A novel COL2A1 mutation causing spondyloepiphyseal dysplasia congenita in a Chinese family.

BACKGROUND: Spondyloepiphyseal dysplasia congenita is an autosomal dominant cartilaginous dysplasia characterized by short trunk, abnormal epiphysis, and flattened vertebral body. Skeletal features of SEDC are present at birth and evolve over time. Other features of SEDC include myopia and/or retinal degeneration with retinal detachment and cleft palate. A mutation in the COL2A1 gene located in 12q13.11 is considered as one of the important causes of SEDC. In 2016, Barat-Houari et al. reported a large number of COL2A1 mutations. Among them, a non-synonymous mutation in COL2A1 exon 37, c.2437G>A (p. Gly813Arg), has been reported to cause SEDC in only one patient from France so far. METHODS: We followed up a patient with SEDC phenotype and his family members. The clinical manifestations, physical examination and imaging examination, including X-ray, CT and MRI, were recorded. The whole-exome sequencing was used to detect the patients' genes, and the pathogenic genes were screened out by comparing with many databases. RESULTS: We report a Chinese patient with SEDC phenotype characterized by short trunk, abnormal epiphysis, flattened vertebral body, narrow intervertebral space, dysplasia of the odontoid process, chicken chest, scoliosis, hip and knee dysplasia, and joint hypertrophy. Gene sequencing analysis showed that the patient had a heterozygous mutation (c.2437G>A; p. Gly813Arg) in the COL2A1 gene. No COL2A1 mutation or SEDC phenotype was observed in his family members. This is the first report of SEDC caused by this mutation in an East Asian family. CONCLUSION: This report provides typical clinical, imaging, and genetic evidence for SEDC, confirming that a de novo mutation in the COL2A1 gene, c.2437G>A (p. Gly813Arg), causes SEDC in Chinese population.

Total Hip Arthroplasty Reduces Pain and Improves Function in Patients With Spondyloepiphyseal Dysplasia: A Long-Term Outcome Study of 50 Cases.

BACKGROUND: Spondyloepiphyseal dysplasia (SED) is rare genetic condition which leads to skeletal and joint deformities that can predispose patients to degenerative joint disease. There are limited reports on the results of total hip arthroplasty (THA) in this patient population. The purpose of this study is to review clinical and radiographic outcomes of THA performed in patients with SED at one institution. METHODS: Among 43,917 patients undergoing primary THA from 1970 to 2015, we identified 50 THAs performed in 29 patients with SED; 21 patients underwent bilateral THA (none simultaneous). There were 16 females and 13 males; mean age, body mass index, and height were 39 years, 28.7 kg/m2, and 145 cm, respectively. All patients were able to ambulate prior to the THA. Mean follow-up was 11 years (range 2-38). RESULTS: Mean implant survival for primary THA in SED patients at the 5, 10, and 20-year time points was 96%, 85%, and 55%, respectively. Thirteen patients required revision THA, most commonly for polyethylene wear (n = 6) and aseptic loosening (n = 5), and 4 additional patients underwent nonrevision reoperations. Prior to surgery, 90% of patients had severe or moderate pain, which was reduced to 8% of patients postoperatively (P < .001). Mean Harris Hip Score improved from 47 to 87 (P < .001). Prior to surgery, 64% of patients required gait aids, which reduced to 34% postoperatively (P < .001). CONCLUSION: THA provided significant pain reduction and improvement in function, with a majority of patients ambulating independently following the procedure. There was a high incidence of complications following THA in patients with SED, most commonly secondary to polyethylene wear and osteolysis from conventional polyethylene and historical implants. LEVEL OF EVIDENCE: Level IV, Therapy.

Cervical Spine Injury From Unrecognized Craniocervical Instability in Severe Pierre Robin Sequence Associated With Skeletal Dysplasia.

