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Elevated concentrations of T3 and T4 concomitant with nonsuppressed TSH are found in both TSH-producing tumors and resistance to thyroid hormone beta (RTHß), posing a diagnostic challenge. We demonstrate here a 54-year-old female who presented with palpitations, goiter, and elevated free T4 with nonsuppressed TSH concentrations (TSH 2.2 mIU/L [normal range, NR 0.27-4.2 mIU/L] and FT4 59.08 pmol/L [NR 12.0-22.0 pmol/L]). Because magnetic resonance imaging revealed a pituitary microadenoma (4 mm), she was diagnosed with TSH-secreting pituitary adenoma and underwent transsphenoidal surgery. Pathological reports showed no tumor cells. Subsequent genetic testing revealed a pathogenic variant in the THRB gene resulting in a His435Arg amino acid substitution in the T3 receptor isoform beta 1 (TRß1), suggestive of RTHß. In vitro and ex vivo studies revealed that the His435Arg mutated TRß1 (TRß1-H435R) completely abolishes the T3-induced transcriptional activation, nuclear receptor corepressor 1 release, steroid receptor coactivator 1 recruitment, and T3-induced thyroid hormone target gene expression, confirming the pathogenicity of this variant. The identification of a pituitary microadenoma in a patient with RTHß led to a misdiagnosis of a TSH-producing tumor and unnecessary surgery. Genetic testing proved pivotal for an accurate diagnosis, suggesting earlier consideration in similar clinical scenarios.
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OBJECTIVES: While global incidence rates (IR) of childhood diabetes are increasing, there is a notable lack of current information on the incidence of childhood-onset diabetes in Thailand. This study aims to illustrate the age-standardized IR and types of childhood diabetes using multicenter regional data in Northern Thailand from 2005 to 2022 and to assess the impact of the COVID-19 pandemic. METHODS: Data on newly diagnosed childhood diabetes were retrospectively collected between 2005 and 2016 and prospectively recorded for all incident cases between 2016 and 2022. The capture-recapture method was applied to estimate the completeness of ascertainment. The age-standardized IR of diabetes was calculated. The IR of diabetes and the prevalence/severity of DKA at onset were compared between the pre-pandemic and pandemic periods. RESULTS: Among 210 patients, type 1 diabetes (T1D) accounted for 56.2â¯%, type 2 diabetes (T2D) for 39â¯%, and other types for 4.8â¯%. The T1D age-standardized IR significantly increased from 0.30 in 2005 to 3.11/100,000 person/year in 2022, mirroring the T2D trend, which increased from 0.33 to 3.15/100,000 person/year. The average T1D age-standardized IR, including the prevalence/severity of DKA at diagnosis, did not significantly differ between the pre-pandemic and pandemic periods (2.11 vs. 2.36/100,000 person/year, p-value=0.67). However, the average T2D age-standardized IR significantly increased from 0.83 to 2.15/100,000 person/year during the pandemic (p-value=0.0057). CONCLUSIONS: This study highlights an increased incidence of childhood T1D and T2D in Northern Thailand over a two-decade period. Notably, during the COVID-19 pandemic, the T1D incidence remained stable, while a significant rise in T2D incidence was observed.
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COVID-19 , Diabetes Mellitus Tipo 1 , SARS-CoV-2 , Humanos , Tailândia/epidemiologia , COVID-19/epidemiologia , Criança , Masculino , Incidência , Feminino , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/diagnóstico , Adolescente , Pré-Escolar , Estudos Retrospectivos , Lactente , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Prevalência , Idade de Início , Pandemias , Índice de Gravidade de Doença , Recém-NascidoRESUMO
Pheochromocytomas are catecholamine-producing tumors derived from the adrenomedullary chromaffin cells. The presentation is a classic triad of episodic headaches, sweating, and tachycardia. Hypertensive crisis can occur due to profuse catecholamine excess. Unusual manifestations mimicking cardiogenic shock, arrhythmia, and myocarditis have been rarely reported in children. We present a case with uncommon manifestations of pheochromocytoma in a child, including the episodes of exercised-induced presyncope with QT prolongation, and subsequently cardiogenic shock due to fulminant myocarditis. He later developed hypertensive crisis. The adrenal mass on abdominal computed tomography with an increased chromogranin A level and elevated plasma normetanephrine, and the histological study confirmed the diagnosis of pheochromocytoma. Cardiac functions completely recovered after adrenalectomy. Genetic testing was positive for von Hippel-Lindau syndrome. We describe pheochromocytoma crisis presenting with prolonged QT and catecholamine-induced myocarditis. We discuss the clues to assist in the diagnosis of this condition and its appropriate treatment.
