Corrigendum: Pubertal timing in children with Silver Russell syndrome compared to those born small for gestational age.

[This corrects the article DOI: 10.3389/fendo.2022.975511.].

Pubertal timing in children with Silver Russell syndrome compared to those born small for gestational age.

Context: Data on pubertal timing in Silver Russell syndrome (SRS) are limited. Design and methods: Retrospective observational study including twenty-three SRS patients [11p15 loss of methylation, (11p15 LOM, n=10) and maternal uniparental disomy of chromosome 7 (mUPD7, n=13)] and 21 small for gestational age (SGA). Clinical (thelarche in females; testis volume ≥ 4 ml in males; pubarche), BMI SD trend from the age of 5 to 9 years to the time of puberty, biochemical parameters of puberty onset [Luteinizing hormone (LH), 17-ß-estradiol, testosterone], and bone age progression were evaluated. Results: Pubertal onset and pubarche occurred significantly earlier in children with SRS than in SGA (p 0.03 and p 0.001, respectively) and clinical signs of puberty onset occurred earlier in mUPD7 than in 11p15LOM group (p 0.003). Five SRS children experienced central precocious puberty and LH, 17-ß-estradiol, testosterone were detected earlier in SRS than in SGA (p 0.01; p 0.0001). Bone age delay in SRS children was followed by rapid advancement; the delta between bone age and chronological age in SRS group became significantly higher than in SGA group at the age of 9-11 years (p 0.007). 11p15LOM patients were underweight at the age of 5 years and showed a progressive normalization of BMI that was significantly higher than in mUPD7 (p 0.04) and SGA groups (p 0.03) at puberty onset. Conclusion: Timing of puberty is affected in SRS and occurred earlier in mUPD7 compared to 11p15LOM. The impact of early puberty on adult height and metabolic status deserves long-term evaluation.

Sirolimus Restores Erythropoiesis and Controls Immune Dysregulation in a Child With Cartilage-Hair Hypoplasia: A Case Report.

Cartilage-hair hypoplasia (CHH) is a syndromic immunodeficiency characterized by metaphyseal dysplasia, cancer predisposition, and varying degrees of anemia. It may present as severe combined immunodeficiency in infancy, or slowly progress until fully manifesting in late adolescence/adulthood. No targeted treatment is currently available, and patients are usually managed with supportive measures, or are offered a bone marrow transplant if the clinical phenotype is severe and a suitable donor is available. We report the case of a young girl presenting with transfusion-dependent erythropoietic failure and immunological features resembling autoimmune lymphoproliferative syndrome who responded well to empirical sirolimus. She later developed a marked growth delay, which was ultimately attributed to metaphyseal dysplasia. A diagnosis of CHH was reached through whole-genome sequencing (WGS), after a less sensitive genetic diagnostic strategy failed. The patient eventually underwent a haploidentical bone marrow transplant due to progressive combined immunodeficiency manifested as cryptococcal meningoencephalitis. This case illustrates the potential role of sirolimus in correcting anemia and partially controlling the immune aberrations associated with CHH, and serves as a reminder of the invaluable role of WGS in diagnosing patients with complex and atypical presentations.

Cognitive and White Matter Microstructure Development in Congenital Hypothyroidism and Familial Thyroid Disorders.

CONTEXT: Children with congenital hypothyroidism (CH) are at risk for suboptimal neurodevelopment. OBJECTIVES: To evaluate neurocognitive function and white matter microstructure in children with permanent or transient CH and to correlate these findings with disease severity. DESIGN, PARTICIPANTS AND METHODS: A retrospective and prospective observational study was conducted in 39 children with permanent or transient CH, and in 39 healthy children. Cognitive function was assessed by Wechsler Intelligence Scale, Fourth Edition, and by other tests; the white matter microstructure was investigated by 3 Tesla magnetic resonance imaging. RESULTS: Children with permanent CH have lower cognitive scores at a median age of 9.5 years than those with transient CH and controls. An IQ score between 71 and 84 was found in 28.6% of permanent CH and of <70 (P = 0.06) in 10.7%. The Processing Speed Index (PSI; P = 0.004), sustained visual attention (P = 0.02), reading speed (P = 0.0001), written calculations (P = 0.002), and numerical knowledge (P = 0.0001) were significantly lower than controls. Children born to mothers with Hashimoto's thyroiditis have significantly lower IQ values (P = 0.02), Working Memory Index (P = 0.03), and PSI (P = 0.02). Significantly lower IQ and Verbal Comprehension Index values were found in children with a family history of thyroid disorders (P = 0.004 and P = 0.009, respectively). In children with permanent CH, significant correlations between abnormalities in white matter microstructural, clinical, and cognitive measures were documented. CONCLUSIONS: These findings indicate that children with CH are at risk of neurocognitive impairment and white matter abnormalities despite timely and adequate treatment. The association between offspring cognitive vulnerability and maternal thyroid disorders requires careful consideration.

