Atypical Phenotype in Two Patients with LAMA2 Mutations

Congenital muscular dystrophy type 1A is caused by mutations in the LAMA2 gene, which encodes the a2-chain of laminin. We report two patients with partial laminin-a2 deficiency and atypical phenotypes, one with almost exclusive central nervous system involvement (cognitive impairment and refractory epilepsy) and the second with marked cardiac dysfunction, rigid spine syndrome and limb-girdle weakness. Patients underwent clinical, histopathological, imaging and genetic studies. Both cases have two heterozygous LAMA2 variants sharing a potentially pathogenic missense mutation c.2461A>C (p.Thr821Pro) located in exon 18. Brain MRI was instrumental for the diagnosis, since muscular examination and motor achievements were normal in the first patient and there was a severe cardiac involvement in the second. The clinical phenotype of the patients is markedly different which could in part be explained by the different combination of mutations types (two missense versus a missense and a truncating mutation).

Etiologia das Cardiopatias Congénitas. Ocorrência em Familiares

Num total de 2806 crianças de idade inferior a 13 anos portadoras de cardiopatia congénita isolada e observadas durante um período de 14 anos e 2 meses, averiguou-se a ocorrência de cardiopatias congénitas nos seus familiares, globalmente e pelos diversos graus de parentesco. Os resultados obtidos mostram maior ocorrência de cardiopatias congénitas nos familiares dos propositi (1,32%) que na população em geral (0,8%). A ocorrência foi de 1,28% nos familiares de 1º grau e de 1,38% nos restantes. Verificou-se a existência de cardiopatias congénitas concordantes entre os familiares de 1º grau. A taxa média global de concordância encontrada foi de 22,64%. Não houve correlação significativa entre as cardiopatias discordantes. Os resultados obtidos permitem que, na maioria dos casos, possa ser dada uma opinião favorável no que respeita ao aconselhamento genético.

Cardiopatias Congénitas e Síndromes

Procurou-se a probabilidade de cada tipo de cardiopatia congénita ocorrer como parte de síndromes malformativas. Estudaram-se em 14 anos 3027 crianças de idade inferior a 13 anos, com diagnóstico definitivo de cardiopatias congénitas bem definidas. A ocorrência de síndromes verificou-se em 208 casos (6,87%). Esta percentagem foi maior nas crianças com fenótipo feminino (8,22%) do que nas crianças com fenótipo masculino (5,51%). Enquadraram-se em síndromes, em percentagens muito superiores os defeitos do septo aurículo-ventricular (38,61%), a atrésia da pulmonar com (16,13%) e sem comunicação inter-ventricular (18,18%), as estenoses das artérias pulmonares (84,21%), a estenose aórtica supravalvular (69,23%) e as dextrocardias com cardiopatia (10%). Englobaram-se em síndromes, em percentagens inferiores a comunicação inter-ventricular, a estenose pulmonar valvular, a tetralogia de Fallot, a estenose aórtica, a comunicação inter-auricular e a coarctação da aorta. A transposição completa dos grandes vasos e outras cardiopatias congénitas mais raras não fizeram parte de síndromes.

Association of Intestinal Malrotation and Bochdalek Hernia in an Adult: a Case Report

Background Late presentations of congenital diaphragmatic hernia are rare and differ from the classic neonatal presentation. The association with other congenital malformations in children, mainly intestinal malrotation, is well documented. The diagnosis of this association in adults is very rare, and depends on a high degree of suspicion. Case presentation We report a case of a 50-year-old female Caucasian patient with a previous history of intestinal malrotation diagnosed in adolescence and treated conservatively. She was referred to the hospital with signs and symptoms of intestinal obstruction. The patient undertook computed tomography that confirmed small bowel obstruction with no obvious cause, and a right subphrenic abscess with right empyema was also present. An exploratory laparotomy was performed that revealed an intestinal malrotation associated with a right gangrenous and perforated Bochdalek hernia. Resection of the affected small bowel, closure of the Bochdalek foramen and the Ladd procedure were carried out. Conclusion This case shows a rare association of two rare conditions in adults, and highlights the challenge in reaching the diagnosis and management options.