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INTRODUCTION: Inactivating mutations of the calcium-sensing receptor (CASR) gene result in neonatal severe hyperparathyroidism (NSHPT). Total parathyroidectomy is an effective way to control life-threatening hypercalcemia in NSHPT but leads to permanent hypoparathyroidism. An alternative surgical option is subtotal parathyroidectomy. However, few cases were reported in the literature. Here, we report two unrelated NSHPT patients, one with a novel homozygous mutation (c.1817T>C; p.Leu606Pro) in CASRand the other with heterozygous for the same mutation who also carried two rare intronic variants in CASR. The outcomes of subtotal parathyroidectomy in these patients are also described. CASE PRESENTATION: Two infants presented with an alteration of consciousness, respiratory distress, and bradycardia. Severe hypercalcemia, hypophosphatemia, and markedly elevated parathyroid hormone levels were identified, suggesting NSHPT. Cinacalcet was unable to control calcium (Ca) levels of both patients. A novel heterozygous and homozygous missense mutation c.1817T>C; p.Leu606Pro was identified in patients 1 and 2, respectively. Based on the model prediction, proline substitution at Leu606 is likely to disrupt conversion between the active and inactive conformations at the extracellular to transmembrane domain interface of CASR. In addition, two extremely rare intronic variants in CASR (chr3:g.122180314A>G and chr3:g.122251601G>A, based on GRCh38) were identified in patient 1 and his mother. These variants might have contributed to the clinical manifestations of patient 1 who was heterozygous for the c.1817T>C; p.Leu606Pro variant. Subtotal parathyroidectomy was performed by removing three and a half parathyroid glands. So far, patient 1 has been in normocalcemia for 5 years. Patient 2 was in normocalcemia for 16 months after surgery and subsequently developed mild hypoparathyroidism which required only low-dose calcitriol treatment. CONCLUSION: We report a novel heterozygous and homozygous missense variant (c.1817T>C; p.Leu606Pro) in CASR in two NSHPT patients. The mutation likely disrupts conformational changes of CASR and results in cinacalcet unresponsiveness. Intronic variants in CASR identified in the patient with heterozygous variant might have contributed to the clinical manifestations of the patient. Although total parathyroidectomy is widely accepted as a standard treatment for NSHPT, we demonstrate that subtotal parathyroidectomy is also an effective procedure to normalize Ca levels and allow these patients to be in normocalcemia or mild hypoparathyroidism, which is simply controlled by low-dose calcitriol treatment. Subtotal parathyroidectomy appeared to be an effective treatment for NSHPT regardless of the molecular etiologies.
