Search

We studied a family in which the first-born child, a girl, had developmental delay, facial dysmorphism, and agenesis of the corpus callosum (ACC). The subsequent pregnancy was interrupted as the fetus was found to be also affected by ACC. Both cases were heterozygous for two KDM5B variants predicting p (Ala635Thr) and p (Ser1155Ala fs Ter4) that were shown to be in trans . KDM5B variants have been previously associated with moderate to severe developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and dysmorphism in a few individuals, but the pathogenetic mechanisms are not clear yet as patients with both monoallelic and biallelic variants have been observed. Interestingly, one individual has previously been reported with ACC and severe ID in association with biallelic KDM5B variants. Together with the observations in this family, this suggests that agenesis of the corpus callosum may be part of the phenotypic spectrum associated with KDM5B variants and that the KDM5B gene should be included in gene panels to clarify the etiology of ACC both in the prenatal and postnatal setting.

Background: This report describes a new strategy for the care of patients with osteogenesis imperfecta, based on an interdisciplinary team working. Thereby, we aim at fulfilling three main goals: offering thorough coordinated management for all, and improving physical activity and quality of life of the patients., Aim: With rare diseases such as osteogenesis imperfecta (OI), patients and their family often suffer from inadequate recognition of their disease, poor care coordination and incomplete information. A coordinated interdisciplinary approach is one possible solution for providing both comprehensive and cost-effective care, with benefits for patient satisfaction. Poor physical activity and impaired quality of life represent a considerable burden for these patients. To better address these issues, in 2012 we created an interdisciplinary team for the management of OI patients in our University Hospital Centre (CHUV, Lausanne University Hospital,). In this article we describe the implementation of this interdisciplinary care strategy for patients suffering from OI, and its impact on their physical activity and quality of life., Methods: All patients from the French part of Switzerland were invited to join us. We proposed two complementary evaluations: the initial interdisciplinary evaluation and a yearly follow-up during a special day – the “OI day”. This day features specialised medical appointments adapted to each patient’s needs, as well as lectures and/or workshops dedicated to patients’ and families’ education. Our first aim was to propose for each patient the same management, from diagnosis to the bone health evaluation and physical therapy advice. Our second aim was to evaluate the evolution of physical activity, quality of life (measured by EQ-5D, SF-36 and a dedicated questionnaire) and satisfaction of patients and their families. Here we report both the initial and the long-term results., Results: Since 2012, 50 patients from the French part of Switzerland received the personalised medical evaluation. All of the patients included in this study had the same initial evaluation and at least one participation in an OI Day. All patients had an adaptation of their bone acting drugs. Over a 7-year period, 62% of inactive patients started some physical activity, and 44% of patients who were not involved in any athletic activity started participating in sports. The mean EQ-5D increased from 0.73 to 0.75 (p = 0.59). The mean physical SF36 (musculoskeletal function) score was 59.09 ± 22.72 and improved to 65.79 ± 21.51 (p = 0.08), whereas it was 68.06 ± 20.05 for the mental SF36 without alteration during follow-up. The OI day was revealed to be useful, it contributed to improvement in continuity of care and helped families to better understand the OI patients’ health., Conclusions: Our interdisciplinary approach aimed at offering the same thorough management for all patients from the French part of Switzerland, and at improving both the physical activity and the satisfaction of the patients and their family. This report is a basis for future work focusing on the effect of bone fragility and the impact of OI on patients’ social relations.

Cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome (MIM 600373) was first described and named by Shehib et al, in 1991 in a single patient. The anomalies referred to in the acronym are as follows: cerebral-developmental delay, ocular-cataracts, dental-aberrant cusp morphology and delayed eruption, auricular-malformations of the external ear, and skeletal-spondyloepiphyseal dysplasia. This distinctive constellation of anatomical findings should allow easy recognition but despite this only four apparently sporadic patients have been reported in the last 20 years indicating that the full phenotype is indeed very rare with perhaps milder or a typical presentations that are allelic but without sufficient phenotypic resemblance to permit clinical diagnosis. We performed exome sequencing in three patients (an isolated case and a brother and sister sib pair) with classical features of CODAS. Sanger sequencing was used to confirm results as well as for mutation discovery in a further four unrelated patients ascertained via their skeletal features. Compound heterozygous or homozygous mutations in LONP1 were found in all (8 separate mutations; 6 missense, 1 nonsense, 1 small in-frame deletion) thus establishing the genetic basis of CODAS and the pattern of inheritance (autosomal recessive). LONP1 encodes an enzyme of bacterial ancestry that participates in protein turnover within the mitochondrial matrix. The mutations cluster at the ATP-binding and proteolytic domains of the enzyme. Biallelic inheritance and clustering of mutations confirm dysfunction of LONP1 activity as the molecular basis of CODAS but the pathogenesis remains to be explored., (© 2015 Wiley Periodicals, Inc.)