Torpedo Maculopathy with an Anisometropic Amblyopia in a 5-Year-Old Caucasian Girl: Case Report

The aim of this study is to report a clinical case of asymptomatic female Caucasian children with torpedo maculopathy. A 5-year-old girl was referred to our clinic for routine evaluation. The ophthalmic examination revealed best-corrected visual acuity of 20/20 in both eyes, without any changes in the biomicroscopy. Fundus examination showed normal findings in one eye, whereas in the contralateral eye it disclosed, in the temporal sector of the macular region, a whitish, atrophic, oval chorioretinal lesion with clearly defined margins. Posterior evaluations documented the stability of the lesion. Torpedo maculopathy diagnosis is based on its characteristic shape and peculiar location. The differential diagnosis has to be established versus choroidal lesions (melanoma and nevus), congenital or iatrogenic hyperplasia of the retinal pigment epithelium (RPE) and particularly versus the congenital pigmented lesions associated with Gardner's syndrome.

Atrial Septal Defects

Atrial septal defects are the third most common type of congenital heart disease. Included in this group of malformations are several types of atrial communications that allow shunting of blood between the systemic and the pulmonary circulations. Most children with isolated atrial septal defects are free of symptoms, but the rates of exercise intolerance, atrial tachyarrhythmias, right ventricular dysfunction, and pulmonary hypertension increase with advancing age and life expectancy is reduced in adults with untreated defects. The risk of development of pulmonary vascular disease, a potentially lethal complication, is higher in female patients and in older adults with untreated defects. Surgical closure is safe and effective and when done before age 25 years is associated with normal life expectancy. Transcatheter closure offers a less invasive alternative for patients with a secundum defect who fulfil anatomical and size criteria. In this Seminar we review the causes, anatomy, pathophysiology, treatment, and outcomes of atrial septal defects in children and adult patients in whom this defect is the primary cardiac anomaly.

Diagnóstico Pré-Natal das Cardiopatias Congénitas. Realidade Actual no Sul do País

Com o objectivo de avaliar a realidade actual do diagnóstico pré-natal das cardiopatias congénitas realizou-se um estudo prospectivo da actividade do Sector de Cardiologia Fetal num período de 2 anos. Este estudo abrangeu uma população fetal constituída por um grupo de 948 fetos observados no Serviço, 348 no período de Janeiro a Junho de 1993 (Grupo 1) e 600 de Julho de 1993 a Dezembro de 1994 (Grupo II), assim como uma população de 185 recém-nascidos, 20 (Grupo 1) internados por cardiopatia grave durante o período de Janeiro a Junho de 1993 e 165 observados de Janeiro a Junho de 1994 (Grupo II). Registaram-se os dados relativos a gravidez e ecografia obstétrica, risco fetal para cardiopatia, idade no momento do diagnóstico e tipo de cardiopatia. As populações respectivas de cada um dos grupos foram comparadas entre si. Nos dois grupos da população fetal os principais motivos de referência para ecocardiograma foram os factores maternos (18%) e familiares (14%) sendo os factores fetais causas menos frequentes (7%), nomeadamente a suspeita obstétrica de cardiopatia (6%) e as arritmias fetais (7%). No entanto, a incidência de cardiopatia fetal no grupo 1 foi de 32% para a suspeita obstétrica de cardiopatia e de 13% para a arritmia fetal; no grupo II esta incidência foi respectivamente de 48% e de 36%. Nos dois grupos os factores maternos associaram-se a cardiopatia em 2° o dos casos; não houve associação com factores familiares. Apresentavam factor de risco 30% dos recém-nascidos do grupo 1. No grupo II este valor foi de 36% nos recém-nascidos internados e de 22% nos do ambulatório. O ecocardiograma fetal foi realizado em 3 recém-nascidos do grupo 1 e em 12 casos do grupo II sendo o diagnóstico pré-natal feito em 2 e 3 casos respectivamente. Conclui-se que, exceptuando o aumento do número de fetos referenciados e a melhoria na acuidade do diagnóstico obstétrico, no período de estudo não houve modificações significativas na identificação dos riscos, continuando a maioria dos recém-nascidos com cardiopatia a nascer sem diagnóstico pré-natal. Torna-se necessário continuar a política de divulgação desta área, em particular junto dos médicos que prestam cuidados primários de saúde.

Insuficiência Pulmonar Valvular Congénita

Descrevem-se 4 casos de Insuficiência Pulmonar Valvular Congénita com septo interventricular intacto em crianças de sexo masculino com idades compreendidas entre os 20 meses e os 10 anos, na 1a observação na Consulta de Cardiologia Pediátrica. 0 diagnóstico clínico de regurgitação pulmonar foi confirmado por electrocardiograma, fonocardiograma e radiografia de tórax em todos os doentes e também por ecocardiograma, exame hemodinâmico e angiocardiográfico em 3 deles. Após um follow-up que variou entre 1 e 9 anos, média 5 anos e 2 meses, concluiu-se que a Insuficiência Pulmonar Valvular Congénita, como cardiopatia isolada, é bem tolerada em idades pediátricas e compatível com desenvolvimento físico e actividade normais.

