Annamaria Perri

Turner's syndrome: cardiologic profile according to the different chromosomal patterns and long-term clinical follow-Up of 136 nonpreselected patients.

The preferential association between Turners syndrome and congenital heart defects (CHD) have been well known since the first description by Morgagni. There are few studies about the different cardiologic problems stemming from different chromosomal patterns of X monosomies. We reviewed a large series of 136 patients with Turner syndrome without cardiologic preselection, 29 of whom had some kind of CHD (21.5%). Partial anomalous pulmonary venous drainage (PAPVD; 2.9%), aortic valve disease (stenosis and/or incompetence) (AoVD; 5.1%), aortic coarctation (AoCo; 4.4%), and bicuspid aortic valve (BicAo; 14.7%) are much more frequent in Turners syndrome than in the normal population, with the difference being statistically highly significant. In our cases, only the 45, X subjects showed severe CHD and multiple lesions, whereas the X-ring pattern was associated with an elevated prevalence of BicAo. Patients with X-deletion showed no signs of congenital heart malformations. Eleven patients, all with 45, X pattern, and significant CHD, underwent cardiac surgery at a mean age of 7.7 ± 5.3 years (range 7 days–18 years) without complications. At follow-up of 3–18 years (8.6 ± 5.2), we were unable to observe any type of evolution of the remaining untreated cardiovascular anomalies.

Pelvic ultrasonography in patients with Turner syndrome: Age-related findings in different karyotypes

Real-time ultrasonography was performed in 142 patients with Turner syndrome, aged 0.57 to 21 years, with different karyotypes (45,X [4896], X mosaicism [17%], and X structural abnormalities [35%]). Ovarian and uterine volumes were calculated and the data collected in a mixed longitudinal and cross-sectional mode. Thirty-eight patients were followed longitudinally during pubertal age (10 to 18 years bone age) for ovarian data. Patients with Turner syndrome were divided into two groups according to the presence or absence of detectable ovaries. Patients with Turner syndrome with detectable ovaries showed the first increase in ovarian volume at about 9 years of bone age; this increase was continuous and more evident only after 14 years of age and appeared later than in control subjects. When followed longitudinally during puberty, the ovaries showed a hormonal function in some cases. Girls with X mosaicism had the highest percentage of bilateral detectable ovaries and the greatest total ovarian volume; about 50% of them had spontaneous breast appearance and 38.5% had spontaneous menarche. They showed also the lowest gonadotropin levels, when bilateral ovaries were present during puberty. On the contrary, patients with the 45,X karyotype had the lowest percentage of detectable ovaries, ovarian volume, and spontaneous breast appearance. In our patients with Turner syndrome, uterine measures increased significantly with age and this was more evident in subjects with detectable ovaries after 13 years of bone age. Compared with control subjects, they showed significantly lower uterine measures, and patients with X mosaicism had greater and more progressive increments. In conclusion, pelvic ultrasonography in Turner syndrome is particularly useful in detecting ovaries and their possible increase in volume. These data, linked with karyotype pattern and gonadotropin levels, have prognostic value in predicting the future sexual development of these patients.

Barber-Say syndrome: Report of a new case

We present a girl with lax, redundant skin, ectropion, bulbous nose, macrostomia, and absence of mammary glands. To our knowledge, she represents the fourth described case of Barber-Say Syndrome (BSS). BSS and ablepharon macrostomia syndrome (AMS) share common and distinctive clinical manifestations that involve the same structure of the skin and adnexa. We hypothesize that they may derive from a defective regulation of the same gene.

GH Therapy and first final height data in Noonan‐like syndrome with loose anagen hair (Mazzanti syndrome)

