Prenatal and early diagnosis of Chinese 3-M syndrome patients with novel pathogenic variants

AbstractEpisodic encephalopathy due to mutations in the thiamine pyrophosphokinase 1 (TPK1) gene is a rare autosomal recessive metabolic disorder. Patients reported so far have onset in early childhood of acute encephalopathic episodes, which result in a progressive neurologic dysfunction including ataxia, dystonia, and spasticity. Here, we report the case of an infant with TPK1 deficiency (compound heterozygosity for two previously described pathogenic variants) presenting with two encephalopathic episodes and clinical stabilization under oral thiamine and biotin supplementation. In contrast to other reported cases, our patient showed an almost normal psychomotor development, which might be due to an early diagnosis and subsequent therapy.

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Somatic and germline analysis of a familial Rothmund–Thomson syndrome in two siblings with osteosarcoma

npj Genomic Medicine ◽

10.1038/s41525-020-00160-x ◽

2020 ◽

Vol 5 (1) ◽

Author(s):

Miriam Gutiérrez-Jimeno ◽

Elena Panizo-Morgado ◽

Ibon Tamayo ◽

Mikel San Julián ◽

Ana Catalán-Lambán ◽

...

Keyword(s):

Early Diagnosis ◽

Bone Tumors ◽

Gastrointestinal Disease ◽

Genomic Analysis ◽

Pathogenic Variants ◽

The Family ◽

Associated Symptoms ◽

Rothmund Thomson Syndrome ◽

Sparse Hair ◽

Bone Abnormalities

AbstractRothmund–Thomson syndrome (RTS) is characterized by a rash that begins in the first few months of life and eventually develops into poikiloderma. Associated symptoms are alterations in the teeth, sparse hair, thin eyebrows, lack of eyelashes, low stature, bone abnormalities, hematological illnesses, gastrointestinal disease, malnutrition, cataracts, and predisposition to cancer, principally to bone tumors and skin cancer. Diagnostic certitude is provided by a genetic study involving detection of pathogenic variants of the RECQL4 gene. We hereby present a familiar case of RTS in two siblings from a Portuguese family, both diagnosed with osteosarcoma. Genomic analysis (203 genes) of both tumors as well as germline analysis of the RECQL4 gene, thus confirming the syndrome in the family, have been performed. The relevance of clinical recognition of the hallmarks of the disease and thus early diagnosis with early intervention is highlighted.

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Persistent hyperinsulinaemic hypoglycaemia in children with Rubinstein–Taybi syndrome

Acta Endocrinologica ◽

10.1530/eje-19-0119 ◽

2019 ◽

Vol 181 (2) ◽

pp. 121-128 ◽

Cited By ~ 3

Author(s):

Alena Welters ◽

Ranna El-Khairi ◽

Antonia Dastamani ◽

Nadine Bachmann ◽

Carsten Bergmann ◽

...

Keyword(s):

Differential Diagnosis ◽

Next Generation Sequencing ◽

Early Diagnosis ◽

Metabolic Profile ◽

Clinical Characteristics ◽

Choanal Atresia ◽

Hyperinsulinaemic Hypoglycaemia ◽

Pathogenic Variants ◽

Gene Panels ◽

Generation Sequencing

Objective Genetic aetiology remains unknown in up to 50% of patients with persistent hyperinsulinaemic hypoglycaemia (HH). Several syndromes are associated with HH. We report Rubinstein–Taybi syndrome (RSTS) as one of the possible causes of persistent HH. Early diagnosis and treatment of HH is crucial to prevent hypoglycaemic brain injury. Design Four RSTS patients with HH were retrospectively analysed. Methods Genetic investigations included next-generation sequencing-based gene panels and exome sequencing. Clinical characteristics, metabolic profile during hypoglycaemia and treatment were reviewed. Results Disease-related EP300 or CREBBP variants were found in all patients, no pathogenic variants were found in a panel of genes associated with non-syndromic HH. Two patients had classic manifestations of RSTS, three had choanal atresia or stenosis. Diagnosis of HH varied from 1 day to 18 months of age. One patient was unresponsive to treatment with diazoxide, octreotide and nifedipine, but responded to sirolimus. All required gastrostomy feeding. Conclusions Given the rarity of RSTS (1:125 000) and HH (1:50 000), our observations indicate an association between these two conditions. We therefore recommend that clinicians should be vigilant in screening for HH in symptomatic infants with RSTS. In children with an apparent syndromic form of HH, RSTS should be considered in the differential diagnosis.