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Hipercalcemia , Hiperparatireoidismo Primário , Hipoparatireoidismo , Recém-Nascido , Lactente , Humanos , Cinacalcete/uso terapêutico , Cálcio , Hipercalcemia/genética , Hipercalcemia/tratamento farmacológico , Receptores de Detecção de Cálcio/genética , Paratireoidectomia , Calcitriol , Hiperparatireoidismo Primário/genética , Mutação , Hipoparatireoidismo/genética , Hipoparatireoidismo/tratamento farmacológicoRESUMO
CONTEXT: Biallelic pathogenic variants in the NEUROG3 gene cause malabsorptive diarrhea, insulin-dependent diabetes mellitus (IDDM), and rarely hypogonadotropic hypogonadism. With only 17 reported cases, the clinical and mutational spectra of this disease are far from complete. OBJECTIVE: To identify the underlying genetic etiology in 3 unrelated Thai patients who presented with early-onset malabsorptive diarrhea, endocrine abnormalities, and renal defects and to determine the pathogenicity of the newly identified pathogenic variants using luciferase reporter assays and western blot. METHODS: Three unrelated patients with congenital diarrhea were recruited. Detailed clinical and endocrinological features were obtained. Exome sequencing was performed to identify mutations and in vitro functional experiments including luciferase reporter assay were studied to validate their pathogenicity. RESULTS: In addition to malabsorptive diarrhea due to enteric anendocrinosis, IDDM, short stature, and delayed puberty, our patients also exhibited pituitary gland hypoplasia with multiple pituitary hormone deficiencies (Patient 1, 2, 3) and proximal renal tubulopathy (Patient 2, 3) that have not previously reported. Exome sequencing revealed that Patient 1 was homozygous for c.371C > G (p.Thr124Arg) while the other 2 patients were homozygous for c.284G > C (p.Arg95Pro) in NEUROG3. Both variants have never been previously reported. Luciferase reporter assay demonstrated that these 2 variants impaired transcriptional activity of NEUROG3. CONCLUSIONS: This study reported pituitary gland hypoplasia with multiple pituitary hormone deficiencies and proximal renal tubulopathy and 2 newly identified NEUROG3 loss-of-function variants in the patients with NEUROG3-associated syndrome.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos , Diabetes Mellitus Tipo 1 , Humanos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Proteínas do Tecido Nervoso/genética , Mutação , Diarreia/genética , Diarreia/congênito , Fenótipo , Hormônios HipofisáriosRESUMO
OBJECTIVES: Primary congenital hypothyroidism (CH) is a preventable cause of mental retardation. Iatrogenic hyperthyroidism has occasionally been reported using the recommended LT4 dosage. Currently, information regarding iatrogenic hyperthyroidism and predictive factors for permanent hypothyroidism (P-CH) among Thai patients is lacking. The aim of this study is to determine the prevalence and factors for predicting iatrogenic hyperthyroidism at one month after LT4 initiation and for predicting P-CH in primary CH infants. METHODS: This retrospective cohort study involved 87 infants with primary CH. Patients were classified by thyroid status at one month after LT4 initiation. At 3 years, patients were reevaluated after LT4 cessation and assigned as P-CH or transient CH (T-CH). Differences between groups were analyzed. RESULTS: One month after LT4 initiation, 35.6% of patients were classified as having iatrogenic hyperthyroidism. An initial LT4 dose of 10.2 µg/kg/day (sensitivity 64.5%, specificity 71.4%) was a suitable cutoff value for predicting iatrogenic hyperthyroidism, wherein 55.6 and 21.6% of patients were treated with initial doses of ≥10.2 and <10.2 µg/kg/day, respectively (p=0.004). Initial LT4 dose was the only predictive factor for thyroid status after initial treatment. At reevaluation, 47.4% of patients were diagnosed with P-CH. LT4 dosage at 3 years of age was significantly higher in patients with P-CH (3.3 vs. 2.85 µg/kg/day, p=0.02) and the only relevant factor for predicting P-CH. CONCLUSIONS: Iatrogenic hyperthyroidism is common among infants with primary CH when treated with the recommended LT4 dosage. LT4 dose was the only factor for predicting iatrogenic hyperthyroidism after LT4 initiation and the diagnosis of P-CH.
