Oculo-auriculo-vertebral spectrum in Klinefelter syndrome.

We report a boy with classical 47,XXY Klinefelter syndrome (KS) and oculo-auriculo-vertebral spectrum (OAV). Two patients with KS and OAV were reported previously. Also, the combination of bilateral aplasia of the mandibular ramus and condyle and KS has been documented. The present observation supports the view that the cause of hemifacial microsomia appears heterogeneous and that OAV may be part of the spectrum of craniofacial anomalies associated with KS.

Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1.

Five percent of individuals with neurofibromatosis type 1 (NF1) present with congenital long bone pseudarthrosis (PA). In large series, 50-80% of patients with congenital long bone PA also have NF1. Very little information exists on the natural history and pathogenesis of PA in NF1. This report is a descriptive analysis of a large series of patients with NF1 and tibial bowing or PA. Study A is a case-control study using the National Neurofibromatosis Foundation International Database (NNFFID). Eighty-five patients with PA were compared to a control group from the same database. There was a statistically significant male predominance of NF1 cases with PA (54 males to 31 females), compared to controls (85 males to 87 females) (chi2 = 4.0, P = 0.046, using a two-tailed test with Yates' correction). There was no significant difference in the clinical presentation of NF1 manifestations in NF1 patients with PA than in NF1 patients without PA. Of the affected individuals with PA, there were 24 de novo cases and 21 familial cases (9 through maternal and 12 through paternal inheritance). Questions that could not be answered by Study A were addressed by a partially overlapping case-series report, Study B, in which data on 75 cases ascertained through questionnaires completed by NF center directors were collected. From Study B we determined that half of the patients who had a fracture sustained it before age 2, and approximately 16% of the pseudarthrosis patients had an amputation. Our data indicate a male predominance and no parent-of-origin effect. Male gender may be a susceptibility factor for pseudarthrosis in NF1.

Scanning the first part of the neurofibromatosis type 1 gene by RNA-SSCP: identification of three novel mutations and of two new polymorphisms.

Neurofibromatosis type 1 (NF1) of von Recklinghausen is a common autosomal dominant disorder, characterized by peripheral neurofibromas, café-au-lait spots and Lisch nodules of the iris. The high mutation rate at the NF1 locus results in a wide range of molecular abnormalities. We have scanned 14 different exons from the first part of the NF1 gene using the RNA-single strand conformation polymorphism (RNA-SSCP) method in a series of 40 NF1 patients. Three novel mutations, two nonsense and one missense, and two polymorphisms have been detected in familial cases. Genotype-phenotype correlations have been investigated, but no particular association has been detected. After this screening, the majority of NF1 chromosomes has not yet been characterized, confirming the difficulty in detecting the defect underlying NF1 in most families, even following extensive DNA analysis.

Screening of neurofibromatosis type 1 gene: identification of a large deletion and of an intronic variant.

Neurofibromatosis type 1 of von Recklinghausen is a common autosomal dominant disorder, characterized by peripheral neurofibromas, café-au-lait spots and Lisch nodules of the iris. The high mutation rate at the neurofibromatosis type 1 locus results in a wide range of molecular abnormalities. We have screened seven different exons of the neurofibromatosis type 1 gene, including those codifying for the GAP-related domain, using the RNA-Single Strand Conformation Polymorphism (RNA-SSCP) method in a series of 59 neurofibromatosis type 1 patients. We have also analyzed four intragenic repeats and one RFLP to detect hemizygosity and evaluate informativeness in at-risk families. One deletion and a new intronic normal variant have been detected. Thus the majority of Neurofibromatosis type 1 chromosomes have not been characterized, confirming difficulty in providing proper genetic counselling in neurofibromatosis type 1 families, even following extensive DNA analysis.

Hypertension in children with neurofibromatosis.

Hypertension in neurofibromatosis is mostly a consequence of a stenosis of the renal artery or is due to phaeochromocytoma. Riccardi pointed out primary hypertension in patients with several cervical neurofibromas in the absence of phaeochromocytoma and he noticed that the elevation of BP was often already present in children. Nine (15.8%) of 57 neurofibromatosis patients (age from 1.5 to 23 years) examined, presented BP levels above the 95th percentile on several occasions and three in particular had severe hypertension with compromised target organs. Two of them had a stenosis of the renal artery, in the third an organic origin of hypertension was not demonstrated, but there was an asymptomatic glioma of the hypothalamus. The other six children had a labile or borderline hypertension and two of them had, respectively, a glioma of the thalamus and of the optical chiasm. Elevation of the catecholamine metabolites or other causes of hypertension were not found in any of these patients. These preliminary data show a high incidence of hypertension in neurofibromatosis, primary or due to organic causes and overall they point out a possible correlation between hypertension and cerebral neoplasia.

