scholarly journals OR15-04 Central Precocious Puberty without Central Nervous System Lesions: Is It Really Idiopathic?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ana Pinheiro-Machado Canton ◽  
Vinicius Nahime Brito ◽  
Luciana Ribeiro Montenegro ◽  
Delanie Bulcão Macedo ◽  
Danielle de Souza Bessa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Genetic Analysis ◽  
Precocious Puberty ◽  
Uniparental Disomy ◽  
Central Precocious Puberty ◽  
Genetic Defects ◽  
Etiological Diagnosis ◽  
Genetic Causes ◽  
Cns Lesions

Abstract Background: The etiological diagnosis of central precocious puberty (CPP) has been classically divided into causes with or without central nervous system (CNS) lesions. Among the cases without CNS lesions, most of them are classified as idiopathic. In clinical practice, about 90% of girls and 40% of boys with CPP are considered having the idiopathic form. In the last two decades, pioneering studies have revealed underlying genetic causes in patients with apparently idiopathic CPP. Objective: To describe the frequency of genetic causes identified in a large cohort of patients with CPP followed in a single research center and to evaluate its role in the distribution of the etiology of CPP. Patients and methods: A retrospective evaluation was performed analyzing the etiological diagnosis of 276 patients (246 girls, 30 boys) with CPP followed in a single university hospital outpatient clinic from 2006 to 2019. The great majority (230 patients) presented without CNS lesions, being classified as idiopathic CPP group. Among the idiopathic CPP group, 170 of them had DNA samples available and were included for genetic analysis. Patients included for genetic analysis were systematically investigated for genetic causes of CPP using standard methodologies of genetic-molecular analysis. Briefly, they were studied as follows: 120 by Sanger sequencing; 18 by target panel sequencing; 27 by whole-exome sequencing; 5 by whole-genome sequencing; 113 by specific DNA methylation analysis; and 38 by genomic microarray. Results: Among the 276 patients with CPP, 46 (16.7%) had pathological CNS lesions: 19 boys and 27 girls, indicating the prevalence of CPP with CNS lesions (organic) of 63.3% in boys and 11% in girls. The most common cause of organic CPP was hypothalamic hamartoma (20 cases). Meanwhile 230 patients (83.3%) encompassed the apparently idiopathic CPP group. Main characteristics of this idiopathic CPP group were: 219 girls and 11 boys; 158 sporadic (69%), 68 familial (29.5%) and 4 adopted (1.5%). In the subset of patients with DNA available (162 girls, 8 boys), the frequency of genetic causes was 11.8% (20 cases: 18 girls and 2 boys). Analyzing by sex, the frequency of genetic causes was higher in boys (25%) than in girls (11.1%). The identified genetic defects were the following: 9 cases with inactivating MKRN3 mutations (8 families), 6 cases with inactivating DLK1 mutations (2 families), 1 case with activating KISS1R mutation, 1 case with activating KISS1 mutation, 2 sporadic cases with maternal uniparental disomy of chromosome 14, and 1 sporadic case with epimutation at DLK1 locus. Conclusion: Pathogenic genetic defects were identified in 11.8% of patients with apparently idiopathic CPP involving four distinct genes. Altogether, these genetic findings indicate a context of changing in the distribution of the etiological diagnosis of CPP in both sexes, highlighting the genetic causes.

Central Precocious Puberty in Girls: An Evidence-Based Diagnosis Tree to Predict Central Nervous System Abnormalities

PEDIATRICS ◽  
2002 ◽  
Vol 109 (1) ◽  
pp. 61-67 ◽  
Author(s):  
M. Chalumeau ◽  
W. Chemaitilly ◽  
C. Trivin ◽  
L. Adan ◽  
G. Breart ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Precocious Puberty ◽  
Central Precocious Puberty ◽  
Evidence Based

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

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.

scholarly journals Dying to Fall Asleep

2019 ◽  
pp. 724-742
Author(s):  
Jessica Vensel Rundo ◽  
Hillor Mehta ◽  
Reena Mehra
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Genetic Analysis ◽  
Genetic Disease ◽  
Prion Proteins ◽  
Amyloid Plaques ◽  
Definitive Diagnosis ◽  
Common Features ◽  
The Central Nervous System ◽  
Autonomic Hyperactivity

Fatal familial insomnia (FFI) is a rare autosomal dominant genetic disease characterized by progressive insomnia, autonomic hyperactivity, memory deficits, hallucinations, and myoclonus. Unlike its name, insomnia is not the most common initial presentation in patients with FFI. More common features like autonomic hyperactivity (hypertension and tachycardia) are often missed, delaying the diagnosis of FFI. Genetic analysis of FFI shows a D178N-129M mutation that results in generation of insoluble proteins (prion proteins) that aggregate to form amyloid plaques, leading to deterioration of the central nervous system, particularly in the hypothalamus. This case illustrates the difficulty in determining a definitive diagnosis in patients with FFI. Unfortunately, no treatment or cure is available for FFI. The disease is fatal in all the patients.

