Congenital intrahepatic arterioportal fistula presenting as severe undernutrition and chronic watery diarrhea in a 2-year-old girl

Intrahepatic arterioportal fistula (IAPF) is a rare cause of portal hypertension in young children. We report the case of a 2-year-old girl with severe undernutrition, chronic watery diarrhea, and gastrointestinal bleeding because of a congenital intrahepatic arterioportal fistula. Radiographic embolization and surgical ligation of the left hepatic artery were attempted, with no resolution of the symptoms. So, a left lobectomy was performed, with excellent results and prompt disappearance of the diarrhea. Hepatectomy should be considered as a definitive and reliable. therapy for congenital IAPF. (C) 2009 Elsevier Inc. All rights reserved.

De novo copy number variants identify new genes and loci in isolated sporadic tetralogy of Fallot

Tetralogy of Fallot (TOF), the most common severe congenital heart malformation, occurs sporadically, without other anomaly, and from unknown cause in 70% of cases. Through a genome-wide survey of 114 subjects with TOF and their unaffected parents, we identified 11 de novo copy number variants (CNVs) that were absent or extremely rare (<0.1%) in 2,265 controls. We then examined a second, independent TOF cohort (n = 398) for additional CNVs at these loci. We identified CNVs at chromosome 1q21.1 in 1% (5/512, P = 0.0002, OR = 22.3) of nonsyndromic sporadic TOF cases. We also identified recurrent CNVs at 3p25.1, 7p21.3 and 22q11.2. CNVs in a single subject with TOF occurred at six loci, two that encode known (NOTCH1, JAG1) disease-associated genes. Our findings predict that at least 10% (4.5-15.5%, 95% confidence interval) of sporadic nonsyndromic TOF cases result from de novo CNVs and suggest that mutations within these loci might be etiologic in other cases of TOF.

Communicative and psycholinguistic abilities in children with phenylketonuria and congenital hypothyroidism

The Neonatal Screening for Inborn Errors of Metabolism of the Association of Parents and Friends of Special Needs Individuals (APAE) - Bauru, Brazil, was implanted and accredited by the Brazilian Ministry of Health in 1998. It covers about 286 cities of the Bauru region and 420 collection spots. Their activities include screening, diagnosis, treatment and assistance to congenital hypothyroidism (CH) and phenylketonuria (PKU), among others. In 2005, a partnership was established with the Department of Speech-Language Pathology and Audiology, Bauru School of Dentistry, University of São Paulo, Bauru, seeking to characterize and to follow, by means of research studies, the development of the communicative abilities of children with CH and PKU. OBJECTIVE: The aim of this study was to describe communicative and psycholinguistic abilities in children with CH and PKU. MATERIALS AND METHODS: Sixty-eight children (25 children aged 1 to 120 months with PKU and 43 children aged 1 to 60 months with CH) participated in the study. The handbooks were analyzed and different instruments were applied (Observation of Communication Behavior, Early Language Milestone Scale, Peabody Picture Vocabulary Test, Gesell & Amatruda's Behavioral Development Scale, Portage Operation Inventory, Language Development Evaluation Scale, Denver Developmental Screening Test, ABFW Child Language Test-phonology and Illinois Test of Psycholinguistic Abilities), according to the children's age group and developmental level. RESULTS: It was observed that the children with PKU and CH at risk for alterations in their developmental abilities (motor, cognitive, linguistic, adaptive and personal-social), mainly in the first years of life. Alterations in the psycholinguistic abilities were also found, mainly after the preschool age. Attention deficits, language and cognitive alterations were more often observed in children with CH, while attention deficits with hyperactivity and alterations in the personal-social, language and motor adaptive abilities were more frequent in children with PKU. CONCLUSION: CH and PKU can cause communicative and psycholinguistic alterations that compromise the communication and affect the social integration and learning of these individuals, proving the need of having these abilities assisted by a speech and language pathologist.

Congenital eruption cyst: a case report

Congenital pathologies are those existing at or dating from birth. Occurrence of congenital cystic lesions in the oral cavity is uncommon in neonates. Eruption cyst (EC) is listed among these unusual lesions. It occurs within the mucosa overlying teeth that are about to erupt and, according to the current World Health Organization (WHO) classification of epithelial cysts of the jaws, EC is a separate entity. This paper presents a case of congenital EC successfully managed by close monitoring of the lesion, without any surgical procedure or tooth extraction. Eruption of the teeth involved, primary central incisors, occurred at the fourth month of age. During this time neither the child nor mother had any complication such as pain on sucking, refusal to feed, airway obstruction, or aspiration of fluids or teeth.