[The association between hypothyroidism and other congenital defects. The experience of the National Registry in 1987-1992]. / Associazione tra ipotiroidismo e altri difetti congeniti. L'esperienza del Registro Nazionale negli anni 1987-1992.

This study considers the birth defects (BD) observed from 1987 to 1992 in 35/811 newborns with congenital hypothyroidism (CH) diagnosed by neonatal screening and included in the National Register. The BD incidence was higher than in the general population (4.3 vs 2.5-3%) and especially the one of the congenital heart diseases, (CHD) (2.1 vs 0.3-0.8%). Furthermore the CHD were more frequently observed in females than in males (M/F = 1/4.7). These results seem not to be casual but the reasons remain unknown. The most frequent CHD observed were the septal defects and the pulmonary stenosis. Further are presented and discussed the main findings of 2 groups of CH patients (with and without BD). These results are a good instance of the National Register applications, also for less known aspects of the CH like the concomitant BD.

[Neonatal screening in congenital hypothyroidism in Italy. The National Registry]. / Lo screening neonatale dell'ipotiroidismo congenito in Italia. Il Registro Nazionale.

Neonatal screening for congenital hypothyroidism (CH) began in Italy in 1977 and then progressively developed covering 97% of live births in 1992. The National Register of infants with congenital hypothyroidism was established in 1987 as a project of the Health Ministry and is coordinated by the Italian Institute of Health. The aim of the Register is to provide disease surveillance, to monitor the efficiency and effectiveness of neonatal screening and to allow the identification of possible etiological risk factors in congenital hypothyroidism. The results of the Register provided valuable epidemiological informations about congenital hypothyroidism in Italy and evidenced several areas in whom an increased incidence probably caused by iodine deficiency was observed. Discussion of Register data during annual national meetings has allowed an improvement of the screening program with particular regard to the beginning of therapy with L-thyroxine and its dose. Because of the wide spectrum of collected information, the National Register represents a useful tool for developing of collaborative studies concerning some aspects of CH not yet completely elucidated.

The National Register of infants with congenital hypothyroidism detected by neonatal screening in Italy.

Neonatal screening for congenital hypothyroidism began in Italy in 1977 and then progressively developed covering 94% of live births in 1991. The National Register of infants with congenital hypothyroidism was established in 1987 as a project of the Health Ministry. The results of the Register provided valuable epidemiological information about congenital hypothyroidism in Italy and evidenced some aspects in the screening organization which had to be improved. Discussion of Register data during annual national meetings has recently allowed an improvement of the screening program with particular regard to the beginning of therapy with L-thyroxine and its dose.

[The follow-up of malformation syndromes: the new frontier]. / Il follow-up delle sindromi malformative: la nuova frontiera.

Much progress has been made over the last decade in the field of genetic diseases, mainly because of the advances in molecular biology. However, this has not been paralleled by similar progress in the assistance provided for such patients, owing to the lack of adequate follow-up of such chronic disorders. The author analyses the main objectives of the follow-up.

[National Register of congenital hypothyroidism]. / Il registro nazionale degli ipotiroidei congeniti.

The results of five years activity of the National Register of children with Congenital Hypothyroidism (NRCH) have been evaluated. NRCH was established in Italy in 1987, as a pilot project of Health Ministry. All Italian Centers in charge of the screening, treatment and follow-up of CH are involved in the program. The results have provided further epidemiological informations about CH in Italy and have evidenced some aspects in the screening organization which had to be improved. Discussion of Register data in annual meetings has recently allowed to obtain an improvement especially for the beginning of treatment and the used dose of therapy.

Three years of experience of the congenital hypothyroidism National Register.

Mental retardation caused by congenital deficiency of thyroid hormones can be prevented by early diagnosis and therapy which are assured by neonatal thyroid screening. Congenital hypothyroidism screening is performed in Italy by regional centres which in 1989 have screened more than 82% of neonatal population. Since 1987 a National Register of children affected by CH has been instituted. The results of the analysis of data collected in the first three years are reported.

