Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Prosodic features of maternal input to children with sex chromosome trisomies

The neuropsychological profile associated with sex chromosome trisomies (SCT) is frequently characterised by delays or deficits in linguistic development. Although maternal input could have an important role in influencing and shaping the linguistic development of children with SCT, there is a lack of studies in the literature that have investigated its prosodic characteristics. The study aims to analyse the prosodic features of the maternal input addressed to a group of 8-month-old children with SCT and a group of typically developing (TD) peers. Nineteen mother-child dyads with children with SCT and 19 mother-child dyads with TD children participated in the study. Maternal utterances were collected during video-recorded play sessions, and for each dyad, 50 maternal utterances were selected and analysed using the software Praat. The results showed that the maternal input produced by the mothers in the SCT group was characterised by a significantly lower pitch, less marked and modulated melodic contours, and a shorter final syllable duration than the input addressed to TD children. The prosodic features found in the maternal input addressed to children with SCT were not those expected in the maternal input addressed to children at this developmental stage and could create a non-optimal linguistic environment

Speech Sound Development in 18-Month-Old Children With Sex Chromosome Trisomies

Purpose: This study aimed to describe speech sound development in a group of 18-month-old children with sex chromosome trisomies (SCTs), compared with a group of typically developing (TD) peers. Concurrent and longitudinal relationships between speech sound abilities and lexical development were examined. Method: A group of 76 children aged 18 months, 38 children prenatally diagnosed with SCTs (12 with XXY, 12 with XYY, and 14 with XXX) and 38 TD children, participated in the study. From video recordings of semistructured naturalistic parent-child play sessions, quantitative and qualitative measures of speech sound development were collected (e.g., the number of consonants, type and place of articulation, and syllable structures used), and group differences were observed. The relationships between the number of consonants produced and vocabulary size at 18 and 24 months were assessed. Results: At 18 months, children with SCTs used a significantly lower number of consonants than TD children. Qualitatively, children with SCTs used significantly fewer articulatory complex consonants (fricative/affricates) and a more restricted inventory of syllable structures. The number of consonants used was significantly correlated with lexical development at 18 months. Moreover, in the SCTs group (but not in the TD group), the children with lower speech sound development at 18 months showed a significantly smaller vocabulary growth between 18 and 24 months than those with higher speech-sound development. Conclusions: Toddlers with SCTs showed a significantly delayed speech sound development pattern rather than an atypical one. Children with SCTs with low speech sound development also showed lower vocabulary growth between 18 and 24 months of age. These results can be clinically relevant for follow-up and treatment planning for children with SCTs

Phenotype and genotype of 87 patients with Mowat-Wilson syndrome and recommendations for care

Purpose: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS. Methods: In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neuro-developmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations. Results: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. Conclusion: Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care