High prevalence of syndromic disorders in patients with non-isolated central precocious puberty

Objective Non-idiopathic CPP is caused by acquired or congenital hypothalamic lesions visible on MRI or is associated with various complex genetic and/or syndromic disorders. This study investigated the different types and prevalence of non-isolated CPP phenotypes. Design and Methods This observational cohort study included all patients identified as having non-idiopathic CPP in the database of a single academic pediatric care center over a period of 11.5 years. Patients were classified on the basis of MRI findings for the CNS as having either hypothalamic lesions or complex syndromic phenotypes without structural lesions of the hypothalamus. Results In total, 63 consecutive children (42 girls and 21 boys) with non-isolated CPP were identified. Diverse diseases were detected, and the hypothalamic lesions visible on MRI (n = 28, 45% of cases) included hamartomas (n = 17; either isolated or with an associated syndromic phenotype), optic gliomas (n = 8; with or without neurofibromatosis type 1), malformations (n = 3) with interhypothalamic adhesions (n = 2; isolated or associated with syndromic CNS midline abnormalities, such as optic nerve hypoplasia, ectopic posterior pituitary) or arachnoid cysts (n = 1). The patients with non-structural hypothalamic lesions (n = 35, 55% of cases) had narcolepsy (n = 9), RASopathies (n = 4), encephalopathy or autism spectrum disorders with or without chromosomal abnormalities (n = 15) and other complex syndromic disorders (n = 7). Conclusion Our findings suggest that a large proportion (55%) of patients with non-isolated probable non-idiopathic CPP may have complex disorders without structural hypothalamic lesions on MRI. Future studies should explore the pathophysiological relevance of the mechanisms underlying CPP in these disorders.

Download Full-text

Prevalence and clinical characteristics of isolated forms of central precocious puberty: a cohort study at a single academic center

Acta Endocrinologica ◽

10.1530/eje-20-0862 ◽

2021 ◽

Vol 184 (2) ◽

pp. 243-251

Author(s):

Carole Harbulot ◽

Soucounda Lessim ◽

Dominique Simon ◽

Laetitia Martinerie ◽

Caroline Storey ◽

...

Keyword(s):

Cohort Study ◽

Precocious Puberty ◽

Clinical Characteristics ◽

Care Center ◽

Central Precocious Puberty ◽

Dominant Mode ◽

Pediatric Care ◽

Academic Center ◽

Observational Cohort ◽

Design And Methods

Objective Isolated central precocious puberty (CPP) includes sporadic, familial and adoption-related forms, and the characterization of its etiology is challenging. This study investigated the prevalence and clinical characteristics of isolated CPP. Design and methods This observational cohort study included all patients (n = 395) with CPP included in the database of a single academic pediatric care center over a period of 11.5 years. Results In total, 332 of the 395 patients (84%) had isolated forms of CPP; the proportion of male patients was lower in this group than for non-isolated CPP (4 vs 33%, P < 0.0001). These patients had sporadic (n = 228, 68.5%), familial (n = 82, 25%) or adoption-related (n = 22, 6.5%) forms. Clinical characteristics at diagnosis were similar between groups, but girls with sporadic CPP were older at referral than those with familial or adoption-related CPP (P < 0.02), and birth weight SDS was lower in adopted patients than in those from the sporadic and familial groups (P < 0.01). In the 72 families containing patients with familial forms, both recessive and dominant transmissions were observed between first-degree relatives. Potential maternal or paternal transmission was identified in two-thirds of the studied families, in similar proportions. An autosomal dominant mode of transmission with low penetrance was suggested by the high proportion of affected parents (33 of the 72 families, 46%). Clinical presentation was similar whatever the mode of inheritance. Conclusion These findings highlight the need for careful monitoring of the various forms of CPP. Future studies should explore pathophysiological mechanisms, particularly for familial forms.

Download Full-text

Prevalence of cranial MRI findings in girls with central precocious puberty: a systematic review and meta-analysis

Yearbook of Paediatric Endocrinology ◽

10.1530/ey.16.7.12 ◽

2019 ◽

Author(s):

Cantas-Orsdemir S ◽

Garb JL ◽

Allen HF

Keyword(s):

Systematic Review ◽

Precocious Puberty ◽

Meta Analysis ◽

Central Precocious Puberty ◽

Mri Findings ◽

Cranial Mri

Download Full-text

Early differences in auditory processing relate to Autism Spectrum Disorder traits in infants with Neurofibromatosis Type I

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-021-09364-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Jannath Begum-Ali ◽

◽

Anna Kolesnik-Taylor ◽

Isabel Quiroz ◽

Luke Mason ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Auditory Processing ◽

Neurofibromatosis Type ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Type I ◽

Sensory Reactivity ◽

Auditory Responses ◽

Repetition Suppression ◽

Age Related

Abstract Background Sensory modulation difficulties are common in children with conditions such as Autism Spectrum Disorder (ASD) and could contribute to other social and non-social symptoms. Positing a causal role for sensory processing differences requires observing atypical sensory reactivity prior to the emergence of other symptoms, which can be achieved through prospective studies. Methods In this longitudinal study, we examined auditory repetition suppression and change detection at 5 and 10 months in infants with and without Neurofibromatosis Type 1 (NF1), a condition associated with higher likelihood of developing ASD. Results In typically developing infants, suppression to vowel repetition and enhanced responses to vowel/pitch change decreased with age over posterior regions, becoming more frontally specific; age-related change was diminished in the NF1 group. Whilst both groups detected changes in vowel and pitch, the NF1 group were largely slower to show a differentiated neural response. Auditory responses did not relate to later language, but were related to later ASD traits. Conclusions These findings represent the first demonstration of atypical brain responses to sounds in infants with NF1 and suggest they may relate to the likelihood of later ASD.

