Post-mortem histology in transient receptor potential cation channel subfamily V member 6 (TRPV6) under-mineralising skeletal dysplasia suggests postnatal skeletal recovery: a case report.

BACKGROUND: The calcium-selective channel TRPV6 (transient receptor potential cation channel subfamily V member 6) is crucial for maternal-fetal calcium transport across the placenta. TRPV6 mutations have recently been associated with an antenatally severe under-mineralising skeletal dysplasia accompanied by postnatal biochemical abnormalities. This is the first post-mortem report in a patient with TRPV6 skeletal dysplasia. CASE PRESENTATION: The female infant had severe antenatal and postnatal skeletal abnormalities by 20 weeks gestation and was ventilator-dependent from birth. These skeletal abnormalities were apparent at an earlier gestational age than in previous reported cases and a more severe clinical course ensued. Biochemical and skeletal abnormalities, including bone density, improved postnatally but cardiac arrest at 4 months of age led to withdrawal of intensive care. Compound heterozygous TRPV6 variants (c.1978G > C p.(Gly660Arg) and c.1528C > T p.(Arg510Ter)) were identified on exome sequencing. Post-mortem identified skeletal abnormalities but no specific abnormalities in other organ systems. No placental pathology was found, multi-organ histological features reflected prolonged intensive care only. Post-mortem macroscopic examination indicated reduced thoracic size and short, pale and pliable ribs. Histological examination identified reduced number of trabeculae in the diaphyses (away from the growth plates), whereas metaphyses showed adequate mineralisation and normal number of trabeculae, but with slightly enlarged reactive chondrocytes, indicating post-natal skeletal growth recovery. Post-mortem radiological findings demonstrated improved bone density, improved rib width, healed fractures, although ribs were still shorter than normal. Long bones (especially humerus and femur) had improved from initial poorly defined metaphyses and reduced bone density to sharply defined metaphyses, prominent growth restart lines in distal diaphyses and bone-in-bone appearance along diaphyses. CONCLUSIONS: This case provide bone histological confirmation that human skeletal development is compromised in the presence of TRPV6 pathogenic variants. Post-mortem findings were consistent with abnormal in utero skeletal mineralisation due to severe calcium deficit from compromised placental calcium transfer, followed by subsequent phenotypic improvement with adequate postnatal calcium availability. Significant skeletal recovery occurs in the early weeks of postnatal life in TRPV6 skeletal dysplasia.

Five-year follow-up outcomes of comprehensive rehabilitation in Korean siblings with cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome: A case report.

RATIONALE: Cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome is a very rare multisystem disorder, which shows malformations of the central nervous system, ears, eyes, teeth, and skeleton that was first reported in 1991. Only a few cases that sporadically occurred have been reported worldwide. The research investigating the pathogenesis and patterns of CODAS inheritance is still ongoing. There is no satisfactory treatment for this rare genetic disease yet. Due to the lack of curative medical treatment, rehabilitation could play a major role in treatment for genetic disease. PATIENT CONCERNS: To our best knowledge, the 2 children described in this study are the only CODAS syndromes siblings reported in the world so far. These Korean siblings show highly distinctive features consisting of developmental delay, cataracts, vulnerability to tooth decay, epiphyseal dysplasia, and anomalous ears. DIAGNOSES: CODAS syndrome. INTERVENTIONS: Comprehensive long-term rehabilitation treatment during 5 years. OUTCOMES: We report on the progress of the comprehensive long-term rehabilitation treatment at 5-year follow-up. Their fine motor and language skills development improved similarly to that of same-aged children. We observed the positive effect of rehabilitation on the quality of life. LESSONS: The therapy of genetic disorders is challenging for pediatric neurologists and pediatric physiatrists. We suggest that rehabilitation is the best treatment currently available for this genetic disease that yields satisfactory therapeutic effect.

Long-term follow-up of a Schwartz-Jampel syndrome case.

Schwartz-Jampel syndrome (SJS) is a rare genetic disorder characterised by myotonia and bone dysplasia. It is inherited as an autosomal recessive trait and caused by mutations in the perlecan-encoding gene HSPG2. Its symptoms include muscular stiffness and hypertrophy. The aim of the study was to analyse the clinical presentation as well as the physical therapy and rehabilitation in a patient with SJS. A 20-year-old male patient with SJS was followed up by the authors for the past 3 years. The paper assesses the physical therapy and rehabilitation conducted at home and presents the possibilities of an extended programme that can be implemented at the multi-field Division of Physical Medicine. Patients with SJS represent an extremely difficult clinical and therapeutic problem.

Measures of self-care independence for children with osteochondrodysplasia: a clinimetric review.

This systematic review evaluates the validity, reliability, and clinical utility of outcome measures used to assess self-care skills among children with congenital musculoskeletal conditions and assesses the applicability of these measures for children with osteochondrodysplasia aged 0-12 years. Electronic databases were searched to identify self-care assessments that addressed the self-care domain as defined by of the International Classification of Function Disability and included children with osteochondrodysplasia. Ten measures were identified and three met the inclusion criteria: the Functional Independence Measure for Children (WeeFIM), the Activities Scale for Kids (ASK), and the Pediatric Evaluation of Disability Inventory (PEDI). Although psychometric data specific to children with osteochondrodysplasia are limited, adequate to excellent reliability and evidence of validity were reported for all three instruments for children with physical disabilities. Further evaluation of psychometric properties of self-care instruments specifically for children with osteochondrodysplasia would be beneficial to help identify instruments that will assist with improved assessment and management.

Jarcho-Levin syndrome: a case study.

Jarcho-Levin syndrome is a rare genetic disorder characterized by multiple vertebral and rib anomalies. There are two types of Jarcho-Levin syndrome, spondylothoracic dysplasia and spondylocostal dysostosis. Spondylothoracic dysplasia has a grimmer prognosis than spondylocostal dysostosis. Many of the infants born with this disorder succumb to respiratory failure. With new advances in medical care, even the more severely affected children have an improved chance of survival. This is a case presentation of one child with spondylothoracic dysplasia and a brief history of the disease process.

Spondyloepiphyseal dysplasia congenita with ventilator dependence: two case reports.

Home mechanical ventilation has recently become feasible in a number of conditions. Several small series and case reports mention respiratory insufficiency or failure in a subset of patients with spondyloepiphyseal dysplasia congenita. Two cases of successful home mechanical ventilation in children, now 7 years of age, who have spondyloepiphyseal dysplasia congenita and respiratory insufficiency, are reported. Novel rehabilitation planning has facilitated the growth and development of these children.