Best practice guidelines regarding diagnosis and management of patients with type II collagen disorders

Abstract

on behalf of the Skeletal Dysplasia Management Consortium Purpose: Skeletal dysplasias comprise a heterogeneous group of inherited disorders of development, growth, and maintenance of the human skeleton. Because of their relative rarity and wide phenotypic variability, patients should be accurately identified, uniformly assessed, and managed by clinicians who are aware of their potential complications and possess the knowledge and resources to treat them effectively. This study presents expert guidelines developed to improve the diagnosis and management of patients with type II collagen skeletal disorders to optimize clinical outcomes. Methods: A panel of 11 multidisciplinary international experts in the field of skeletal dysplasia participated in a Delphi process, which comprised analysis of a thorough literature review with subsequent generation of 26 diagnosis and care recommendations, followed by two rounds of anonymous voting with an intervening face-to-face meeting. Those recommendations with more than 80% agreement were considered as consensual. Results: After the first voting round, consensus was reached to support 12 of 26 (46%) statements. After the panel discussion, the group reached consensus on 22 of 24 revised statements (92%). Conclusions: Consensus-based, expert best practice guidelines developed as a standard of care to assist accurate diagnosis, minimize associated health risks, and improve clinical outcomes for patients with type II collagen skeletal dysplasias.

Best Practice Guidelines in Managing the Craniofacial Aspects of Skeletal Dysplasia

“…OPD type II represents the more severe form of the disorder and is typically lethal in infancy. 3,64 Cleft palate abnormalities occur in approximately one-third of patients with diastrophic dysplasia and have been reported in association with Robin sequence in other SLC26A2 disorders, including recessive multiple epiphyseal dysplasia (rMED). 65,66 The specialized needs in the treatment of palate abnormalities in the individuals, compounded with the rarity of these conditions, cannot be over emphasized.…”

“…Similarly, palate abnormalities with or without Robin sequence are more prevalent in certain types of skeletal dysplasia. Speci c to skeletal dysplasia, pathogenic variants in genes encoding type II and XI collagen (COL2A1, COL11A1 and COL11A2), Filamin-A (FLNA), and the diastrophic sulfate transport protein (SLC26A2) are all well-known as being associated with cleft palate.Recognized skeletal phenotypes of type II collagen disorders include (from most to least severe): achondrogenesis type II, hypochondrogenesis, Kniest dysplasia, spondyloepiphyseal dysplasia congenita (SEDC), Stickler syndrome type I, and mild SED with premature arthrosis 3,58. Cleft palate is a major feature of SEDC59,60,61 , but is found in all forms of type II collagen disorders, either alone or as part of Robin sequence.…”

Best practice guidelines in managing the craniofacial aspects of skeletal dysplasia

“…Craniofacial anomalies, clefts of the palate, structural changes of the upper and lower jaws, and static and dynamic laryngotracheal disease can all contribute to airway obstruction when awake and/or sleeping. For example, those with type II collagen disorders can have tracheomalacia that can further compound anatomically smaller airways 3 .…”

Best practice guidelines for management of spinal disorders in skeletal dysplasia

“…Spinal disorders include kyphosis, scoliosis, central stenosis, vertebral instability and hyperlordosis, often resulting in neurologic decompensation. Their presentation can be extremely variable within and between different types of skeletal dysplasia, for example in disorders of type II collagen [7].…”

“…Many types of skeletal dysplasia also have hypoplasia of the odontoid process with associated craniocervical instability [17]. Some skeletal dysplasia are suspected antenatally on ultrasound findings, which can be further delineated by prenatal MRI [7].…”