Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026827 (hypotonia)
 5,860 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MCT8 is a cellular transporter of thyroid hormones important in their action and metabolization. We report a male patient with the novel inactivating mutation 630insG in the coding region in exon 1 of MCT8. He was characterized clinically by severe neurologic impairment (initially with global hypotonia, later evolving with generalized hypertonia), normal growth during infancy, reduced weight gain, and absence of typical signs and symptoms of hypothyroidism, while the laboratory evaluation disclosed elevated T3, low total and free T4, and mildly elevated TSH serum levels. Treatment with levothyroxine improved thyroid hormone profile but was not able to alter the clinical picture of the patient. These data reinforce the concept that the role of MCT8 is tissue-dependent: while neurons are highly dependent on MCT8, bone tissue, adipose tissue, muscle, and liver are less dependent on MCT8 and, therefore, may suffer the consequences of the exposition to high serum T3 levels.
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PMID:Novel mutation in MCT8 gene in a Brazilian boy with thyroid hormone resistance and severe neurologic abnormalities. 2146 14

We report prolonged desaturation in a child with Down syndrome (DS) and atrial septal defect due to undiagnosed interstitial lung disease. An 18-month-old child with DS was scheduled for bilateral lens aspiration for cataract. The child had atrial septal defect and hypothyroidism. He also had delayed milestones and hypotonia with episodes of recurrent respiratory tract infection necessitating repeated hospitalization. Preoperative evaluation was unremarkable. General anaesthesia and controlled ventilation using proseal laryngeal mask airway was instituted. He had uneventful intraoperative period. In the postoperative period, the child had desaturation 1 hour after surgery on discontinuation of oxygen supplementation by face mask, which improved with oxygen therapy. Supplemental oxygen via face mask was continued and weaned off over several days. On further evaluation, the child was diagnosed as having interstitial lung disease. He improved and discharged from the hospital 15 days after the surgery with room air saturation of 90%.
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PMID:Prolonged postoperative desaturation in a child with Down syndrome and atrial septal defect. 2222 7

13q deletion syndrome is caused by the absence of a portion of the long arm of chromosome 13. This syndrome is a rare condition characterized by a wide range of clinical findings. Phenotype varies with the location and size of the deletion. We report a female dizygotic twin with a proximal deletion of 13q and failure to thrive, hypotonia, and multiple anomalies included pytosis and total ophthalmology at right side, strabismus at left, bilateral iris heterochromia and telecantus. She had a broad nasal bridge with flat philtrum, micrognathia and antevert ear lobes. Her umbilicus had vanished. Her left coxa was dislocated and left toes were overlapped. She was also found to have hypertriglyceridemia, hypercholesterolemia, and hypothyroidism. Chromosome analysis showed a proximal deletion of chromosome 13 [karyotype 46,XX,del(13) (q14.2q31.3)] which was confirmed by high-resolution microarray based comparative genomic hybridization. The described patient is unique among similar rare cases with different deletion breakpoints. It is the first case of 13q14.2q31.3 deletion where the breakpoints are clearly defined, indicating the importance of detailed clinical description and high-resolution genomic analysis for characterization of rare genetic syndromes.
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PMID:A case of del(13)(q14.2)(q31.3) associated with hypothyroidism, hypertriglyceridemia, hypercholesterolemia and total ophthalmoplegia. 2238 6

The monosomy 1p36 syndrome is a cause of syndromic obesity. It is characterised by psychomotor delay, hypotonia and typical craniofacial dysmorphism. Other features commonly associated are behavioural anomalies including hyperphagia and self-injuring, seizures, congenital heart disease and hypothyroidism. The authors report the case of a 9-year and 5-month-boy referred to the paediatric endocrinology clinics for morbid obesity. Clinical findings were generalised obesity with a body mass index >95th centile, acanthosis nigricans of the neck, arms with self inflicted lesions, deep-set eyes, straight eyebrows, broad nasal bridge and pointed chin. He was unable to walk and had no expressive language. Cytogenetic analysis identified 1p36.33-pter deletion (~139 Mb terminal deletion in chromosome 1 short arm) and Y chromosome duplication. The blood analysis showed insulin resistance and dyslipidaemia. The authors emphasise the need to consider monosomy 1p36 as a cause of severe psychomotor delay and obesity.
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PMID:Morbid obesity in a child with monosomy 1p36 syndrome. 2260 91

Prader-Willi syndrome (PWS) is a complex multisystem genetic disorder characterized by hypothalamic-pituitary dysfunction. The main clinical features include neonatal hypotonia, distinctive facial features, overall developmental delay, and poor growth in infancy, followed by overeating with severe obesity, short stature, and hypogonadism later in development. This paper reviews recent updates regarding the genetic aspects of this disorder. Three mechanisms (paternal deletion, maternal disomy, and deficient imprinting) are recognized. Maternal disomy can arise because of 4 possible mechanisms: trisomy rescue (TR), gamete complementation (GC), monosomy rescue (MR), and postfertilization mitotic nondisjunction (Mit). Recently, TR/GC caused by nondisjunction at maternal meiosis 1 has been identified increasingly, as a result of advanced maternal childbearing age in Korea. We verified that the d3 allele increases the responsiveness of the growth hormone (GH) receptor to endogenous GH. This paper also provides an overview of endocrine dysfunctions in children with PWS, including GH deficiency, obesity, sexual development, hypothyroidism, and adrenal insufficiency, as well as the effects of GH treatment. GH treatment coupled with a strictly controlled diet during early childhood may help to reduce obesity, improve neurodevelopment, and increase muscle mass. A more active approach to correct these hormone deficiencies would benefit patients with PWS.
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PMID:Endocrine problems in children with Prader-Willi syndrome: special review on associated genetic aspects and early growth hormone treatment. 2284 16