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Hipotireoidismo Congênito , Hipertireoidismo , Tireotoxicose , Hipotireoidismo Congênito/diagnóstico , Hipotireoidismo Congênito/epidemiologia , Hipotireoidismo Congênito/etiologia , Humanos , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/epidemiologia , Hipertireoidismo/etiologia , Doença Iatrogênica/epidemiologia , Lactente , Prevalência , Estudos Retrospectivos , Tireotoxicose/tratamento farmacológico , Tireotropina , TiroxinaRESUMO
North-Eastern Brazil saw intensive application of the insecticide pyriproxyfen (PPF) during the microcephaly outbreak caused by the Zika virus (ZIKV). ZIKV requires the neural RNA-binding protein Musashi-1 to replicate. Thyroid hormone (TH) represses MSI1. PPF is a suspected TH disruptor. We hypothesized that co-exposure to the main metabolite of PPF, 4'-OH-PPF, could exacerbate ZIKV effects through increased MSI1 expression. Exposing an in vivo reporter model, Xenopus laevis, to 4'-OH-PPF decreased TH signaling and increased msi1 mRNA and protein, confirming TH-antagonistic properties. Next, we investigated the metabolite's effects on mouse subventricular zone-derived neural stem cells (NSCs). Exposure to 4'-OH-PPF dose-dependently reduced neuroprogenitor proliferation and dysregulated genes implicated in neurogliogenesis. The highest dose induced Msi1 mRNA and protein, increasing cell apoptosis and the ratio of neurons to glial cells. Given these effects of the metabolite alone, we considered if combined infection with ZIKV worsened neurogenic events. Only at the fourth and last day of incubation did co-exposure of 4'-OH-PPF and ZIKV decrease viral replication, but viral RNA copies stayed within the same order of magnitude. Intracellular RNA content of NSCs was decreased in the combined presence of 4'-OH-PPF and ZIKV, suggesting a synergistic block of transcriptional machinery. Seven out of 12 tested key genes in TH signaling and neuroglial commitment were dysregulated by co-exposure, of which four were unaltered when exposed to 4'-OH-PPF alone. We conclude that 4'-OH-PPF is an active TH-antagonist, altering NSC processes known to underlie correct cortical development. A combination of the TH-disrupting metabolite and ZIKV could aggravate the microcephaly phenotype.
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Células-Tronco Neurais , Infecção por Zika virus , Zika virus , Animais , Camundongos , Piridinas , Hormônios TireóideosRESUMO
Background The standard treatment of central precocious puberty (CPP) is gonadotropin-releasing hormone analogues (GnRHa). It is a concern that children treated with GnRHa are at risk of developing obesity which could impair the treatment outcomes. This study aimed to investigate the effect of GnRHa on body mass index (BMI) standard deviation score (SDS), and the influence of BMI status on treatment outcomes in children with idiopathic CPP (iCPP). Methods A retrospective cohort study in children with iCPP who completed GnRHa treatment and had attained near final adult height (NFAH) was conducted. Children with a history of disease or drug ingestion which could affect their BMI were excluded. BMI, BMI SDS, height (Ht), Ht SDS, predicted adult height (PAH), and NFAH were compared at baseline, 1 and 2 years during treatment, and at NFAH according to the baseline BMI status; normal weight and overweight/obesity. Results Fifty-eight children with iCPP treated with GnRHa were enrolled. The BMI SDS was significantly increased at 1 and 2 years during treatment in the overweight/obese group and at 1 year during treatment in the normal-weight group. However, at NFAH (2 years after treatment discontinuation), the BMI SDS was not statistically different from baseline in both groups. Ht gain, change in Ht SDS and BMI SDS were not statistically different from the baseline in both groups. Conclusions GnRHa results in a transient increase in BMI SDS during treatment and returned to baseline after treatment cessation. The benefit of GnRHa treatment on final Ht improvement is similar between overweight/obese and normal-weight patients.
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Estatura , Peso Corporal , Hormônio Liberador de Gonadotropina/administração & dosagem , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Puberdade Precoce/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Criança , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Masculino , Prevalência , Puberdade Precoce/epidemiologia , Puberdade Precoce/patologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background: Thyroid hormone (TH) acts on TH receptors (TRs) and regulates gene transcription by binding of TRs to TH response elements (TREs) in target gene promoters. The transcriptional activity of TRs is modulated by interactions with TR-coregulatory proteins. Mutations in TRα cause resistance to thyroid hormone alpha (RTHα). In this study, we analyzed if, beyond reduced triiodothyronine (T3) affinity, altered interactions with cofactors or different TREs could account for the differential impaired transcriptional activity of different mutants. Methods: We evaluated four mutants derived from patients (D211G, M256T, A263S, and R384H) and three artificial mutants at equivalent positions in patients with RTHß (T223A, L287V, and P398H). The in vitro transcriptional activity was evaluated on TRE-luciferase reporters (DR4, IR0, and ER6). The affinity for T3 and interaction with coregulatory proteins (nuclear receptor corepressor 1 [NCoR1] and steroid receptor coactivator 1 [SRC1]) were also determined. Results: We found that the affinity for T3 was significantly reduced for all mutants, except for TRα1-T223A. The reduction in the T3 sensitivity of the transcriptional activity on three TREs, the dissociation of the corepressor NCoR1, and the association of the coactivator SRC1 recruitment for each mutant correlated with the reduced affinity for T3. We did not observe mutation-specific alterations in interactions with cofactors or TREs. Conclusions: In summary, the degree of impaired transcriptional activity of mutants is mainly determined by their reduced affinity for T3.
