Stüve-Wiedemann Syndrome: Update on Clinical and Genetic Aspects.

Stüve-Wiedemann syndrome is a rare autosomal recessive disorder characterized by bowed long bones, joint restrictions, dysautonomia, and respiratory and feeding difficulties, leading to death in the neonatal period and infancy in several occasions. Since the first cases in 1971, much has been learned about this condition, including its molecular basis - mutations in the leukemia inhibitory factor receptor gene (LIFR) -, natural history and management possibilities. This review aims to highlight the clinical aspects, radiological features, molecular findings, and management strategies in Stüve-Wiedemann syndrome.

Intragenic Deletion in the LIFR Gene in a Long-Term Survivor with Stüve-Wiedemann Syndrome.

Stüve-Wiedemann syndrome (SWS, OMIM 601559) is a rare autosomal recessive bent-bone dysplasia, caused by loss-of-function mutations in the leukemia inhibitory factor receptor (LIFR) gene, which usually leads to early death. Only few patients with long-term survival have been described in the literature. We report on a 5-year-old boy from a consanguineous marriage with molecular analysis for the LIFR gene. Sanger and next-generation sequencing (NGS) of LIFR were performed. Copy number variation analysis with NGS showed a novel mutation as the cause for the syndrome: an intragenic homozygous deletion in LIFR, involving exons 15-20. Bridging PCR was carried out to confirm the intragenic deletion. This is the first description of a large deletion in LIFR, broadening the spectrum of mutations in SWS. Besides the reported allelic heterogeneity, further studies such as exome sequencing are required to identify a novel gene in order to confirm the locus heterogeneity in SWS.

Alterações comportamentais na Síndrome de Noonan: dados preliminares brasileiros / Behavioral disturbances in Noonan Syndrome: Brazilian preliminary data

Diferente de outros países de Europa e América do Norte, no Brasil, estudos sobre o perfil comportamental de pacientes com síndrome de Noonan (SN) são inexistentes. O objetivo do estudo foi traçar o perfil de funcionamento comportamental de 10 participantes (quatro do sexo feminino e seis do sexo masculino, sendo 8 adultos e 2 crianças), com mutação do gene PTPN11, compatível com a SN. Para isso, foram utilizados o Inventário de Comportamentos de Crianças e Adolescentes de 6 a 18 anos (CBCL/ 6-18) e o Inventário de Auto-Avaliação para Adultos de 18 a 59 anos (ASR). Os principais resultados apontam que na Escala de Funcionamento Adaptativo todos os participantes encontram-se na faixa de normalidade. Na Escala das Síndromes, os participantes adultos situam-se na normalidade e as crianças apresentam problemas, na faixa clínica, referentes às sub-escalas ansiedade/depressão, queixas somáticas e comportamento agressivo. Na Escala orientada pelo DSM, 25% dos pacientes adultos encontram-se na faixa limítrofe e clínica, respectivamente, quanto a problemas típicos de personalidade evitativa e problemas de personalidade anti-social e, ambas as crianças apresentaram escores dentro da faixa clínica nas sub-escalas problemas afetivos e problemas de ansiedade. Esta amostra que é relativamente homogênea em função do mesmo tipo de gene envolvido (PTPN11) mostrou um perfil comportamental médio, no caso dos adultos, dentro da normalidade. Entretanto, os perfis individuais, tanto dos participantes adultos como das crianças mostram diversos problemas de comportamento internalizantes e externalizantes.

Different from other countries of Europe and North American, studies about the behavioral profile of Noonan syndrome's patients are inexistent. The objective of this study was to report the profiles of behavioral functions of 10 participants (4 females and 6 males), with mutations in the PTPN11 gene. For this assessment it was used the Inventory of Behaviors of Children and Adolescents from 6 to 18 years (CBCL/6-18) and the Inventory of Auto-Evaluation for Adults from 18 to 59 years (ASR). The main results point that in Adaptive Functioning Scale all the participants were in the normality range. In the Syndrome Scale the adult participants were in normality range and the children were in clinical range to the sub-scales anxious/depressed, somatic complaints and aggressive behavior. In the DSM-Oriented Scale, 25% of the adult patients were in the borderline clinical range and clinical range, respectively, for Avoidant Personality Problems and Antisocial Personality Problems. About the both children in this scale were in the clinical range of Affective Problems and Anxiety Problems. This relatively homogenous sample, regarding the PTPN11 gene, shows a normal adult behavioral profile, on the average. However, the individual children and adult profiles show diverse internalizing and externalizing behavioral disturbances.