Focal nodular hyperplasia in a child with Beckwith–Wiedemann syndrome

Beckwith–Wiedemann Syndrome (BWS) is associated with somatic overgrowth and a high risk for embryonal tumors, including hepatoblastoma, a highly malignant liver tumor of childhood. Focal nodular hyperplasia (FNH), on the other hand, is a benign tumor of the liver that is uncommon in childhood. Herein we describe a case of FNH in a child with BWS, the first such report in the literature.     

Epilepsy in Aicardi–Goutières syndrome

BackgroundAicardi–Goutières syndrome (AGS) is a genetically determined early-onset encephalopathy with variable phenotype, including neurologic manifestations such as dystonia, spasticity, epileptic seizures, progressive microcephaly, and severe developmental delay. The aim of our study was the characterization of epilepsy, one of the most frequent and severe AGS manifestations, in molecularly confirmed patients.MethodsWe reviewed the medical records, EEG, and CT/MRI findings in 16 patients aged 1–22 years that carried AGS1-5 mutations.ResultsEpilepsy manifested in 12 (75%) patients and took a refractory course in 9 (56%). 4 (25%) patients presented with seizures in the first four weeks and 11 (69%) altogether in the first year of life. Spasms were reported in 3 (19%) patients, focal seizures in 4 (25%), myoclonic in 5 (31%), symmetric or asymmetric tonic in 11 (69%), generalized tonic–clonic in 3 (19%) and status epilepticus in 4 (25%). EEG recordings initially showed a slow and disorganized background, followed by a regional intermittent theta/delta slow, while obvious multifocal or generalized epileptic discharges were only observed at follow-up. None of these EEG features were specific of AGS. There was no discernible correlation between the genotype and epilepsy onset, seizure types and epilepsy evolution. Epilepsy severity did not correspond to neuroimaging pathology.DiscussionEpilepsy constitutes a cardinal feature of AGS, characterized by early onset, predominantly tonic semiology and a refractory course. The early discrimination of epileptic seizures from paroxysmal dystonia poses a challenge for neuropaediatricians, considering the initially inconspicuous or non-specific EEG findings. This study underlines the necessity of a more systematic serial evaluation of AGS patients using long-term video-EEG recordings.     

Virilizing adrenal tumour mimicking congenital adrenal hyperplasia with P450c11 (11β-hydroxylase) deficiency

In a girl aged 5 years with a virilizing adrenal adenoma the urinary and plasma steroid findings suggested the diagnosis of congenital adrenal hyperplasia due to P450c11 (11-hydroxylase) deficiency. After removal of the tumour clinical signs receded and the hormonal values normalized. RNA analysis of the tumour tissue revealed low amounts of P450c11 mRNA which indicates that P450c11 deficiency of the adenoma caused the steroid abnormalities in this girl.Presented in part at the 31st annual meeting of the European Society for Paediatric Endocrinology, Zaragoza, Spain, September 6–9th, 1992 [25]     

Progress in molecular-genetic studies on congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Background  11β-hydroxylase deficiency is one of the main causes of congenital adrenal hyperplasia (CAH). It is caused by the mutation of the CYP11B1 gene that encodes the enzyme. Researches have shown that mutations of the CYP11B1 gene would result in activity decrease or inactivation of the enzyme in classical 11β-hydroxylase deficiency. Data sources  Articles on CAH and CYP11B1 gene mutation were retrieved from PubMed and MEDLINE published after 1991. Results  The prevalence, pathophysiology, and molecular-genetic mechanisms were summarized. Conclusions  The disease is caused by genetic mutations of CYP11B1, and types of the mutations are varied. In classical 11β-hydroxylase deficiency, genetic mutations of CYP11B1 lead to activity decrease or loss; mutations in unclassical 11β-hydroxylase deficiency are not definite. And the relationship between genotype and phenotype is not established.     

Does common channel length affect surgical choice in female congenital adrenal hyperplasia patients?

ObjectivePartial/total urogenital sinus mobilization (UGSM) is one of the recommended techniques for treatment of female congenital adrenal hyperplasia (CAH). In this study we compared the length of common channel (CC) and type of operation performed in CAH patients.Patients and methodsWe retrospectively analyzed data of patients receiving surgery for female CAH. Patients were separated into three groups: group 1 had partial UGSM, group 2 had total UGSM, and group 3 had total UGSM plus the vaginal anterior wall was made from CC. Age at surgery, length of CC, surgical time, follow-up time, and complications were compared.ResultsThere were a total of 29 patients. For groups 1, 2, and 3, the average age at surgery was 47.2 months, 14.4 months, and 21.3 months, respectively, and the average CC length was 1.25 cm, 3.1 cm, 4.3 cm, respectively. The average time of surgery was 165 min, 193.1 min, 282.5 min, respectively. The average follow-up time was 34.7 months, 36.3 months, 28.3 months, respectively. There were two complications (UGS flap necrosis and opening of sutures) in the third group.ConclusionWe advise the use of partial UGSM for CC of 0.5–2 cm, total UGSM for CC of 2.5–3.5 cm, and total USM with use of CC as the anterior vaginal wall in CC ≥ 4 cm in length. Good cosmetic and functional results are obtained with this approach.     