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Mutação/genética , Receptores alfa dos Hormônios Tireóideos/genética , Receptores alfa dos Hormônios Tireóideos/metabolismo , Linhagem Celular Tumoral , Simulação por Computador , Humanos , Ligantes , Modelos Moleculares , Correpressor 1 de Receptor Nuclear/genética , Coativador 1 de Receptor Nuclear/genética , Ligação Proteica , Elementos de Resposta , Transcrição Gênica , Tri-Iodotironina/metabolismoRESUMO
CONTEXT: The two major forms of circulating thyroid hormones (THs) are T3 and T4. T3 is regarded as the biologically active hormone because it binds to TH receptors (TRs) with greater affinity than T4. However, it is currently unclear what structural mechanisms underlie this difference in affinity. OBJECTIVE: Prompted by the identification of a novel M256T mutation in a resistance to TH (RTH)α patient, we investigated Met256 in TRα1 and the corresponding residue (Met310) in TRß1, residues previously predicted by crystallographic studies in discrimination of T3 vs T4. METHODS: Clinical characterization of the RTHα patient and molecular studies (in silico protein modeling, radioligand binding, transactivation, and receptor-cofactor studies) were performed. RESULTS: Structural modeling of the TRα1-M256T mutant showed that distortion of the hydrophobic niche to accommodate the outer ring of ligand was more pronounced for T3 than T4, suggesting that this substitution has little impact on the affinity for T4. In agreement with the model, TRα1-M256T selectively reduced the affinity for T3. Also, unlike other naturally occurring TRα mutations, TRα1-M256T had a differential impact on T3- vs T4-dependent transcriptional activation. TRα1-M256A and TRß1-M310T mutants exhibited similar discordance for T3 vs T4. CONCLUSIONS: Met256-TRα1/Met310-TRß1 strongly potentiates the affinity of TRs for T3, thereby largely determining that T3 is the bioactive hormone rather than T4. These observations provide insight into the molecular basis for underlying the different affinity of TRs for T3 vs T4, delineating a fundamental principle of TH signaling.
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Receptores alfa dos Hormônios Tireóideos/genética , Receptores beta dos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/genética , Tiroxina/genética , Tri-Iodotironina/genética , Feminino , Humanos , Mutação , Ativação Transcricional/genéticaRESUMO
Leucine 341 has been predicted from crystal structure as an important residue for thyroid hormone receptor beta (TRß) function, but this has never been confirmed in functional studies. Here, a novel p.L341V mutation as a cause of resistance to TRß is described, suggesting an important role for L341 in TRß function. In silico and in vitro studies confirmed that substituting L341 with valine and other non-polar amino acids impairs sensitivity of TRß for triiodothyronine to various degrees, depending on their side-chain size and orientation.