Oral findings and dental care in a patient with myelomeningocele: case report of a 3-year-old child

Myelomeningocele (MMC) is a congenital malformation of the neural tube that occurs in the first weeks of pregnancy. This malformation refers to the caudal non-closure of the neural tube and neural tissue exposure, which lead to neurological problems, such as hydrocephalus, motor disability, genitourinary tract and skeletal abnormalities and mental retardation. Patients with MMC have an acknowledged predisposition to latex allergy and are usually at a high caries risk and activity due to poor oral hygiene, fermentable carbon hydrate-rich diet and prolonged use of sugar-containing medications. This paper addresses the common oral findings in pediatric patients with MMC, discusses the strategies and precautions to deal with these individuals and reports the dental care to a young child diagnosed with this condition.

Etiology of congenital hypothyroidism using thyroglobulin and ultrasound combination

Methods currently employed to establish the etiology of congenital hypothyroidism include thyroid ultrasound and scintigraphic exams. Thyroglobulin is a protein almost exclusively secreted by thyroid tissue and indirectly reflects the amount of follicular cells. Even though thyroglobulin is easy to measure, it has been not frequently used because of discordant results to distinguish mainly athyreosis and ectopy (dysgenesis). Knowing the differences in inheritance and prognosis of thyroid dysgenesis and dyshormonogenesis, it is important to define the etiology of CH, combining tools that are easy, fast and available in most medical centers. Our objective was to evaluate and compare color Doppler ultrasound and serum thyroglobulin with radionuclide scan to define the etiology of congenital hypothyroidism. We evaluated 38 children above 3 years-old off-treatment that performed serum thyroglobulin by immunofluorometric assay, color Doppler ultrasound and radionuclide study. On color Doppler ultrasound, 11 patients had athyreosis, 5 ectopic glands, being I associated to hemiagenesis. Twenty one had topic thyroid (3 goiters, 10 normal, 8 hypoplastic). Hemiagenesis and cystic lesion were not revealed by radionuclide scan. We observed substantial agreement between color Doppler ultrasound and radionuclide scan (kappa=0.745, p<0.0001). Serum thyroglobulin in athyreosis ranged from <1.0 to 18.7 mu g/L. Patients with ectopic glands showed wider thyroglobulin range (4.5 to 123 mu g/L, median 28.4 mu g/L). Only one patient showed thyroglobulin deficiency. By using color Doppler ultrasound and serum thyroglobulin levels as valuable combined tools, we established the etiology of congenital hypothyroidism limiting excessive and harmful exams in children, like radionuclide scan.

Phenotypic variation among four family members with congenital hypothyroidism caused by two distinct thyroglobulin gene mutations

Background: Thyroglobulin (Tg) is a large glycoprotein that is intimately involved in the biosynthesis of thyroxine and triiodothyronine. At least 38 mutations have been described in the Tg gene that are associated with varying degrees of hypothyroidism. We studied the Tg gene in four related subjects with congenital hypothyroidism. Summary: We found a novel compound heterozygous constellation (IVS30 + 1G>T/A2215D) in a brother and sister and one previously described related mutation (IVS30+1G>T) in their two sibling second degree cousins. The brother with the IVS30 + 1G>T/A2215D mutation and the two siblings with the IVS30+1G>T mutation had fetal or neonatal goiter and all had hypothyroidism. Conclusions: This study further confirms the association of the IVS30+1G>T mutation of the Tg gene with hypothyroidism. Computer analysis predicts that the A2215D mutation, first reported here, should cause structural instability of Tg but when present as a compound heterozygous mutation with IVS30+G>T/A its effect is unclear but is likely to be influenced by iodine intake.

Clinical indicators of ineffective airway clearance in children with congenital heart disease

To analyse the sensitivity and specificity of clinical indicators of ineffective airway clearance in children with congenital heart disease and to identify the indicators that have high predictive power. The precise establishment of nursing diagnoses has been found to be one of the factors contributing to higher quality of care and cost reduction in healthcare institutions. The use of indicators to diagnose ineffective airway clearance could improve care of children with congenital heart disease. Longitudinal study. Participants consisted of 45 children, <= 1 year of age, with congenital heart disease, who had not had definitive or palliative surgical correction. Six assessments were made at 2-day intervals. Each clinical indicator was defined based on previously established operational criteria. Sensitivity, specificity and positive and negative predictive values of each indicator were calculated based on a model for the longitudinal data. A nursing diagnosis of ineffective airway clearance was made in 31% of patients on the first assessment, rising to 71% on the last assessment, for a 40% increase. Sensitivity was highest for Changes in Respiratory Rates/Rhythms (0.99), followed by Adventitious Breath Sounds (0.97), Sputum Production (0.85) and Restlessness (0.53). Specificity was higher for Sputum Production (0.92), followed by Restlessness (0.73), Adventitious Breath Sounds (0.70) and Changes in Respiratory Rates/Rhythms (0.17). The best positive predictive values occurred for Sputum Production (0.93) and Adventitious Breath Sounds (0.80). Adventitious Breath Sounds followed by Sputum Production were the indicators that had the best overall sensitivity and specificity as well as the highest positive predictive values. The use of simple indicators in nursing diagnoses can improve identification of ineffective airway clearance in children with congenital heart disease, thus leading to early treatment of the problem and better care for these children.