Pierre Robin Sequence (PRS) can be associated with skeletal dysplasias, presenting with craniocervical instability and devastating spinal injury if unrecognized. The authors present the case of an infant with PRS and a type II collagenopathy who underwent multiple airway-securing procedures requiring spinal manipulation before craniocervical instability was identified. This resulted in severe cervical cord compression due to odontoid fracture and occipitoatlantoaxial instability. This case highlights the importance of early cervical spine imaging and cautious manipulation in infants with PRS and suspected skeletal dysplasia.

Mandibular Distraction in a Patient With Type II Collagenopathy.

Kniest dysplasia is an extremely rare form of type II collagenopathy associated with cleft palate, micrognathia, shortened trunk, arms and legs, and club foot. The authors present a case of an infant with this disorder who also had micrognathia and respiratory distress for which mandibular distraction was performed. Although abnormal collagen and impaired endochondral ossification is noted with Kniest dysplasia, adequate bone formation was observed across the distraction gap. Nonetheless, despite stable mandibular advancement, failure to consider concomitant restrictive lung disease resulted in tracheostomy dependence. The authors demonstrate that while successful bone regeneration can be achieved through distraction of intramembranous facial bones, discretion must still be employed in patients with collagenopathies.

Clinical Experience of Treatment of Facial Malformations in Oto-Palato-Digital Syndrome: A Familial Patient.

Oto-palato-digital syndrome type 1 (OPD1) is an X-linked recessive disorder comprising characteristic facial appearances and skeletal alterations. The authors report OPD1 in a mother and her 2 sons who had multiple common congenital anomalies. Both of the brothers were born with mild hearing impairment, frontal bossing with prominent supraorbital ridges, downslanting palpebral fissures, dental malocclusion, and palatal clefts. They underwent a series of aesthetic surgeries for their facial malformations with good cosmetic results. The mother had a milder phenotype with less prominent craniofacial defects that did not require surgical correction. The older brother required a 2-jaw surgery whereas the younger brother required a surgically assisted rapid palatal expansion. In the second series of operations, both brothers underwent scraping of their prominent supraorbital ridge. They have been free of complications throughout their 16-year follow-up. The authors also screened the family for possible genetic etiologies and identified mutations in the causative gene of OPD1 on Xq28 in all 3 patients. In conclusion, the authors have identified 3 patients with OPD1, performed surgical treatments on the affected brothers and have obtained good reconstructive results. There are no reports involving OPD1 patients who have received good surgical treatment. With careful examination and identification of patients with characteristic facies and skeletal abnormalities, it is our opinion that the authors can help more patients with this disease through surgical management.

Anterior mediastinal tracheostomy with a median mandibular splitting approach in a Larsen syndrome patient with posterior cervical arthrodesis.

Larsen syndrome is a rare congenital connective tissue disorder characterized by multiple joint dislocations. A novel anterior mediastinal tracheostomy with a median mandibular splitting approach is presented for the treatment of airway obstruction in a Larsen syndrome patient with posterior cervical arthrodesis.

Fast and early mandibular osteogenetic distraction in a 24-day-old female newborn with Larsen syndrome.

BACKGROUND: Larsen syndrome (LS) is a rare bone dysplasia characterized by multiple dislocations affecting large and small joints, progressive scoliosis, accessory and early ossifying carpal/tarsal bones, and characteristic craniofacial features. CASE PRESENTATION: A newborn with a clinical diagnosis of LS is presented. Shortly after birth, she had respiratory distress due to retrognathia. Such a life-threatening complication was resolved by mandibular distraction osteogenesis at 24 days of age. CONCLUSION: Fast and early mandibular osteogenetic distraction could represent an optimal tool to avoid tracheostomy and to improve oral feeding in patients with rare conditions, such as LS.

Identification of novel homozygous nonsense SLC10A7 variant causing short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis and surgical management of spine.