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Frequency of pathogenic variants in BRCA1 and BRCA2 genes in a population-based sample and in patients with breast or ovarian cancer

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.06.26-28 ◽

2020 ◽

pp. 26-28

Author(s):

А.С. Лимонова ◽

А.Н. Мешков ◽

А.И. Ершова ◽

А.В. Киселева ◽

О.П. Скирко ◽

...

Keyword(s):

Ovarian Cancer ◽

Early Diagnosis ◽

Population Based ◽

Targeted Prevention ◽

Cancer Genetic ◽

Brca1 And Brca2 ◽

Pathogenic Variants ◽

Brca1 And Brca2 Genes ◽

Oncological Diseases ◽

Custom Panel

Развитие молекулярно-генетических исследований позволило определить мутации в генах BRCA1 и BRCA2, приводящие к возникновению наследственных форм рака молочной железы (РМЖ) и рака яичников (РЯ). Проведение генетического тестирования открывает возможности осуществления ранней диагностики и направленной профилактики. Цель: сравнить распространенность патогенных вариантов в гене BRCA1 и BRCA2 у больных с верифицированным РМЖ/РЯ и в популяционной выборке женщин без онкологических заболеваний. Было включено 156 больных с диагнозом РМЖ/РЯ и 359 женщин без онкологических заболеваний из популяционной выборки ЭССЕ-Вологда. Для генетического анализа использована диагностическая панель, разработанная в ФГБУ «НМИЦ ТПМ», позволяющая выявлять варианты генов BRCA1 и BRCA2. Среди обследованных больных выявлено 5 носителей (3,21%) мутаций в гене BRCA1 (у 4 человек - rs80357906, 2,56%; у 1 человека - rs80357711, 0,64%) и 1 носитель (0,64%) rs80359550 в гене BRCA2. В выборке женщин без онкологических заболеваний носителей не выявлено. При наличии вариантов BRCA1 (rs80357906, rs80357711) или BRCA2 (rs80359550) риск развития РМЖ/РЯ повышен как минимум в 2,63 раза (р=0,0009). Выявление патогенных вариантов генов BRCA1 и BRCA2 может способствовать ранней диагностике и своевременной профилактике РМЖ и РЯ. Progress in genetics and molecular research enabled discovery of mutations in BRCA1 and BRCA2, leading to the development of hereditary breast (BC) and ovarian (OC) cancer. Genetic testing contributes to early diagnosis and targeted prevention of these cancers. Objective: To investigate the prevalence of pathogenic variants in BRCA1 and BRCA2 genes in patients with BC/OC and in a population-based sample without oncological diseases. Methods: 156 patients with diagnosed BC/OC were included in the study consecutively. In addition to it, 359 women from a population-based sample ESSE-Vologda were recruited in the study. Variants of BRCA1 and BRCA2 were detected using a custom panel. Results: Among cancer patients there were 5 carriers (3.21%) of mutations in BRCA1 (4 - rs80357906, 2.56%; 1 - rs80357711, 0.64%) and 1 carrier (0.64%) of rs80359550 in BRCA2. In a population-based sample no mutations were identified. The presence of BRCA1 (rs80357906, rs80357711) or BRCA2 (rs80359550) variants increases the risk of BC/OC at least 2.63 times (р=0.0009). Conclusion: Detection of pathogenic variants in BRCA1 and BRCA2 could facilitate early diagnosis and timely prevention of BC and OC.

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Red Flags: Barriers to Listening and Spoken Language in Children with Hearing Loss

Perspectives on Hearing and Hearing Disorders in Childhood ◽

10.1044/hhdc24.1.11 ◽

2014 ◽

Vol 24 (1) ◽

pp. 11-18

Author(s):

Andrea Bell ◽

K. Todd Houston

Keyword(s):

Hearing Loss ◽

Early Diagnosis ◽

Skill Acquisition ◽

Dynamic Process ◽

Spoken Language ◽

Red Flags ◽

Careful Monitoring ◽

Auditory Development ◽

Children With Hearing Loss ◽

Family Centered

To ensure optimal auditory development for the acquisition of spoken language, children with hearing loss require early diagnosis, effective ongoing audiological management, well fit and maintained hearing technology, and appropriate family-centered early intervention. When these elements are in place, children with hearing loss can achieve developmental and communicative outcomes that are comparable to their hearing peers. However, for these outcomes to occur, clinicians—early interventionists, speech-language pathologists, and pediatric audiologists—must participate in a dynamic process that requires careful monitoring of countless variables that could impact the child's skill acquisition. This paper addresses some of these variables or “red flags,” which often are indicators of both minor and major issues that clinicians may encounter when delivering services to young children with hearing loss and their families.

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