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BACKGROUND: Vitamin D deficiency is common in patients with thalassemia. Vitamin D deficiency could be related to cardiac dysfunction. Increased parathyroid hormone (PTH) is also known to be associated with heart failure. OBJECTIVES: To determine the prevalence of Vitamin D deficiency and to explore the impact of Vitamin D deficiency on cardiac iron and function in patients with transfusion-dependent thalassemia. METHOD: A cross-sectional study in patients with Transfusion-dependent thalassemia was conducted. Patients with liver disease, renal disease, type 1 diabetes, malabsorption, hypercortisolism, malignancy, and contraindication for MRI were excluded. Calcium, phosphate, PTH, vitamin D-25OH were measured. CardiacT2* and liver iron concentration (LIC) and left ventricular ejection fraction (LVEF) were determined. Results Sixty-one (33M/28F) patients with Transfusion-dependent thalassemia were enrolled. The prevalence of Vitamin D deficiency was 50.8%. Patients with cardiac siderosis had tendency for lower D-25OH than those without siderosis (15.9 (11.7-20.0) vs. 20.2 (15.85-22.3) ng/mL); p = 0.06). Serum calcium, phosphate, PTH, LIC, cardiac T2*, and LVEF were not different between the groups with or without Vitamin D deficiency. Patients with Vitamin D deficiency had significantly lower hemoglobin levels compared to those without Vitamin D deficiency (7.5 (6.93-8.33) vs. 8.1 (7.30-8.50) g/dL; p = 0.04). The median hemoglobin in the last 12 months was significantly correlated with D-25OH. Cardiac T2* had significant correlation with PTH. CONCLUSION: Vitamin D deficiency is prevalent in patients with Transfusion-dependent thalassemia. Vitamin D level is correlated with hemoglobin level. Vitamin D status should be routinely assessed in these patients. Low PTH is correlated with increased cardiac iron. This study did not demonstrate an association between Vitamin D deficiency and cardiac iron or function in patients with Transfusion-dependent thalassemia.
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Transfusão de Sangue , Cardiopatias , Ferro/metabolismo , Miocárdio/metabolismo , Deficiência de Vitamina D , Adolescente , Adulto , Criança , Estudos Transversais , Feminino , Cardiopatias/epidemiologia , Cardiopatias/etiologia , Cardiopatias/metabolismo , Humanos , Masculino , Prevalência , Talassemia/epidemiologia , Talassemia/metabolismo , Talassemia/terapia , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/etiologia , Deficiência de Vitamina D/metabolismoRESUMO
BACKGROUND: Imatinib mesylate (IM) is a selective tyrosine kinase inhibitor and is approved for indefinite treatment of pediatric chronic myelogenous leukemia (CML). Potential side-effects regarding growth failure and bone metabolism have been reported but data are still scarce in pediatric CML. METHODS: Six chronic-phase CML children on IM treatment with a median age of 9.87 years (range, 5.33-12.67 years) were enrolled in the study. Growth, bone mineral density (BMD), bone parameters, 25(OH)-vitamin D3 (25-OHD3) and blood tests including parathyroid hormone, insulin-like growth factor-1 (IGF-1), IGF binding protein 3, thyroid function test and sex hormones were assessed. RESULTS: Median duration of IM treatment was 78.5 months. Height velocity was suppressed during the first 30 months of treatment and improved gradually afterwards. Two patients (33.3%) had decreased lumbar spine BMD z-scores (<1.5 SD). Patients with decreased BMD had higher mean IM exposure time than those with normal BMD. The majority of patients (n = 5) had low 25-OHD3 (<30 ng/mL), but there was no correlation between BMD and 25-OHD3 status. Other blood tests were normal. CONCLUSIONS: This study supports and confirms the need for monitoring the side-effects of IM treatment on growth, bone density and vitamin D status in pediatric CML. Prolonged IM treatment was associated with low BMD without disturbing bone parameters. There was high prevalence of vitamin D insufficiency. Therefore, the beneficial effect of vitamin D supplement should be explored with regard to the effects on height velocity and BMD in CML patients with vitamin D insufficiency.
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Antineoplásicos/efeitos adversos , Mesilato de Imatinib/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adolescente , Antineoplásicos/uso terapêutico , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Seguimentos , Humanos , Mesilato de Imatinib/uso terapêutico , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Sotos syndrome is a common genetic overgrowth syndrome caused by a mutation of the NSD1 gene, which is located at chromosome 5q35 and normally encodes a histone methyltransferase protein. The general characteristics of this syndrome include a characteristic facial appearance, developmental delay, and overgrowth, resulting in macrocephaly and tall stature. We describe rhabdomyolysis and hypocalcemia due to hypoparathyroidism in a 3-year-old Korean boy with Sotos syndrome. He was diagnosed with Sotos syndrome based on the typical phenotype and has a heterozygous nonsense mutation (c.4710C>A [p.Cys1570*]) of the NSD1 gene, which causes a premature stop codon and a truncating protein mutation. Hypoparathyroidism has never been described in Sotos syndrome. This report may therefore expand the phenotypic spectrum of this syndrome.