BACKGROUND: Short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis is a rare, autosomal recessive, skeletal disorder first described in 2018. This syndrome starts with pre- and postnatal developmental delay, and gradually presents with variable facial dysmorphisms, a short stature, amelogenesis imperfecta, and progressive skeletal dysplasia affecting the limbs, joints, hands, feet, and spine. CASE PRESENTATION: We identified a homozygous novel nonsense mutation in exon 1 of SLC10A7 (NM_001300842.2: c.100G > T / p.Gly34*) segregating with the typical disease phenotype in a Han Chinese family. We reviewed the 12-year surgical treatment history with seven interventions on spine. CONCLUSION: To date, only 12 cases of the SLC10A7 mutation have been reported, mainly from consanguineous families. Our patient showed a relatively severe and broad clinical phenotype compared with previously reported cases. In this patient, annual check-ups and timely surgeries led to a good outcome.

Multidisciplinary approach to the treatment of a patient with chondrodystrophic myotonia (Schwartz-Jampel vel Aberfeld syndrome): case report and literature review.

Chondrodystrophic myotonia, Schwartz-Jampel syndrome, is a rare congenital disorder, which results from disturbance in a perlecan protein synthesis. Most affected are the muscles, acting in generalized myotonia, leading to joint contractures, weird-looking mask-like face appearance, and causing vision disturbances. Also, impaired bones and cartilages result in skeletal anomalies and dental disorders. Allergic reactions to numerous drugs occur in affected individuals. Surgical treatment is risky, due to a low tolerance of anesthetics and high risk of malignant hyperthermia. In this article, a case of 17-year-old girl with Schwartz-Jampel syndrome is presented. The patient with typical syndrome debilitations underwent long diagnostic scheme and multiple treatments in order to restore acceptable appearance and function. All procedures were performed with cautious anesthesiologists' supervision. Modern diagnostic tools can improve the diagnosis rate while multidisciplinary evaluation and advanced treatment techniques can reveal symptoms, minimizing the hazard of anesthesia and improving the quality of life.

The Managment of cervical spine abnormalities in children with spondyloepiphyseal dysplasia congenita: Observational study.

Spondyloepiphyseal dysplasia congenita (SEDC) is an autosomal dominant disorder, characterized by disproportionate dwarfism with short spine, short neck associated with variable degrees of coxa vara. Cervical cord compression is the most hazardous skeletal deformity in patients with SEDC which requires special attention and management.Ten patients with the clinical and the radiographic phenotypes of spondyloepiphyseal dysplasia congenita have been recognized and the genotype was compatible with single base substitutions, deletions or duplication of part of the COL2A1 gene (6 patients out of ten have been sequenced). Cervical spine radiographs showed apparent atlantoaxial instability in correlation with odontoid hypoplasia or os-odontoideum.Instability of 8 mm or more and or the presence of symptoms of myelopathy were the main indications for surgery. Posterior cervical fusion from the occiput or C1-3, decompression of C1-2 and application of autorib transfer followed by halo vest immobilization have been applied accordingly.Orthopedic management of children with spondyloepiphyseal dysplasia congenita (SEDC) should begin with the cervical spine to avoid serious neurological deficits and or mortality.

Orthognathic surgery in Melnick-Needles syndrome: a review of the literature and report of two siblings.

Melnick-Needles syndrome (MNS) is a rare congenital X-linked dominant skeletal dysplasia, characterized by exophthalmos, a prominent forehead, and mandibular hypoplasia and retrognathism. Dental features may include anodontia, hypodontia, or oligodontia. Increased collagen content, unpredictable collagen synthesis, and abnormal bony architecture have raised concerns regarding bone splitting intraoperatively and bone healing postoperatively. This report describes the cases of two sisters with MNS, who successfully underwent orthognathic surgery consisting of bilateral mandibular ramus osteotomies combined with advancement genioplasty and iliac crest bone grafting, to correct the classical MNS facial deformity of mandibular retrognathia.

Airway stenting in a child with spondyloepiphyseal dysplasia congenita: 13-Year survival.