Endocrine Outcomes In Central Diabetes Insipidus: the Predictive Value of Neuroimaging "Mismatch Pattern".

CONTEXT: The etiology of central diabetes insipidus (CDI) in children is often unknown. Clinical and radiological features at disease onset do not allow discrimination between idiopathic forms and other conditions or to predict anterior pituitary dysfunction. OBJECTIVE: To evaluate the evolution of pituitary stalk (PS) thickening and the pattern of contrast-enhancement in relation with etiological diagnosis and pituitary function. METHODS: We enrolled 39 children with CDI, 29 idiopathic and 10 with Langerhans cell histiocytosis (LCH). Brain magnetic resonance images taken at admission and during follow-up (332 studies) were examined, focusing on PS thickness, contrast-enhancement pattern, and pituitary gland size; T2-DRIVE and postcontrast T1-weighted images were analyzed. RESULTS: Seventeen of 29 patients (58.6%) with idiopathic CDI displayed "mismatch pattern," consisting in a discrepancy between PS thickness in T2-DRIVE and postcontrast T1-weighted images; neuroimaging findings became stable after its appearance, while "mismatch" appeared in LCH patients after chemotherapy. Patients with larger PS displayed mismatch more frequently (P = 0.003); in these patients, reduction of proximal and middle PS size was documented over time (P = 0.045 and P = 0.006). The pituitary gland was smaller in patients with mismatch (P < 0.0001). Patients with mismatch presented more frequently with at least one pituitary hormone defect, more often growth hormone deficiency (P = 0.033). CONCLUSIONS: The PS mismatch pattern characterizes patients with CDI, reduced pituitary gland size, and anterior pituitary dysfunction. The association of mismatch pattern with specific underlying conditions needs further investigation. As patients with mismatch show stabilization of PS size, we assume a prognostic role of this peculiar pattern, which could be used to lead follow-up.

Cognitive Profiles and Brain Volume Are Affected in Patients with Silver-Russell Syndrome.

CONTEXT: There is little information on cognitive function in Silver-Russell syndrome (SRS), and no neuroimaging studies are available so far. OBJECTIVE: To assess cognitive function and brain volumes in patients with SRS. DESIGN/SETTING: Wechsler Intelligence Scale and brain magnetic resonance on a 3-Tesla scanner with Voxel-based morphometry analysis were performed between 2016 and 2018 in a single tertiary university center. PARTECIPANTS: 38 white subjects with clinical diagnosis of SRS confirmed by molecular analysis: 30 of these patients (mean age 12.6 ± 10 years) were enrolled for cognitive assessment; 23 of the 30 performed neuroimaging sequences. A control group of 33 school-aged children performed cognitive assessment while 65 age and sex-matched volunteers were included for the neuroradiological assessment. MAIN OUTCOMES: Intelligence quotient, Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), Processing Speed Index, and brain volume. RESULTS: The mean overall IQ score was 87.2 ± 17, and it was significantly lower in the maternal uniparental disomy of chromosome 7 (mUPD7) group at the age of 6 to 16 years compared to loss of methylation on chromosome 11p15 (11p15 LOM) group and to controls. VCI, PRI, and WMI were significantly higher in 11p15 LOM group and in control group than in mUPD7 group at the age of 6 to 16 years. There were no significant differences in cognitive scores between 11p15 LOM school-aged patients and the control group. SRS patients showed lower brain volume compared to controls at the frontal/temporal poles and globi pallidi. CONCLUSIONS: Patients with mUPD7 had an impaired cognitive profile. The brain volume at the frontal/temporal lobes and at the globi pallidi was reduced in patients with SRS.