Noonan‐like syndrome with loose anagen hair (NS/LAH or Mazzanti Syndrome) is caused by a single missense mutation in SHOC2 promoting tN‐myristoylation of the encoded protein. Cardinal features include facial features resembling NS, short stature often associated with proven growth hormone deficiency (GHD), typical ectodermal anomalies, and distinctive behavior. Overall, the clinical features are more severe than those generally observed in NS, even though the phenotype improves with age. We report on growth and pubertal trend in seven patients heterozygous for a mutated SHOC2 allele, treated with long‐term GH‐therapy, and final height (FH) in three of them. They were approximately −3 SDS below the Italian general population standards, they had very low IGF1 levels at baseline and GHD at pharmacological tests. All patients were treated with GH (0.035 mg/kg/day) for a mean period of 8.49 ± 5.72 years. After the 1st year of GH‐therapy, IGF1 level and height velocity had increased. Three of 7 patients reached the FH (−2.34 ± 0.12 SDS) at 18.25 ± 0.73 years, after GH administration for 12.39 ± 2.12 years. Pubertal development was variable, showing a prolonged and delayed puberty or rapid pubertal progression that could impair the FH. Overall, our data in this small cohort suggest that NS/LAH patients benefit from long‐term GH‐therapy, although they do not show the characteristic catch‐up growth of isolated GHD. While the observed growth and pubertal behavior is consistent with a dysfunction of the hypothalamic‐pituitary‐gonadal axis, the functional link between SHOC2 and the GH/IGF signaling pathways remains to be clarified.

Response to long-term growth hormone therapy in patients affected by RASopathies and growth hormone deficiency: Patterns of growth, puberty and final height data.

RASopathies are developmental disorders caused by heterozygous germline mutations in genes encoding proteins in the RAS‐MAPK signaling pathway. Reduced growth is a common feature. Several studies generated data on growth, final height (FH), and height velocity (HV) after growth hormone (GH) treatment in patients with these disorders, particularly in Noonan syndrome, the most common RASopathy. These studies, however, refer to heterogeneous cohorts in terms of molecular information, GH status, age at start and length of therapy, and GH dosage. This work reports growth data in 88 patients affected by RASopathies with molecularly confirmed diagnosis, together with statistics on body proportions, pubertal pattern, and FH in 33, including 16 treated with GH therapy for proven GH deficiency. Thirty‐three patients showed GH deficiency after pharmacological tests, and were GH‐treated for an average period of 6.8 ± 4.8 years. Before starting therapy, HV was −2.6 ± 1.3 SDS, and mean basal IGF1 levels were −2.0 ± 1.1 SDS. Long‐term GH therapy, starting early during childhood, resulted in a positive height response compared with untreated patients (1.3 SDS in terms of height‐gain), normalizing FH for Ranke standards but not for general population and Target Height. Pubertal timing negatively affected pubertal growth spurt and FH, with IGF1 standardized score increased from −2.43 to −0.27 SDS. During GH treatment, no significant change in bone age velocity, body proportions, or cardiovascular function was observed.

New insights on diabetes in Turner syndrome: results from an observational study in adulthood

ObjectiveTo explore the characteristics of diabetes mellitus in adults with Turner syndrome.DesignObservational study consisting of a prospective phase after the access of adults with Turner syndrome to the Endocrinology Unit (median period of follow-up 15.6, interquartile range: 12.0–24.5 months) and a retrospective collection of data from the diagnosis of Turner syndrome until the time of access to the Endocrinology Unit. A total of 113 Italian Turner syndrome patients were included in the study. During the prospective phase of the study, each patient underwent physical examination, fasting blood sampling, and an oral glucose tolerance test on a yearly basis. Oral glucose tolerance test was used to perform the diagnosis of diabetes mellitus.ResultsBefore access to the Endocrinology Unit, diabetes mellitus was diagnosed in two Turner syndrome patients. Another five cases of diabetes mellitus were diagnosed at the first access to the Endocrinology Unit, whereas seven new cases of diabetes mellitus were diagnosed during the prospective phase of the study. At the diagnosis of diabetes mellitus, only one patient had fasting glucose above 126 mg/dL, and only two had an HbA1c value >6.5% (48 mmol/mol). When compared to normo-glucose tolerant patients, the diabetic patients had a significantly lower insulin-to-glucose ratio at 30 and 60 min of the oral glucose tolerance test. In the regression analyses, only age was associated with the development of diabetes mellitus.ConclusionsThis study confirms that diabetes mellitus is frequent in Turner syndrome and suggests that it is specific to the syndrome. In addition, this study demonstrates that oral glucose tolerance test is a more sensitive test than HbA1c for the diagnosis of diabetes mellitus in Turner syndrome.