Pulsatile growth hormone release in Turner's syndrome and short normal children.

To determine whether the quantitative and qualitative aspects of GH secretion in girls with Turner's syndrome are similar to those of short-normal children we studied the 24-h GH secretion of 10 patients with Turner's syndrome and 9 short-normal children with comparable auxological features. GH profiles, obtained by 30-min sampling, were analysed by the Pulsar programme. The pulsatile GH release over the 24 h in Turner's syndrome was similar to that in normal children. However, when the GH release over the 12 day and night hours were separately analysed, only normal children showed a night-time increase in the sum of peak amplitudes. Moreover, patients with Turner's syndrome had significantly decreased number and frequency of peaks in the night-time compared with short children. In short-normal children but not in Turner's syndrome, height velocity was related to the 24-h integrated concentration of GH, area under the curve over zero-line and over baseline, sum of peak areas, and amplitudes. Night-time GH area over zero-line and over baseline, mean peak amplitude, height area, sum of peak area and amplitudes were positively correlated with height velocity in short children, whereas in Turner's syndrome height velocity was related to daytime parameters only. In conclusion, girls with Turner's syndrome have a discrete pattern of pulsatile GH release. However, the relation of GH secretion to growth in these patients, is uncertain.

Periaqueductal gliosis causing hydrocephalus in a patient with neurofibromatosis type 1.

We present a case of primary nontumoral aqueductal stenosis associated with neurofibromatosis type 1 (NF-1) in an asymptomatic 11-year-old boy. The diagnosis of hydrocephalus followed the finding of bilateral papilledema at an ocular assessment and the diagnosis of NF-1 was made during hospitalization for the papilledema. Periaqueductal gliosis was suspected on cerebral T2-weighted magnetic resonance imaging (MRI). We believe that the incidence of hydrocephalus due to nontumoral aqueductal stenosis has been underestimated in NF-1. We emphasize the importance of early diagnosis of NF-1 and prompt evaluation in order to recognize this complication. In this regard MRI scanning offers more diagnostic advantages over other investigations. Forty-seven previously described cases have been collected from the literature.

Blood pressure behaviour and control in Turner syndrome.

UNLABELLED: Adult Turner syndrome (TS) patients frequently present hypertension. To clarify the pathogenesis of this hypertension we examined the blood pressure (BP) behaviour and the renin-angiotensin-aldosterone system in 31 TS patients (2-22 years of age). BP levels were occasionally elevated in 47% of the subjects and constantly elevated in 23%. Most of the patients were on estrogen replacement therapy, but 26% of them presented with elevated levels since childhood. Supine and upright plasma renin activity (PRA) values were higher in TS compared to controls and more elevated in hypertensive TS than in the normotensive ones. At Captopril challenge TS showed different PRA responses regardless of the karyotype and clinical features. Patients on estrogen therapy, however, exhibited higher increments of PRA after Captopril. CONCLUSIONS: TS patients show high frequency of hypertension in pediatric age. Estrogen therapy is an outbreaking and worsening factor. An estrogen independent role of the renin-angiotensin-aldosterone system in the pathogenesis of TS hypertension is still uncertain.

Juvenile rheumatoid arthritis in Turner's syndrome.

An increased risk for autoimmune diseases has been recognized in Turner's syndrome (T.S.). However autoimmune rheumatic or connective tissue disorders have not been described. We report here on a 8-8/12 year old caucasian girl with T.S. and Juvenile Rheumatoid Arthritis (JRA). The hypothesis that the association is more than casual is discussed.

[Sex-linked inheritance in fronto-metaphyseal dysplasia]. / Hérédité liée au sexe dans la dysplasie fronto-mètaphysaire.

The author reports a family study of fronto-metaphyseal dysplasia in a 2 months-old child, in his mother and maternal grand-mother. The child is the more severely affected, while the mother and the grand-mother have less severe manifestations of the syndrome. This evidence permits to confirm the X-linked recessive inheritance of the disease, with severe manifestations in males and variable expression in female carriers.

Bilateral retinoblastoma with de novo constitutional balanced translocation t(2;9)(q11;p11).

The case of a 6-year-old boy with bilateral retinoblastoma (RB) and apparently de novo balanced translocation t(2;9)(q11;p11) is presented. The normality of 13q14 chromosome region has been confirmed using high resolution techniques and Esterase D assay. The hypothesis that this RB might be correlated to the translocation is discussed.