Download Full-text

Vocal Fold Injection Augmentation for Post-Airway Reconstruction Dysphonia: A Case Series

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894211012594 ◽

2021 ◽

pp. 000348942110125

Author(s):

Mathieu Bergeron ◽

John Paul Giliberto ◽

Meredith E. Tabangin ◽

Alessandro de Alarcon

Keyword(s):

Vocal Fold ◽

Care Center ◽

Case Series ◽

Retrospective Chart Review ◽

Pediatric Care ◽

Voice Perception ◽

Perceptual Evaluation ◽

Airway Reconstruction ◽

Vocal Fold Injection ◽

History Of

Objectives: Post airway reconstruction dysphonia (PARD) is common and has a significant effect on the quality of life of patients. Vocal fold injection augmentation (VFIA) is one treatment that can be used to improve glottic insufficiency in some patients. The goal of this study was to characterize the use and outcomes of VFIA for PARD. Methods: Retrospective chart review from January 2007 to July 2018 at a tertiary pediatric care center. Consecutive patients with PARD who underwent VFIA, who had a preoperative voice evaluation and a follow-up evaluation within 3 months after VFIA (fat, carboxymethylcellulose gel, hyaluronic acid). Results: Thirty-four patients (20 female) underwent VFIA. The mean age at the time of the injection was 13.6 years (SD 6.1). Twenty patients (58.8%) had a history of prematurity and a mean of 1.8 open airway surgeries. After injection, 29/34 patients (85.3%) noted a subjective voice improvement. The baseline Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) overall severity score decreased by a mean of 5.7 (SD = 19.6) points, P = .12. Total pediatric Voice Handicap Index (pVHI) improved by 6.0 (SD = 19.5) points, from 57.4 (SD = 20.0) to 51.4 (SD = 17.2), P = .09. Functional pVHI subscore demonstrated a significant improvement, with a decrease of 3.4 (SD = 7.3) points, P = .02. All procedures were performed as an overnight observation and no complication occurred. Conclusion: Patients with PARD represent a complex subset of patients. VFIA is a straightforward intervention that may improve voice perception. Many patients reported subjective improvement despite minimal objective measurement. Further work is warranted to elucidate the role of injection in management of PARD

Download Full-text

Central precocious puberty in a girl with LEGIUS syndrome: an accidental association?

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01004-9 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Valentina Orlandi ◽

Paolo Cavarzere ◽

Laura Palma ◽

Rossella Gaudino ◽

Franco Antoniazzi

Keyword(s):

Genetic Analysis ◽

Precocious Puberty ◽

Central Precocious Puberty ◽

Neurofibromatosis Type ◽

Case Presentation ◽

New Variant ◽

Legius Syndrome ◽

Timing Of Puberty ◽

First Time

Abstract Background Central precocious puberty is a condition characterized by precocious activation of the hypothalamic-pituitary-gonadal axis. It may be idiopathic or secondary to organic causes, including syndromes such as Neurofibromatosis type 1 (NF1). Case presentation We presented a girl of 6 years and 10 months with almost 11 café-au-lait skin macules, without other clinical or radiological signs typical of NF1, and with a central precocious puberty. Genetic analysis evidenced the new variant NM-152594.2:c.304delAp. (Thr102Argfs*19) in SPRED1 gene, which allowed to diagnose Legius syndrome. Conclusions We report for the first time a case of central precocious puberty in a girl with Legius syndrome. The presence of central precocious puberty in a child with characteristic café-au-lait macules should suggest pediatricians to perform genetic analysis in order to reach a definitive diagnosis. Further studies on timing of puberty in patients with RASopathies are needed to better elucidate if this clinical association is casual or secondary to their clinical condition.

Download Full-text

Actionable and incidental neuroradiological findings in twins with neurodevelopmental disorders

Scientific Reports ◽

10.1038/s41598-020-79959-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Lynnea Myers ◽

Mai-Lan Ho ◽

Elodie Cauvet ◽

Karl Lundin ◽

Torkel Carlsson ◽

...