Spinal Reflexes in Ankle Flexor and Extensor Muscles After Chronic Central Nervous System Lesions and Functional Electrical Stimulation

2008 ◽  
Vol 23 (2) ◽  
pp. 133-142 ◽  
Author(s):  
Aiko K. Thompson ◽  
Kristen L. Estabrooks ◽  
SuLing Chong ◽  
Richard B. Stein
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nerve Stimulation ◽  
Reciprocal Inhibition ◽  
Spinal Reflexes ◽  
Foot Drop ◽  
Emg Activity ◽  
Muscle Nerve ◽  
Voluntary Contractions ◽  
Cns Lesions

Objective. Spinal reciprocal inhibitory and excitatory reflexes of ankle extensor and flexor muscles were investigated in ambulatory participants with chronic central nervous system (CNS) lesions causing foot drop as a function of time after lesion and stimulator use. Methods. Thirty-nine participants with progressive (eg, secondary progressive MS) and 36 with generally nonprogressive (eg, stroke) conditions were studied. The tibialis anterior (TA) and soleus maximum H-reflex/M-wave (Hmax/Mmax) ratios and maximum voluntary contractions (MVC) were measured and compared with those in age-matched control participants. Reciprocal inhibition was measured as a depression of the ongoing electromyographic (EMG) activity produced by antagonist muscle—nerve stimulation. Results. Participants with CNS lesions had significantly higher soleus Hmax/Mmax ratios than control participants, and reduced voluntary modulation of the reflexes occurred in both muscles. Reciprocal inhibition of soleus from common peroneal (CP) nerve stimulation was not significantly different from controls in either group. Inhibition of the TA by tibial nerve stimulation decreased and was eventually replaced by excitation in participants with nonprogressive disorders. No significant change occurred in progressive disorders. Use of a foot drop stimulator increased the TA, but not the soleus MVC overall. H-reflexes only showed small changes. Reciprocal inhibition of the TA increased considerably, while that of the soleus muscle decreased toward control values. Conclusions. Disorders that produce foot drop also produce reflex changes, some of which only develop over a period of years or even decades. Regular use of a foot drop stimulator strengthens voluntary pathways and changes some reflexes toward control values. Thus, stimulators may provide multiple benefits to people with foot drop.

DICER1-associated central nervous system sarcoma in children: comprehensive clinicopathologic and genetic analysis of a newly described rare tumor

2020 ◽  
Vol 33 (10) ◽  
pp. 1910-1921 ◽  
Author(s):  
Junne Kamihara ◽  
Vera Paulson ◽  
Micheál A. Breen ◽  
Theodore W. Laetsch ◽  
Dinesh Rakheja ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Genetic Analysis ◽  
Rare Tumor

Accuracy of Intraoperative Examination in Central Nervous System Lesions: A Study of 133 Cases

2019 ◽  
Vol 63 (3) ◽  
pp. 224-232
Author(s):  
Ludmila Barbosa de Souza Balsimelli ◽  
Jamille Costa de Oliveira ◽  
Flora Ávila Adorno ◽  
Clarissa Almeida Brites ◽  
Giuliano Stefanello Bublitz ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Frozen Section ◽  
Final Diagnosis ◽  
World Health ◽  
Histopathological Diagnosis ◽  
Low Grade ◽  
Predictive Values ◽  
Health Organization ◽  
Cns Lesions

Objective: Intraoperative examination is a highly valuable tool for the evaluation of central nervous system (CNS) lesions, helping the neurosurgeon to determine the best surgical management. This study aimed to evaluate the accuracy and to analyze the diagnostic disagreements and pitfalls of the intraoperative examinations through correlation with the final histopathological diagnosis in CNS lesions. Study Design: Retrospective analysis of intraoperative examination of CNS lesions and their final diagnosis obtained during 16 consecutive years. All diagnoses were reviewed and classified according to World Health Organization (WHO) grading for CNS tumors. Squash was performed in 119 cases, while frozen section and both methods were done in 7 cases each. Results: Among the 133 intraoperative examinations considered, 114 (85.7%) presented concordance and 19 (14.3%) diagnostic disagreement when compared with subsequent histopathological examinations. The sensitivity and specificity for the detection of neoplasia in intraoperative examination was 98 and 94%, respectively. The positive and negative predictive values were 99 and 88%, respectively. The accuracy for neoplastic and nonneoplastic disease was 85.7%. Disagreements were more frequent among low-grade (WHO grades I and II) neoplasms and nonmalignant cases. Conclusions: Our results showed good accuracy of the intraoperative assessments for diagnosis of CNS lesions, particularly in high-grade (grades III and IV) lesions and metastatic neoplasms.

Malformation of the Brain, Skull, and Spine

2021 ◽  
pp. 1057-1070
Author(s):  
Lily C. Wong-Kisiel
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Developmental Delay ◽  
Abnormal Development ◽  
Gene Expressions ◽  
Common Cause ◽  
Genetic Causes ◽  
The Central Nervous System ◽  
The Brain ◽  
Central Nervous System Malformation

Abnormal development of the central nervous system is a common cause of developmental delay and epilepsy. An understanding of central nervous system malformation begins with an overview of normal embryology. Genetic advances in embryogenesis have unfolded a complex orchestration of gene expressions in place of the traditional developmental epochs (induction, neurulation, proliferation, migration, organization, synaptogenesis, and myelination). Causes of malformation of the central nervous system are multifactorial. Genetic causes, vitamin excess or deficiency, infections, or teratogens any time during pregnancy may disturb the preprogrammed mechanisms.

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