A Propósito do Artigo “Adults with Down Syndrome: Characterization of a Portuguese Sample”

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Etiologic Evaluation and Investigation of Global Development Delay and Intellectual Disability

Developmental Delay (DD) and Intellectual Disability (ID), depending on the affected individual being under or above five years-old, result from environmental or genetic causes during the developmental period, that manifest as a subnormal functioning of intellectual abilities. In western countries there is a prevalence of about 3%, with a great impact in the individuals, their families, as well as in the society. Etiologic diagnosis remains unknown in about 65-80% of the cases. It is a clinically heterogeneous condition as it can be sporadic or familiar, encompassing an autosomal dominant, recessive or X-linked transmission. Etiologic investigation emphasizes the importance of the clinical and family history as well as the physical examination, with special care for dysmorphologic evaluation. The authors reviewed DD/ ID focusing not only on clinical diagnosis but mostly on genetic causes and etiologic investigation. The protocol presented is followed by the Medical Genetics Department of Coimbra’s Paediatrics Hospital, in accordance to the international consensus

Reduced elastogenesis: a clue to the arteriosclerosis and emphysematous changes in Schimke immuno-osseous dysplasia?

BACKGROUND: Arteriosclerosis and emphysema develop in individuals with Schimke immuno-osseous dysplasia (SIOD), a multisystem disorder caused by biallelic mutations in SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a-like 1). However, the mechanism by which the vascular and pulmonary disease arises in SIOD remains unknown. METHODS: We reviewed the records of 65 patients with SMARCAL1 mutations. Molecular and immunohistochemical analyses were conducted on autopsy tissue from 4 SIOD patients. RESULTS: Thirty-two of 63 patients had signs of arteriosclerosis and 3 of 51 had signs of emphysema. The arteriosclerosis was characterized by intimal and medial hyperplasia, smooth muscle cell hyperplasia and fragmented and disorganized elastin fibers, and the pulmonary disease was characterized by panlobular enlargement of air spaces. Consistent with a cell autonomous disorder, SMARCAL1 was expressed in arterial and lung tissue, and both the aorta and lung of SIOD patients had reduced expression of elastin and alterations in the expression of regulators of elastin gene expression. CONCLUSIONS: This first comprehensive study of the vascular and pulmonary complications of SIOD shows that these commonly cause morbidity and mortality and might arise from impaired elastogenesis. Additionally, the effect of SMARCAL1 deficiency on elastin expression provides a model for understanding other features of SIOD

Juvenile polyposis of infancy in a child with deletion of BMPR1A and PTEN genes: Surgical approach

Juvenile polyposis of infancy is the most severe and life-threatening form of juvenile polyposis. This disease typically presents in the first two years of life with gastrointestinal bleeding, diarrhea, inanition, and exudative enteropathy. In very few reports concerning this entity, a large deletion in the long arm of chromosome 10 (10q23), encompassing the PTEN and BMPR1A genes, was found. The authors report a case of delayed diagnosis of juvenile polyposis of infancy at 6years of age. A 3.34Mb long de novo deletion was identified at 10q23.1q23.31, encompassing the PTEN and BMPR1A genes. The disease course was severe with diarrhea, abdominal pain, inanition, refractory anemia, rectal bleeding, hypoalbuminemia, and exudative enteropathy. A sub-total colectomy, combined with intraoperative endoscopic removal of ileal and rectal stump polyps, was required for palliative disease control

Intellectual disability, unusual facial morphology and hand anomalies in sibs

Here we report on a Portuguese family with three sisters who shared moderate intellectual disability, unusual facial morphology (short palpebral fissures; broad nasal tip; thin upper and lower vermillion; broad and pointed chin) and hand anomalies in two of them (short left third and fifth right metacarpals in one case; marked syndactyly between the third and fourth fingers in another). One of the sisters had microcephaly and short stature, and the other two were obese. Obesity and somewhat similar facial features were also present in the otherwise healthy mother. Despite the overlap with several known syndromes (Albright osteodystrophy; Filippi syndrome; Rubinstein-Taybi syndrome; microdeletion 2q37), we suggest this condition is previously unreported, and most likely displays an autosomal recessive pattern of inheritance