Clinical and radiological findings in Schinzel–Giedion syndrome

The absence of a definitive genetic test for the autosomal recessive condition Schinzel–Giedion syndrome is a significant handicap to the recognition of this disorder. Radiological features have been an important aspect of many of the published cases. In a series of six cases, we now establish a consistency among many of the radiological features in affected cases which will be an important diagnostic aid in identifying future cases. This is confirmed by reference to an extensive review of previously published instances of the syndrome. Moreover, the clinical data, including previously unpublished photographs, which we detail from our patients will assist in enhanced diagnosis in the future.     

Vascular malformation and choroid plexus adrenal heterotopia: new findings in Beckwith-Wiedemann syndrome?

Large congenital arteriovenous malformations (AVM) may result in heart failure and death. We are reporting such combination with the AVM localized to the right thoracobrachial region. Remarkable postmortem findings included right renal and adrenal hemihyperplasia; the right adrenal fetal cortex presenting cytomegaly, endocrine pancreas hyperplasia, and heterotopic adrenal cortex with cytomegaly in the left lateral ventricle choroids plexus. The combination appears to be unique. The only previously reported example of adrenal cortex in the choroid plexus presented several features strongly suggestive of Beckwith-Wiedemann syndrome. Therefore, we postulate that additional uncommon findings in Beckwith-Wiedemann syndrome may include arteriovenous malformations and heterotopic adrenal tissue in choroids plexus.     

Kaposi’s sarcoma in a child with Wiskott-Aldrich syndrome

Introduction Kaposi’s sarcoma (KS) is rare in childhood. It may be favored by acquired immune deficiencies, but the predisposing factors to KS in other children are unclear.Discussion KS has been reported in only two children and one adult with primary immunodeficiency. We report here a Tunisian child with a Wiskott-Aldrich syndrome who developed KS at the age of 14 months.Conclusion This observation expands the spectrum of primary immunodeficiencies associated with KS in childhood.     

Guillain-Barré syndrome in a child with normal tendon reflexes

We describe the case of a 10-year-old child with the acute motor axonal neuropathy (AMAN) form of Guillain-Barré syndrome (GBS) with preserved tendon reflexes, 6 days after a bout of gastroenteritis. The child quickly showed weakness of the distal muscles of his four limbs, with preserved tendon reflexes and a raised CSF protein concentration with no cells. Nerve conduction studies showing motor axonal degeneration confirmed the diagnosis of GBS in spite of preserved tendon reflexes. The serum was positive for IgG antibodies to gangliosides GM1 and GD1b. The child received intravenous immunoglobulins, which resulted in a favorable progression. This case proves that GBS with normal tendon reflexes exists. The other cases of SGB with preserved tendon reflexes already described in the literature were the AMANs form with antibodies to gangliosides in the serum and only adults were affected.     

15β-Hydroxylated steroids may be diagnostically misleading in confirming congenital adrenal hyperplasia suspected by a newborn screening programme

In a Swiss screening programme for detection of congenital adrenal hyperplasia (CAH), 27 of over 120,000 newborns examined from 1992 to 1994 were further studied because of persistingly high 17 hydroxyprogesterone (17OHP). Out of 27, 11 were later confirmed to have CAH by specific gas chromatography of urinary steroids and ACTH test at age 3–4 months. Of 27, 11 were born at term (7 confirmed 21-hydroxylase deficiency, one 11-hydroxylase deficiency). Out of 27, 16 were preterm newborns. Of them, only 2 were confirmed to have CAH (one 21-, one 11-hydroxylase deficiency). In 3 cases with high 17OHP, but later not confirmed CAH, what appeared to be a pregnanetriolone peak in the gas chromatograms was shown to be 3, 15, 17-pregnenetriol. This compound may be misleading in confirming the diagnosis of CAH. 15-Hydroxylated compounds occur in fetuses, neonates, and amniotic fluid. Since human tissues do not have l5-hydroxylating capacity, their origin is unclear. However, since some bacteria (Bacillus megatherium) and mycelial fungi (fusaria) are known to hydroxylate steroids in position 15, it is likely that this compound is formed by micro-organisms in the enterohepatic circulation of newborns or their mothers.Presented in part as an invited lecture at the symposium on congenital adrenal hyperplasia in honour of Claude Migeon, Baltimore MD, June 11.–13., 1995, and at the 34th Annual Meeting of the European Society for Paediatric Endocrinology, Edinburgh UK, June 25–28, 1995     

Is basal serum 17-OH progesterone a reliable parameter to predict nonclassical congenital adrenal hyperplasia in premature adrenarche?