We describe the case of a boy with spondyloepiphyseal dysplasia congenita. At birth, he experienced severe respiratory distress necessitating tracheotomy. Endoscopy done because mechanical ventilation failed to resolve desaturations disclosed severe tracheo-bronchomalacia. A Polyflex silicone stent was placed in the trachea (replaced by Y-Dumon stent) and 2 Palmaz metallic stents in the mainstem bronchi (overlapped with 2 Jomed stents 5 years later). Airway stenting guaranteed a suitable respiratory status and allowed a child who was expected to die at birth, to reach 13.5 years old in good conditions.

Surgery of the head and neck in patient with Kniest dysplasia: Is wound healing an issue?

Kniest dysplasia is a type II collagen disorder that arises from a genetic mutation of the COL2A1 gene that results in short stature, midface anomalies, tracheomalacia, and hearing loss. Disruption of the normal collagen pathway can lead to many changes given its critical role in the body, and can cause complications with respect to wound healing. We present a case in which a patient with Kniest dysplasia successfully underwent multiple procedures in the head and neck region including cochlear implantation, mandibular distraction, palatoplasty, and laryngotracheal reconstruction. All procedures did not have any associated complications with respect to wound healing, indicating that surgery in this population can take place as indicated and surgery should not be contraindicated or delayed.

Orthopaedic manifestations and management of spondyloepimetaphyseal dysplasia Strudwick type.

Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type is a rare autosomal dominant condition arising from defects in COL2A1 the genes responsible for the biosynthesis of procollagen type II. The orthopaedic manifestations of patients can be hypoplastic odontoid peg with atlantoaxial instability, severe kyphosis or lordosis of dorsal and lumbar spines, hip subluxation, coxa vara and early severe hip osteoarthritis, and malalignment of lower limbs like genu valgum or club foot. We report a mother and daughter with SEMD Strudwick Type and describe their orthopaedic problems, surgical management and clinical outcome after 30 years and 7 years of follow-up respectively.

Stabilization of the cervical spine in spondyloepiphyseal dysplasia congenita.

Spondyloepiphyseal dysplasia congenita is an inheritable bone dysplasia causing abnormalities that manifest at birth and primarily involve the spine and proximal epiphyses. The clinical findings include short-trunk dwarfism, myopia, frequent retinal detachment, shortening of the spine and proximal extremities, mild thoracic kyphoscoliosis, a barrel-shaped thorax, a short neck, and mild ocular hypertelorism. The characteristic radiographic features are a generalized delay in ossification, flattening and dysplasia of the vertebral bodies, pelvic dysplasia, and retarded ossification of the femoral head and neck. Other radiographic features of interest to the neurosurgeon may be platybasia, kyphoscoliosis, lumbar hyperlordosis, and odontoid hypoplasia. A case of spondyloepiphyseal dysplasia congenita is presented in which an unstable and markedly dysplastic cervical spine was stabilized with Halifax interlaminar clamps and sublaminar wires. The clinical findings and radiographic features are presented and the etiology and neurosurgical management of spondyloepiphyseal dysplasia congenita are discussed.

[Anesthetic management of a child with Schwartz-Jampel syndrome].

A 6-year-old child with Schwartz-Jampel syndrome (SJS) underwent tenotomy of bilateral lower limbs under general anesthesia. Patient with SJS has problems such as difficulty of intubation owing to microstomia and jaw muscle rigidity, and is susceptible to malignant hyperthermia by using volatile inhalation anesthetics. In this case, we used a laryngeal mask for airway management and anesthesia was maintained with inhalation of nitrous oxide and continuous i.v. infusion of propofol with caudal block, and his clinical course was uneventful.

Neurosurgical interventions for spondyloepiphyseal dysplasia congenita: clinical presentation and assessment of the literature.