Non-Progressive Leukoencephalopathy with Bilateral Temporal Cysts

We report two cases of a peculiar leukoencephalopathy with temporal cysts. Both patients have a non-progressive neurological disorder with mental retardation, microcephaly and sensorineural deafness although clinical differences between them may reflect a different aetiology. The metabolic disorders with white matter involvement and the recently described leukoencephalopathies (Van Der Knaap disease, 'vanishing white matter disease') were excluded based on clinical, biologic and imaging findings. Cytomegalovirus infection is a likely possibility in the first case although the magnetic resonance imaging picture is only partially similar to previously reported cases. Our patients are strikingly similar to the patients reported by Deonna et al. and Olivier et al. We discuss the clinical and imaging findings in our patients and the differential diagnosis considering the known disorders of the white matter in childhood.

Acute Kidney Injury after Pediatric Cardiac Surgery: Risk Factors and Outcomes. Proposal for a Predictive Model

Objectives: To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. Methods: This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. Results: Of the 325 patients included, median age three years (1 day---18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients’ age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. Conclusions: AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients.

Pseudo-Kaposi's Sarcoma Because of Suction-Socket Lower Limb Prosthesis

Pseudo-Kaposi sarcoma is a benign reactive vascular proliferation mainly involving the lower legs, which can be related to acquired chronic venous insufficiency or congenital arteriovenous malformations. In its most common presentation, acroangiodermatitis is seen in patients with chronic venous insufficiency of the lower limbs as an exaggeration of the stasis dermatitis. However, rare reports of acroangiodermatitis include descriptions in amputees (especially in those with poorly fitting suction-type devices), in patients undergoing hemodialysis (with lesions developing distally to arteriovenous shunts) and in patients with paralyzed legs. We report on a 28 year-old-male who presented pseudo-Kaposi's sarcoma in an amputation stump because of suction-socket lower limb prosthesis.

Genetic Screening of LCA in Belgium: Predominance of CEP290 and Identification of Potential Modifier Alleles in AHI1 of CEP290-Related Phenotypes

Leber Congenital Amaurosis (LCA), the most severe inherited retinal dystrophy, is genetically heterogeneous, with 14 genes accounting for 70% of patients. Here, 91 LCA probands underwent LCA chip analysis and subsequent sequencing of 6 genes (CEP290, CRB1, RPE65, GUCY2D, AIPL1and CRX), revealing mutations in 69% of the cohort, with major involvement of CEP290 (30%). In addition, 11 patients with early-onset retinal dystrophy (EORD) and 13 patients with Senior-Loken syndrome (SLS), LCA-Joubert syndrome (LCA-JS) or cerebello-oculo-renal syndrome (CORS) were included. Exhaustive re-inspection of the overall phenotypes in our LCA cohort revealed novel insights mainly regarding the CEP290-related phenotype. The AHI1 gene was screened as a candidate modifier gene in three patients with the same CEP290 genotype but different neurological involvement. Interestingly, a heterozygous novel AHI1 mutation, p.Asn811Lys, was found in the most severely affected patient. Moreover, AHI1 screening in five other patients with CEP290-related disease and neurological involvement revealed a second novel missense variant, p.His758Pro, in one LCA patient with mild mental retardation and autism. These two AHI1 mutations might thus represent neurological modifiers of CEP290-related disease.

Urinary Tract Effects of HPSE2 Mutations

Urofacial syndrome (UFS) is an autosomal recessive congenital disease featuring grimacing and incomplete bladder emptying. Mutations of HPSE2, encoding heparanase 2, a heparanase 1 inhibitor, occur in UFS, but knowledge about the HPSE2 mutation spectrum is limited. Here, seven UFS kindreds with HPSE2 mutations are presented, including one with deleted asparagine 254, suggesting a role for this amino acid, which is conserved in vertebrate orthologs. HPSE2 mutations were absent in 23 non-neurogenic neurogenic bladder probands and, of 439 families with nonsyndromic vesicoureteric reflux, only one carried a putative pathogenic HPSE2 variant. Homozygous Hpse2 mutant mouse bladders contained urine more often than did wild-type organs, phenocopying human UFS. Pelvic ganglia neural cell bodies contained heparanase 1, heparanase 2, and leucine-rich repeats and immunoglobulin-like domains-2 (LRIG2), which is mutated in certain UFS families. In conclusion, heparanase 2 is an autonomic neural protein implicated in bladder emptying, but HPSE2 variants are uncommon in urinary diseases resembling UFS.