Intellectual disability, coarse face, relative macrocephaly, and cerebellar hypotrophy in two sisters

We report on two Portuguese sisters with a very similar phenotype characterized by severe intellectual disability, absent speech, relative macrocephaly, coarse face, cerebellar hypotrophy, and severe ataxia. Additional common features include increased thickness of the cranial vault, delayed dental eruption, talipes equino-varus, clinodactyly, and camptodactyly of the fifth finger. The older sister has retinal dystrophy and the younger sister has short stature. Their parents are consanguineous. We suggest this condition constitutes a previously unreported autosomal recessive entity

Descrição de uma forma autossômica dominante de síndrome de Kabuki por mutação no gene MLL2

Aims: Although there are more than 400 cases of Kabuki syndrome described in the literature, it is believed that this syndrome is under-diagnosed. Most cases occur sporadically, despite cases with autosomal dominant familial transmission being described. Here we describe three cases identified in the same family. Cases description: A family (mother and two children) was diagnosed with Kabuki syndrome. The three patients show the typical characteristics (facial appearance, musculoskeletal abnormalities, cognitive impairment, growth retardation and peculiar dermatoglyphic pattern) associated with other anomalies described in the syndrome (congenital heart disease and increased susceptibility to infections). Genetic studies revealed a nonsense mutation c.14710 C > T (p.Arg4904X) in the MLL2 gene in the three members of the family. Conclusions: With the description of another case of familial Kabuki syndrome, the authors wish to illustrate the autosomal dominant inheritance with variable expressivity, which are present in this situation, and to alert to the need for a rigorous clinical and molecular evaluation of the affected patient’s relatives, allowing appropriate genetic counseling

Cardiospondylocarpofacial syndrome as a distinct hereditary connective tissue disorder: novel missense variant in MAP3K7 in two unrelated patients

CDKL5 deficiency disorder is a rare X-linked condition that results in early onset of impairedmotor and cognitive skills such as motor rigidity, stereotypical hand movements and deficient language acquisition aswell as recurrent seizures. It is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene, which encodes a serine/threonine kinase involved in important neuronal processes such as cell signaling and neuron morphogenesis.FCT: UID/Multi/04326/2019 (CCMAR)info:eu-repo/semantics/publishedVersio

Velocity vector imaging to quantify left atrial function

The aim of our study was to assess the feasibility of a new image analysis, velocity vector imaging (VVI), in the assessment of left atrial volumes (LAV) and left atrial ejection fraction (LAEF). We retrospectively analysed 100 transthoracic echocardiographic findings in 71 men, and 29 women (mean age 57 ± 19.8 years). Two subgroups of patients were defined: (1) with left ventricular (LV) EF > 50%, and (2) LV EF < 50%. For the VVI method of indexed LAV assessment we used the apical four-chamber view. From the displacement of LA endocardial pixels time–volume curves were extracted which provided automatically data regarding indexed maximum LAV (LAVImax), indexed minimum LAV (LAVImin), and LAEF. LAVs and LAEF by 2-dimensional echocardiograhy (2DE) were measured by Simpson’s biplane disc summation method. Comparing LAVImax, LAVImin, and LAEF by VVI versus 2DE in the total study population, we found significant correlations: r = 0.94, P < 0.0001, r = 0.94, P < 0.0001, r = 0.79, P < 0.0001, respectively. In addition, LAVImax ≥ 40 ml/m2 was 94% sensitive and 72% specific, LAVImin ≥ 27 ml/m2 was 90% sensitive and 86% specific, and LAEF < 30% was 80% sensitive and 96% specific for the detection of LV systolic dysfunction. There were highly significant inverse associations of LAVImax and LAVImin to LVEF. LAEF was also significantly related to LV systolic function. When comparing the time required for VVI and 2DE measurements, VVI led to 62% reduction in the measurement time. In conclusion, VVI is a feasible method for the assessment of LAVs and LAEF. It provides close agreement with that measured by conventional 2DE Simpson’s biplane method with significant time saved