BACKGROUND: Spondyloepiphyseal dysplasia (SED) is a rare disease that causes vertebral abnormalities and short-trunk dwarfism. The two forms of SED are congenita and tarda. Each form arises in a genetically distinct fashion and manifests with a different set of complications. SED congenita is more severe, and patients usually display atlantoaxial instability and odontoid hypoplasia. Patients often have various neurologic deficits caused by compression of the spinal cord. The region most affected is the craniovertebral junction (CVJ). METHODS: A review of the PubMed Database, 1970 to the present, was performed using the search term "spondyloepiphyseal dysplasia" and limited to English-language articles. The search identified 22 articles discussing COL2A1 gene mutations and 10 clinical articles describing patients with SED and associated spinal abnormalities. RESULTS: Findings from the literature concerning diagnosis, presenting symptoms, and intervention taken are discussed. Additionally, a patient with a diagnosis of SED congenita who presented with bilateral hand numbness is described. The patient underwent a suboccipital craniotomy; posterior decompression of the foramen magnum, the arch of C1, and the lamina of C2; and instrumented fusion of C1-3 to relieve his symptoms. CONCLUSIONS: In this article, the authors survey the current literature surrounding neurosurgical interventions and present an algorithm for treatment.

Larsen syndrome with C3-C4 spondyloptosis and atlantoaxial dislocation in an adult.

STUDY DESIGN: This is a clinical case report with a review of relevant literature. OBJECTIVE: To describe a case of Larsen syndrome with C3-C4 spondyloptosis and atlantoaxial dislocation in a middle-aged female patient and to discuss management strategies. SUMMARY OF BACKGROUND DATA: Spondyloptosis of the cervical spine is relatively rare and is caused by trauma, destruction of the vertebral bodies by tumors, or tuberculosis. Such gross vertebral displacement is usually associated with significant neurological deficits. Larsen syndrome is characterized by multiple joint displacements and can, very rarely, be associated with nontraumatic spondyloptosis of the cervical vertebra. A single case report of C1-C2 joint laxity causing atlantoaxial dislocation in a patient with Larsen syndrome is available in literature. No reports of any patient (with Larsen syndrome or nonsyndromic) who had both cervical spondyloptosis and atlantoaxial dislocation are available in literature. METHODS: A 36-year-old female presented with chronic neck pain, bilateral hand deformity, and mild spasticity involving all 4 limbs. Cervical radiograph, computed tomographic scan, and magnetic resonance image revealed C3-C4 spondyloptosis and atlantoaxial dislocation. RESULTS: A combined ventral decompression of subaxial spine and instrumentation from C2 to C5, followed by posterior C1-C2 distraction arthroplasty and lateral mass stabilization of the subaxial spine up to C6, was done. The cervical deformity was corrected, and the patient remains symptom free. CONCLUSION: Patients with spondyloptosis of the cervical spine can rarely present with chronic neck pain and minimal neurological deficits. An additional pathology, such as atlantoaxial dislocation, can add to the complexity. Circumferential stabilization and fusion would be required in such cases to achieve a good outcome. Larsen syndrome is a rare cause of nontraumatic cervical displacements.

Orthognathic surgery in Melnick-Needles-Syndrome. Case report and review of the literature.

Melnick-Needles Syndrome (MNS) is a congenital syndrome associated with severe architectural disorder of the skeletal system that can cause significant effects on the craniofacial skeleton including poor aesthetics, impaired speech and masticatory problems. The authors report a case of a female patient who experienced masticatory constraint, hindered speech and functional problems related to a severe bite dysfunction due to the mandibular hypoplasia and the underlying bony architectural disorder associated with MNS. The patient underwent bilateral sagittal split osteotomy (BSSO) to correct her skeletal malocclusion and improve the characteristic aesthetics and speech. The inherent bony abnormalities with their altered collagen structure presented unique challenges to orthognathic surgery in this patient with an unpredictable bone healing process. In MNS patients a fragile trabecular bone structure and an increased bleeding tendency is thought to delay or forestall wound healing. The patient was treated successfully with BSSO and monocortical plate fixation following a well-established algorithm from orthodontic preparation to surgical protocol. A very satisfying outcome has been achieved, concerning functional rehabilitation and aesthetic improvement. A review of the literature revealed that little is known about bone regeneration and fracture healing in cases with MNS.