Molecular analysis of CYP21A2 can optimize the follow-up of positive results in newborn screening for congenital adrenal hyperplasia

Neonatal screening for congenital adrenal hyperplasia (CAH) is useful in diagnosing salt wasting form (SW). However, there are difficulties in interpreting positive results in asymptomatic newborns. The main objective is to analyze genotyping as a confirmatory test in children with neonatal positive results. Patients comprised 23 CAH children and 19 asymptomatic infants with persistently elevated 17-hydroxyprogesterone (17OHP) levels. CYP21A2 gene was sequenced and genotypes were grouped according to the enzymatic activity of the less severe allele: A1 null, A2 < 2%, B 3-7%, C > 20%. Twenty-one children with neonatal symptoms and/or 17OHP levels > 80 ng/ml carried A genotypes, except two virilized girls (17OHP < 50 ng/ml) without CAH genotypes. Patients carrying SW genotypes (A1, A2) and low serum sodium levels presented with neonatal 17OHP > 200 ng/ml. Three asymptomatic boys carried simple virilizing genotypes (A2 and B): in two, the symptoms began at 18 months; another two asymptomatic boys had nonclassical genotypes (C). The remaining 14 patients did not present CAH genotypes, and their 17OHP levels were normalized by 14 months of age. Molecular analysis is useful as a confirmatory test of CAH, mainly in boys. It can predict clinical course, identify false-positives and help distinguish between clinical forms of CAH.

Age and Method-dependent Variability of Predicted Oxygen Consumption in Congenital Heart Disease

Background and Purpose. There has been a lot of debate about the use of predicted oxygen consumption to calculate pulmonary vascular resistance using the Fick principle. We therefore comparatively analyzed predicted oxygen consumption in infants and children in specific age groups, using different methods (formulas), as an attempt to better understand the usefulness and limitations of predictions. Methods and Results. Four models (LaFarge & Miettinen, Bergstra et al., Lindahl, and Lundell et al.) were used to predict oxygen consumption in 200 acyanotic patients with congenital cardiac defects aged 0-2.0, > 2.0-4.0, > 4.0-6.0, and > 6.0-8.75 years (median 2.04 years). Significant differences were observed between the age groups (P < .001) and between the methods (P < .001), not related to diagnoses. Differences between methods were more impressive in the first age group (P < .01). In patients aged 0-2.0 years, the lowest values of oxygen consumption (corresponding to the highest estimates of pulmonary vascular resistance) were obtained with the method of Lindahl; above this age, any method except that of Lundell et al. Conclusions. Although measuring oxygen consumption is always preferable, a rational use of predictions, using different methods, may be of help in situations where measurements are definitely not possible.

The actual incidence of congenital adrenal hyperplasia in Brazil may not be as high as inferred - An estimate based on a public neonatal screening program in the state of Goias

The incidence of 21-hydroxylase deficiency (CYP21 D) congenital adrenal hyperplasia (CAH) in Brazil is purportedly one of the highest in the world (1:7,533). However, this information is not based on official data. The aim of this study was to determine the incidence of CYP21 D CAH in the state of Goias, Brazil, based on the 2005 results of government-funded mandatory screening. Of the live births during this period, 92.95% were screened by heel-prick capillary 17 alpha-hydroxyprogesterone (17-OHP). Of these, 82,343 were normal, 28 were at high risk for CAH and 232 at low risk for CAH. Eight cases, all from the high risk group, were confirmed. Eight asymptomatic children at 6-18 months of age still have high 17-OHP levels and await diagnostic definition. Based on the number of confirmed CYP21 D CAH cases among the 82,603 screened, the estimated annual incidence of the disease was 1:10,325, lower than the previously reported rate in Brazil.

The surgical repair of half-nose

Absence of half-nose is an extremely rare congenital malformation, which has a devastating impact on the patient and the family. A review of indexed English-language literature found 91 cases of half-nose, including 50 patients with proboscis lateralis. Pathogenesis is not clear, and the reported cases have sporadically occurred. Many aspects must be considered when reconstructing a congenital half-nose, such as timing of surgery, type of tissue to be used and the need to reconstruct nasal airway. The aim of this article is to present personal experience in seven cases of half-nose reconstruction, in order to review the literature regarding to this rare entity, highlighting aspects of incidence, pathogenesis and surgical treatment. Nasal reconstruction was performed at ages of 5-7 years to minimise psychological trauma. Forehead skin demonstrated to be an excellent donor site to re-surface the nose. For the inner lining, contralateral cutaneous nasal flap was our preference. Concerning the nasal framework reconstruction, alar contour was restored using a cartilage graft from the lower portion of ear tragus and concha. (C) 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