To determine the critical features for the diagnosis of nonclassical 21 hydroxylase deficiency (NC210HD) without performing adrenocorticotropic hormone (ACTH) test, we studied 186 cases with premature adrenarche. Clinical and laboratory features as well as basal 17-hydroxyprogesterone (17-OHP) were analyzed to determine factors important for differentiating NC21OHD. Overall, 6 patients (3.2%) had ACTH-stimulated 17-OHP > 10 ng/ml. A cutoff level of 2 ng/ml for basal 17-OHP was 66.7% sensitive and 78% specific for NC21OHD; however, a cutoff level of 1.55 ng/ml had higher sensitivity (83%) and specificity (70.6%). A cutoff of 1.55 ng/ml would lead to 31% of cases with premature adrenarche having to undergo ACTH test, and only one case would have been missed. That case had a bone age SDS > 2. Three cases out of five with a basal 17-OHP > 5 ng/ml had stimulated 17-OHP < 10 ng/ml. A cutoff of 1.55 ng/ml for basal 17-OHP together with bone SDS > 2 in those with lower basal levels as a guide for carrying out an ACTH test may yield better results in the diagnosis of NC21OHD in the premature adrenarche population. A cutoff of 5 ng/ml for basal 17-OHP should not be used for diagnosis of NC21OHD.     

Decrease of renal aquaporins 1–4 is associated with renal function impairment in pediatric congenital hydronephrosis

Background

Renal aquaporins (AQP1-4) concentration is downregulated and is in proportion to the degree of hydronephrosis graded by ultrasound in pediatric congenital hydronephrosis (CH). However, the relationship between the expression of AQP1-4 with the changes of renal function impairment (RFI) evaluated by ^99mTc-DTPA renal dynamic imaging is still unclear. This study aimed to investigate the relationship between AQP1-4 expression and degree of RFI in children with CH.

Methods

The expression of AQP1-4 was evaluated in 45 children with unilateral ureteropelvic junction obstruction (28 boys and 17 girls, average age: 28±10 months) and 15 children undergoing nephrectomy for nephroblastoma (8 boys and 7 girls, average age: 26±8 months) by immunoblotting and immunohistochemistry. Renal function was graded into mild and severe RFI by ^99mTc-DTPA renal dynamic imaging.

Results

One-way analysis of variance with Bonferonni??s correction showed a significantly reduced protein expression of AQP1?C4 in the severe RFI group compared with those in both mild RFI group and controls (AQP1: 0.52±0.09 vs. 0.91±0.06 vs. 1.23±0.033; AQP2: 0.68±0.12 vs. 1.09±0.06 vs. 1.52±0.08; AQP3: 0.59±0.16 vs. 0.94±0.08 vs. 1.31±0.07; AQP4: 0.64±0.06 vs. 1.14±0.07 vs. 1.61±0.07; P<0.001, respectively). In kidneys with severe RFI, there was a reduction in the protein concentration of all four AQP isoforms which was more pronounced compared with those seen in kidneys with mild RFI and in the controls.

Conclusion

AQP1-4 expression is reduced in proportion with the impairment degree of renal function graded by ^99mTc-DTPA renal dynamic imaging in human CH.     

Caroli’s syndrome with ureterovesical calculi in a young child

An 18-month-old boy was admitted with fever, abdominal pain, and hepatomegaly. CT scan revealed dilatation of intrahepatic biliary radicals with central dot sign, bilateral nephrocalcinosis, multiple ureteric and urinary bladder stones and right-sided obstructive hydroureteronephrosis due to a ureterovesical calculus of about 1.5 cm. Liver biopsy showed early hepatic fibrosis.     

Mycoplasma pneumoniae associated opsoclonus–myoclonus syndrome in three cases

Opsoclonus–myoclonus syndrome (OMS) is a rare acquired movement disorder occurring in all age groups, predominantly in infants. Although the exact pathogenesis is still undefined, there is strong evidence for a paraneoplastic or parainfectious immune process resulting in central nervous system dysfunction. Mycoplasma pneumoniae has been implicated in a number of immune-mediated neurologic diseases [28]. However, the association of M. pneumoniae and opsoclonus–myoclonus–ataxia syndrome is not well established so far. We present three cases with opsoclonus–myoclonus–ataxia syndrome in adolescents following an infection with M. pneumoniae. Monophasic disease course and full recovery correspond to the favorable prognosis known from parainfectious cases in young adults. This should affect therapeutic consideration. OMS should be added to the spectrum of M. pneumoniae-associated neurologic complications. Nevertheless, neuroblastoma has to be ruled out in all cases of OMS.     

Guillain-Barré syndrome associated with Legionnella infection

This is the first report of Guillain-Barré syndrome (GBS) related to Legionnella pneumophilia infection. A 13-year-old boy presented with acute dysphagia and dyspnea. He lived in a rural area and had a history of drinking potable deep-hole water. The patient was intubated because of increased respiratory distress. A positive direct fluoresein antigen test confirmed L. pneumophilia infection in BAL. One week after the first admission, acute weakness was noticed including the lower extremities and was more prominent in the distal than the proximal portions. GBS was considered as the initial diagnosis. Tests for all causes known to trigger GBS were negative. Specific serology for L. pneumophilia IgG was positive. He was treated with intravenous immunoglobulins and discharged with minor weakness and difficulty in walking in the second month. On the basis of this case, L. pneumophilia should be included in the etiologic spectrum of GBS.