A reassessment of Jackson\u2019s checklist and identification of two Down syndrome sub-phenotypes

Chiara Locatelli,Giuseppe Ramacieri,Sara Onnivello,Chiara Marcolin,Silvia Lanfranchi,Pierluigi Strippoli,Beatrice Vione,Francesca Antonaros,Allison Piovesan,Guido Cocchi,Maria Chiara Pelleri,Francesca Pulina,Renzo Vianello,Maria Caracausi,Luigi Corvaglia,Gian Luca Pirazzoli,Caterina Gori,Lorenza Vitale

doi:10.1038/s41598-022-06984-0

Chiara Locatelli, Giuseppe Ramacieri + Show 16 more

Open Access

https://doi.org/10.1038/s41598-022-06984-0

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Abstract

Down syndrome (DS) is characterised by several clinical features including intellectual disability (ID) and craniofacial dysmorphisms. In 1976, Jackson and coll. identified a checklist of signs for clinical diagnosis of DS; the utility of these checklists in improving the accuracy of clinical diagnosis has been recently reaffirmed, but they have rarely been revised. The purpose of this work is to reassess the characteristic phenotypic signs and their frequencies in 233 DS subjects, following Jackson's checklist. 63.77% of the subjects showed more than 12 signs while none showed less than 5, confirming the effectiveness of Jackson's checklist for the clinical diagnosis of DS. An association between three phenotypic signs emerged, allowing us to distinguish two sub-phenotypes: Brachycephaly, short and broad Hands, short Neck (BHN), which is more frequent, and "non-BHN". The strong association of these signs might be interpreted in the context of the growth defects observed in DS children suggesting decreased cell proliferation. Lastly, cognitive assessments were investigated for 114 subjects. The lack of association between the presence of a physical sign or the number of signs present in a subject and cognitive skills disproves the stereotype that physical characteristics are predictive of degree of ID.

Highlights

Down syndrome (DS) is characterised by several clinical features including intellectual disability (ID) and craniofacial dysmorphisms
A reassessment of the characteristic phenotypic signs in all subjects with DS was performed following the more comprehensive feature list proposed for the DS clinical diagnosis[11,12]
The first objective was to analyse in depth the DS phenotypic characteristics and its presentation patterns following the so-called Jackson’s c hecklist[12] in order to assess the reliability of the clinical diagnosis and lead to a deeper understanding of the syndrome

Summary

Introduction

Down syndrome (DS) is characterised by several clinical features including intellectual disability (ID) and craniofacial dysmorphisms. Down syndrome (DS) or trisomy 2 11 is defined by the presence of an extra full or partial copy of chromosome 212 It is the most common human chromosomal disorder and the leading genetic cause of intellectual disability (ID), with an incidence of 1 in ~ 800 live b irths[3]. After visiting 48 newborns with DS, Hall was the first who identified 10 cardinal signs for clinical diagnosis which are easy to assess and occur in over 40% of affected infants. They are unusual in non-DS infants and the same defect is always manifested in the same way. The diffusion of this checklist is an excellent way to bring attention to the clinical and phenotypic signs of DS contributing to a better understanding of the role of the excess chromosome 21

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