Keyword(s):

Neurodevelopmental Disorders ◽

Copy Number Variants ◽

Cross Sectional Study ◽

Autism Spectrum ◽

Molecular Signaling ◽

Mri Findings ◽

Cross Sectional ◽

Increased Risk ◽

Magnetic Resonance Imaging Mri ◽

Morphological Variants

AbstractWhile previous research has investigated neuroradiological findings in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), the entire range of neurodevelopmental disorders (NDDs) has not yet been well-studied using magnetic resonance imaging (MRI). Considering the overlap among NDDs and simultaneous development of the brain and face, guided by molecular signaling, we examined the relationship of actionable and incidental (non-actionable) MRI findings and NDD diagnoses together with facial morphological variants and genetic copy number variants (CNVs). A cross-sectional study was conducted with a twin cohort 8–36 years of age (57% monozygotic, 40% dizygotic), including 372 subjects (46% with NDDs; 47% female) imaged by MRI, 280 with data for facial morphological variants, and 183 for CNVs. Fifty-one percent of participants had MRI findings. Males had a statistically significantly higher percentage of MRI findings (57.7%) compared with females (43.8%, p = 0.03). Twin zygosity was not statistically significantly correlated with incidence or severity of specific MRI findings. No statistically significant association was found between MRI findings and any NDD diagnosis or facial morphological variants; however, MRI findings were statistically significantly associated with the number of CNVs (OR 1.20, 95% CI 1.00–1.44, p = 0.05, adjusted OR for sex 1.24, 95% CI 1.03–1.50, p = 0.02). When combining the presence of MRI findings, facial morphological variants, and CNVs, statistically significant relationships were found with ASD and ADHD diagnoses (p = 0.0006 and p = 0.002, respectively). The results of this study demonstrate that the ability to identify NDDs from combined radiology, morphology, and CNV assessments may be possible. Additionally, twins do not appear to be at increased risk for neuroradiological variants.

Download Full-text

Neurofibromatosis Type 1 and Autism Spectrum Disorder

PEDIATRICS ◽

10.1542/peds.2013-1868 ◽

2013 ◽

Vol 132 (6) ◽

pp. e1642-e1648 ◽

Cited By ~ 86

Author(s):

S. Garg ◽

J. Green ◽

K. Leadbitter ◽

R. Emsley ◽

A. Lehtonen ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Neurofibromatosis Type 1 ◽

Neurofibromatosis Type ◽

Autism Spectrum ◽

Spectrum Disorder

Download Full-text

Central precocious puberty due to hypothalamic hamartoma in neurofibromatosis type 1

HORMONES ◽

10.1007/bf03401416 ◽

2016 ◽

Vol 15 (1) ◽

pp. 144-146 ◽

Cited By ~ 1

Author(s):

Emanuele Bartolini ◽

Stefano Stagi ◽

Perla Scalini ◽

Andrea Bianchi ◽

Antonio Ciccarone ◽

...

Keyword(s):

Precocious Puberty ◽

Neurofibromatosis Type 1 ◽

Central Precocious Puberty ◽

Neurofibromatosis Type ◽

Hypothalamic Hamartoma

Download Full-text

Prevalence and course of thyroid dysfunction in neonates at high risk of Graves’ disease or with non-autoimmune hyperthyroidism

Acta Endocrinologica ◽

10.1530/eje-20-1320 ◽

2021 ◽

Vol 184 (3) ◽

pp. 431-440

Author(s):

Hassina Benlarbi ◽

Dominique Simon ◽

Jonathan Rosenblatt ◽

Cecile Dumaine ◽

Nicolas de Roux ◽

...

Keyword(s):

High Risk ◽

Thyroid Function ◽

Thyroid Dysfunction ◽

Genetic Disorder ◽

Care Center ◽

Receptor Gene ◽

High Serum ◽

Pediatric Care ◽

Graves Disease ◽

Neonatal Hyperthyroidism

Objective Neonatal hyperthyroidism may be caused by a permanent non-autoimmune genetic disorder or, more frequently, by maternally transmitted high serum TRAb levels. Variable thyroid dysfunction may be observed in this second context. We aimed to evaluate the prevalence of neonatal non-autoimmune hyperthyroidism and of the different types of thyroid function in neonates with a high risk of hyperthyroidism due to maternal Graves’ disease (GD). Design and methods This observational cohort study included all neonates identified in the database of a single academic pediatric care center, over a period of 13 years, as having non-autoimmune hyperthyroidism or an autoimmune disorder with high TRAb levels (above 6 IU/L) transmitted by their mothers. Patients were classified as having neonatal hyperthyroidism, hypothyroidism, or euthyroidism with a permanent or transient disorder. Results Two of the 34 consecutive neonates selected (6%) had permanent non-autoimmune hyperthyroidism due to germline (n = 1) or somatic (n = 1) mutations of the TSH receptor gene. The patients with high serum TRAb levels at birth had transient hyperthyroidism (n = 23), hypothyroidism (primary n = 2, central n = 3) or persistent euthyroidism (n = 4). Conclusion These original findings highlight the need for careful and appropriate monitoring of thyroid function in the long term, not only for the rare patients with non-autoimmune neonatal hyperthyroidism, but also for repeat monitoring during the first month of life in neonates with maternally transmitted high TRAb levels, to ensure the early identification of thyrotoxicosis in more than two thirds of cases and to detect primary or central hypothyroidism, thereby potentially decreasing associated morbidity.

Download Full-text