Nosology and classification of genetic skeletal disorders: 2010 revision

Abstract

Genetic disorders involving the skeletal system arise through disturbances in the complex processes of skeletal development, growth and homeostasis and remain a diagnostic challenge because of their variety. The Nosology and Classification of Genetic Skeletal Disorders provides an overview of recognized diagnostic entities and groups them by clinical and radiographic features and molecular pathogenesis. The aim is to provide the Genetics, Pediatrics and Radiology community with a list of recognized genetic skeletal disorders that can be of help in the diagnosis of individual cases, in the delineation of novel disorders, and in building bridges between clinicians and scientists interested in skeletal biology. In the 2010 revision, 456 conditions were included and placed in 40 groups defined by molecular, biochemical, and/or radiographic criteria. Of these conditions, 316 were associated with mutations in one or more of 226 different genes, ranging from common, recurrent mutations to “private” found in single families or individuals. Thus, the Nosology is a hybrid between a list of clinically defined disorders, waiting for molecular clarification, and an annotated database documenting the phenotypic spectrum produced by mutations in a given gene. The Nosology should be useful for the diagnosis of patients with genetic skeletal diseases, particularly in view of the information flood expected with the novel sequencing technologies; in the delineation of clinical entities and novel disorders, by providing an overview of established nosologic entities; and for scientists looking for the clinical correlates of genes, proteins and pathways involved in skeletal biology. © 2011 Wiley-Liss, Inc.

Gain-of-function mutations in the phosphatidylserine synthase 1 (PTDSS1) gene cause Lenz-Majewski syndrome

“…No direct link has been established between phosphatidylserine metabolism and known pathways involved in skeletal dysplasias with increased bone density (especially the ones classified with LMS in group 24) 38 . Nevertheless, phosphatidylserine and its calcium-binding properties have been recognized as being important in bone mineralization, physiological and pathological calcification and dentine formation 39,40 .…”

Comprehensive genetic exploration of skeletal dysplasia using targeted exome sequencing

“…A recent update of the nosology and classification of genetic skeletal diseases included 40 groups and 456 disease entities, listing 226 causative genes that have been discovered for 316 diseases. 2 The clinical diagnosis of the specific disease entity causing skeletal dysplasia can be difficult for several reasons. First, individual clinicians have limited experience with these rare diseases.…”

Homozygous missense and nonsense mutations in BMPR1B cause acromesomelic chondrodysplasia-type Grebe

“…The severity of limb abnormalities increases in a proximo-to-distal gradient with hands and feet being most severely affected, showing brachydactyly and/or rudimentary fingers. The group of ACDs are classified into five subgroups according to the Nosology and Classification of Genetic Skeletal Disorders: 2 Acromesomelic dysplasia-type Maroteaux (MIM 602875), Grebe dysplasia (Grebe type, MIM 200700 and Hunter Thompson type, MIM 201250), Fibular hypoplasia and complex brachydactyly (Du Pan, MIM 228900), acromesomelic dysplasia with genital anomalies (MIM 609441) and Acromesomelic dysplasia Osebold-Remondini type (MIM 112910). Grebe dysplasia and Du Pan syndrome share an autosomal recessive inheritance pattern and are caused by homozygous or compound heterozygous mutations in growth and differentiation factor 5 (GDF5; MIM *601146).…”