Multicentric Carpotarsal Osteolysis Syndrome in a Mother and Daughter with a MAFB Missense Variant and Natural History of the Disease.

Multicentric carpotarsal osteolysis syndrome (MCTO; MIM #166300) is a rare skeletal disorder characterized by osteolysis affecting particularly the carpal, metacarpal, and tarsal bones, although other bones might be involved. MCTO is an autosomal dominant disease caused by heterozygous variants in the MAFB gene, frequently misdiagnosed as juvenile rheumatoid arthritis due to similar clinical manifestations. This study reports the first Brazilian family diagnosed with MCTO with progressive osteolysis of the carpal and tarsal bones, presenting a c.161C>T (p.Ser54Leu) heterozygous variant in the MAFB gene, describing the clinical, radiological, and molecular findings, compared with literature data, and discussing the different clinical and molecular diagnosis, as well as the natural history of the disease. Since MCTO is a disorder with progressive symptoms, an early diagnosis is important to avoid unnecessary investigations and treatments and to provide the proper follow-up.

Gomez-López-Hernández syndrome: A case report with clinical and molecular evaluation and literature review.

Gomez-López-Hernández syndrome (GLHS) is characterized by rhombencephalosynapsis (RES), alopecia, trigeminal anesthesia and a distinctive phenotype, including brachyturricephaly. It has been suggested that GLHS should be considered as part of the spectrum of RES-associated conditions that include alopecia, trigeminal anesthesia, and craniofacial anomalies, rather than a distinct entity. To the best of our knowledge, 57 patients with GLHS have been described. Despite its first description in 1979, the etiology of this syndrome remains unknown. Here, we describe, to our knowledge, the first case of a patient with GLHS who was molecularly evaluated and had been prenatally exposed to misoprostol. We also reviewed the clinical and morphological features of the patients described to date to better delineate the phenotype and focus on any evidence for adverse pregnancy outcomes or exposure, including teratogens.

Radiografia simples de abdome no diagnóstico da impactação fecal em crianças com constipação intestinal: comparação entre três escores radiológicos / Abdominal radiograph in the assessment of fecal impaction in children with functional constipation: comparing three scoring systems

OBJETIVOS: Comparar três escores radiológicos na pesquisa de impactação fecal em crianças com constipação intestinal. Verificar, ainda, se estes escores radiológicos são úteis na avaliação da terapia de desimpactação fecal e se apresentam relação com o tempo de trânsito colônico total. MATERIAL E MÉTODOS: Os escores de Barr, Blethyn e Leech foram aferidos por três observadores, de forma independente, em 123 radiografias de abdome. A concordância interobservador no diagnóstico da impactação fecal foi calculada para os três escores. Em 30 radiografias, foi feita a análise dos escores antes e após a desimpactação fecal. O tempo de trânsito colônico total foi calculado em 59 radiografias com o emprego de marcadores radiopacos. RESULTADOS: A concordância entre os pares de observadores, avaliada pelo coeficiente de Kappa, foi boa para os escores de Barr (0,56, 0,59 e 0,69) e Leech (0,53, 0,58 e 0,61). O escore de Blethyn apresentou menores coeficientes de Kappa (0,26, 0,32 e 0,36). Na comparação dos métodos, Leech e Barr mostraram boa correlação. Após a desimpactação fecal, houve redução estatisticamente significante (p < 0,001) dos escores, mais expressiva com o escore de Barr. Não houve relação entre os escores radiológicos e o tempo de trânsito colônico. CONCLUSÕES: Não há relação entre impactação fecal avaliada pela radiografia de abdome e o tempo de trânsito colônico total. A radiografia simples pode ser um instrumento útil ao diagnóstico da impactação fecal. O escore de Barr pode ser considerado um bom método de análise, sobretudo para avaliação da resposta ao tratamento da impactação fecal.

OBJECTIVES: To compare three radiological scores in the study of fecal impaction in children with constipation. To investigate whether these radiological scores are useful in the assessment of fecal disimpaction therapy and if they present a relation with total colonic transit time. METHODS: The Barr, Blethyn and Leech scores were measured by three observers, independently, in 123 abdominal radiographs. Interobserver agreement in the diagnosis of fecal impaction was calculated for the three scores. In 30 radiographs, the analysis of the scores was performed before and after fecal disimpaction. Total colonic transit time was calculated in 59 radiographs with the use of radiopaque markers. RESULTS: The agreement between pairs of observers was assessed by the kappa coefficient and was good for the Barr (0.56, 0.59 and 0.69) and Leech scores (0.53, 0.58 and 0.61). The Blethyn score presented lower kappa coefficients (0.26, 0.32 and 0.36). In the comparison of methods, Leech and Barr showed a good correlation. After fecal disimpaction, there was a statistically significant reduction (p < 0.001) of scores, most significantly with the Barr score. There was no relation between radiographic scores and colonic transit time. CONCLUSIONS: There is no relation between fecal impaction assessed by radiography of the abdomen and total colonic transit time. Plain radiographs may be a useful tool for the diagnosis of fecal impaction. The Barr score can be considered a good method of analysis, especially to assess the response to treatment of fecal impaction.

Cytogenomic characterization of an unexpected 17.6 Mb 9p deletion associated to a 14.8 Mb 20p duplication in a dysmorphic patient with multiple congenital anomalies presenting a normal G-banding karyotype.

We describe a female patient with developmental delay, dysmorphic features and multiple congenital anomalies who presented a normal G-banded karyotype at the 550-band resolution. Array and multiplex-ligation probe amplification (MLPA) techniques identified an unexpected large unbalanced genomic aberration: a 17.6Mb deletion of 9p associated to a 14.8 Mb duplication of 20p. The deleted 9p genes, especially CER1 and FREM1, seem to be more relevant to the phenotype than the duplicated 20p genes. This study also shows the relevance of using molecular techniques to make an accurate diagnosis in patients with dysmorphic features and multiple anomalies suggestive of chromosome aberration, even if on G-banding their karyotype appears to be normal. Fluorescence in situ hybridization (FISH) was necessary to identify a masked balanced translocation in the patient's mother, indicating the importance of associating cytogenetic and molecular techniques in clinical genetics, given the implications for patient management and genetic counseling.