forward tilt of the trunk and pelvis, hip flexion, hip adduction, and internal rotation (P<0.001). Delta hip and knee motion were also decreased (P<0.001). The patella was dislocated in 19 (63.3%) and central in 11 (36.6%) knees. Comparison of the minimum knee and hip flexion at the stance phase demonstrated increased crouch gait in the patellar dislocation group (P<0.001). Knee alignment measurements between clinical examination and gait analysis showed moderate correlation (r, 0.476; P=0.008). Conclusions: Children with DD demonstrated lower PODCI subscores except for happiness. Gait analysis showed limited lower extremity function of the children with DD in our study group. Patella dislocation group had increased crouch gait. Levels of Evidence: Level III—diagnostic study.

Hip pathology in Majewski osteodysplastic primordial dwarfism type II.

Introduction: Majewski osteodysplastic primordial dwarfism type II (MOPDII) is characterized by severe prenatal and postnatal growth failure with microcephaly, characteristic skeletal dysplasia, an increased risk for cerebrovascular disease, and insulin resistance. MOPDII is caused by mutations in the pericentrin (PCNT) gene and is inherited in an autosomal-recessive manner. This study aimed to determine the incidence of hip pathology in patients with molecularly confirmed MOPDII and to describe the functional outcomes of surgical treatment. Methods: Thirty-three enrolled patients had a clinical diagnosis of MOPDII. Biallelic PCNT mutations or absent pericentrin protein was confirmed in 25 of these patients. Twelve patients (7 female) had appropriate clinical and radiographic records at this institution and were included in this study. The data collected included age at presentation, age at surgery, sex, body weight and height, weight-bearing status at diagnosis, and the clinical examination. Results: Four patients (31%) had coxa vara: 3 unilateral and 1 bilateral. Three unilateral patients had in situ pinning at a mean age 4 years. The patient with bilateral coxa vara had valgus osteotomy at the age of 5 years. Two children had bilateral hip dysplasia and subluxation with no surgery. One patient had bilateral developmental hip dislocations. The patient was treated by open reduction-spica cast and 2 years after surgery, coxa valga was noted. Another patient was diagnosed at an age of 12 years with bilateral avascular necrosis of the hips. Four patients did not have hip pathology. Conclusions: Hip pathology is common among children with MOPDII; coxa vara is the most frequent diagnosis. Routine clinical and radiographic hip evaluation is important. The capital femoral epiphysis appears to slip down along the shaft, giving the appearance of a proximal femoral epiphysiolysis. A hip diagnosed with slipped capital femoral epiphysis in early life may progress to severe coxa vara. Level of Evidence: Level IV.

A newly recognized syndrome with characteristic facial features, skeletal dysplasia, and developmental delay

We describe a series of seven male patients from six different families with skeletal dysplasia, characteristic facial features, and developmental delay. Skeletal findings include patellar dislocation, short tubular bones, mild metaphyseal changes, brachymetacarpalia with stub thumbs, short femoral necks, shallow acetabular roofs, and platyspondyly. Facial features include: a flattened midface with broad nasal bridge, cleft palate or bifid uvula and synophrys. All of the patients demonstrated pre‐school onset of a cognitive developmental delay with a shortened attention span. Some of the cognitive delay was masked by a warm and engaging personality. We posit that these individuals have a newly recognized syndrome characterized by the described features. There is some phenotypic overlap between these patients and Desbuquois dysplasia; however molecular testing demonstrated that this is a distinct disorder. Given the family information available for each patient, we are suspicious that the constellation of findings reported herein could be an X‐linked recessive syndrome.

Metatropic dysplasia—a skeletal dysplasia with challenging airway and other anesthetic concerns

Metatropic dysplasia is a rare form of skeletal dysplasia requiring multiple anesthetics for surgical and imaging procedures, most of which are orthopedic procedures. We provide centralized care to patients with skeletal dysplasia at our tertiary care pediatric hospital, and we were able to collect the largest number of metatropic dysplasia patients reported to date.