The Tessier Number 5 Facial Cleft: Surgical Strategies and Outcomes in Six Patients

The Tessier no. 5 facial cleft is an extremely rare congenital malformation. Only 26 cases have been described In the English-language literature. The cleft begins In the upper lip just medial to the oral commissure, extending across the cheek as a groove ending at the junction of the middle and lateral thirds of the lower eyelid. The bone Involvement usually Includes an alveolar cleft in the premolar region, extends across the maxilla lateral to the Infraorbital nerve, up to the infraorbital rim and orbital floor. The goals of the surgical procedure Include reconstructing the lower eyelid, repositioning the lateral canthus, closure of the labiomaxillary cleft, and restoration of the skeletal continuity (including the orbital floor defect) with bone grafts. We present six patients with the Tessier no. 5 facial cleft who have been treated in our combined centers and discuss the surgical options and difficulties faced in the reconstruction of this rare and challenging craniofacial malformation. To date, we have treated six patients (two with bilateral and four with unilateral clefts). Three of the patients with unilateral clefting had an associated no. 4 cleft and one patient with a bilateral cleft had an associated no. 3 cleft. This paper represents the largest series to date documenting surgery for patients with the Tessier no. 5 facial cleft.

Novel mutations of the BSCL2 and AGPAT2 genes in 10 families with Berardinelli-Seip congenital generalized lipodystrophy syndrome

P>Context Congenital generalized lipodystrophy, or Berardinelli-Seip syndrome, is a rare autosomal recessive disease caused by mutations in either the BSCL2 or AGPAT2 genes. This syndrome is characterized by an almost complete loss of adipose tissue usually diagnosed at birth or early infancy resulting in apparent muscle hypertrophy. Common clinical features are acanthosis nigricans, hepatomegaly with or without splenomegaly and high stature. Acromegaloid features, cardiomyopathy and mental retardation can also be present. Design We investigated 11 kindreds from different geographical areas of Brazil (northeast and southeast). All coding regions as well as flanking intronic regions of both genes were examined. Polymerase chain reaction (PCR) amplifications were performed using primers described previously and PCR products were sequenced directly. Results Four AGPAT2 and two BSCL2 families harboured the same set of mutations. BSCL2 gene mutations were found in the homozygous form in four kindreds (c.412C > T c.464T > C, c.518-519insA, IVS5-2A > G), and in two kindreds compound mutations were found (c.1363C > T, c.424A > G). In the other four families, one mutation of the AGPAT2 gene was found (IVS3-1G > C and c.299G > A). Conclusions We have demonstrated four novel mutations of the BSCL2 and AGPAT2 genes responsible for Berardinelli-Seip syndrome and Brunzell syndrome (AGPAT2-related syndrome).

The p.A2215D Thyroglobulin Gene Mutation Leads to Deficient Synthesis and Secretion of the Mutated Protein and Congenital Hypothyroidism with Wide Phenotype Variation

Context: Thyroglobulin (TG) is a large glycoprotein and functions as a matrix for thyroid hormone synthesis. TG gene mutations give rise to goitrous congenital hypothyroidism (CH) with considerable phenotype variation. Objectives: The aim of the study was to report the genetic screening of 15 patients with CH due to TG gene mutations and to perform functional analysis of the p. A2215D mutation. Design: Clinical evaluation and DNA sequencing of the TG gene were performed in all patients. TG expression was analyzed in the goitrous tissue of one patient. Human cells were transfected with expression vectors containing mutated and wild-type human TG cDNA. Results: All patients had an absent rise of serum TG after stimulation with recombinant human TSH. Sequence analysis revealed three previously described mutations (p. A2215D, p. R277X, and g. IVS30 + 1G > T), and two novel mutations (p. Q2142X and g. IVS46-1G > A). Two known (g. IVS30 + 1G/p. A2215D and p. A2215D/p. R277X) and one novel (p. R277X/g. IVS46-1G > A) compound heterozygous constellations were also identified. Functional analysis indicated deficiency in TG synthesis, reduction of TG secretion, and retention of the mutant TG within the cell, leading to an endoplasmic reticulum storage disease, whereas small amounts of mutant TG were still secreted within the cell system. Conclusion: All studied patients were either homozygous or heterozygous for TG gene mutations. Two novel mutations have been detected, and we show that TG mutation p. A2215D promotes the retention of TG within the endoplasmic reticulum and reduces TG synthesis and secretion, causing mild hypothyroidism. In the presence of sufficient iodine supply, some patients with TG mutations are able to compensate the impaired hormonogenesis and generate thyroid hormone. (J Clin Endocrinol Metab 94: 2938-2944, 2009)