Prader-Willi syndrome (PWS) is a complex genetic disorder, caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13. In infancy it is characterized by hypotonia with poor suck resulting in failure to thrive. As the child ages, other manifestations such as developmental delay, cognitive disability, and behavior problems become evident. Hypothalamic dysfunction has been implicated in many manifestations of this syndrome including hyperphagia, temperature instability, high pain threshold, sleep disordered breathing, and multiple endocrine abnormalities. These include growth hormone deficiency, central adrenal insufficiency, hypogonadism, hypothyroidism, and complications of obesity such as type 2 diabetes mellitus. This review summarizes the recent literature investigating optimal screening and treatment of endocrine abnormalities associated with PWS, and provides an update on nutrition and food-related behavioral intervention. The standard of care regarding growth hormone therapy and surveillance for potential side effects, the potential for central adrenal insufficiency, evaluation for and treatment of hypogonadism in males and females, and the prevalence and screening recommendations for hypothyroidism and diabetes are covered in detail. PWS is a genetic syndrome in which early diagnosis and careful attention to detail regarding all the potential endocrine and behavioral manifestations can lead to a significant improvement in health and developmental outcomes. Thus, the important role of the provider caring for the child with PWS cannot be overstated.
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PMID:Endocrine manifestations and management of Prader-Willi syndrome. 2396 41

Decreased level of consciousness in neonates may result from different etiologies, including rare metabolic and hormonal disorder due to anterior pituitary insufficiency. In this case report, a five-day-old newborn boy was referred to the neonatal intensive care unit of Mustafa Khomeini hospital of Ilam, Iran. He had an open anterior fontanel with no history of prenatal and familial diseases. Clinical examination showed decreased level of consciousness so that this patient responded only to painful stimuli. Furthermore, unconsciousness, hyperbilirubinemia, and hypotonia were fully evident. Given the clinical findings and decreased level of consciousness, hormonal diagnostic tests and brain CT scan were performed for any evidence of hypopituitarism. Clinical and experimental findings were consistent with the generalized edema and pituitary insufficiency secondary to central hypothyroidism and cortisol deficiency. Based on the findings, the neonate was put on the hormonal replacement therapy and, as the result, all of the abnormal clinical symptoms disappeared. In conclusion, fatal neonatal diseases may be mistaken with unimportant clinical findings at the first examination. Therefore, comprehensive attention to all potential causes of such symptoms in the neonates should be given for early diagnosis and treatment, and to prevent any fatal and irreversible complications.
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PMID:Hypopituitarism in a neonate with hyperbilirubinemia and decreased level of consciousness: a case report study. 2465 93

OSA is associated with significant adverse outcomes with far-reaching health-care implications. OSA is much more common and severe in patients with Down syndrome (DS) than in the general population, yet there is a striking lack of literature in this area. In this review article, we have summarized the current state of knowledge and presented the available data on OSA in DS. The higher prevalence and severity of OSA in patients with DS may be related to unique upper airway anatomic features as well as increased risk for obesity, hypothyroidism, gastroesophageal reflux disease, and generalized hypotonia. Although many of the manifestations of OSA in patients with DS are similar to those seen in the general population, the relative morbidity is significantly higher. For individuals with DS who already face cognitive challenges, the added impact of OSA on cognitive function may hinder their ability to function independently and reach their full potential. Screening and evaluation for OSA should be done in children and adults with DS. Treatment of OSA in DS involves the use of CPAP, upper airway surgery, and dental appliances, along with weight-reduction strategies, nasal steroids, and oral leukotriene modifiers as adjunctive treatments. The treatment plan should be individualized for each patient with DS, taking into account age, comorbid conditions, and barriers to treatment adherence. Future research should aim to better characterize OSA, further evaluate neurocognitive outcomes, and evaluate the efficacy of treatments in patients with DS.
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PMID:Sleep-disordered breathing in Down syndrome. 2564 10

The monocarboxylate transporter 8 (MCT8) gene, located on chromosome Xq13.2, encodes a thyroid hormone transporter that is involved in triiodothyronine (T3) uptake into central neurons. MCT8 mutations cause an X-linked syndromic disorder known as Allan-Herndon-Dudley syndrome (AHDS) that is characterized by severe psychomotor delays, abnormal thyroid function, and hypomyelinated leukodystrophies. We identified 2 AHDS patients with developmental delays, truncal hypotonia, and spastic paraplegia. These patients presented with psychomotor retardation and characteristic thyroid function abnormalities, such as elevated T3 and low T4 levels. Direct MCT8 sequencing identified heterozygous mutations in each patient: p.I114N and p.A224V, respectively. Because it is difficult to suspect AHDS solely according to neurological features, thyroid function, including the T3 level, should be screened in male patients with X-linked mental retardation. Although the clinical features of hypothyroidism cannot be improved by only administering levothyroxine treatment, early diagnosis, management, and appropriate genetic counseling should be provided to at-risk families.
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PMID:Clinical and endocrine features of two Allan-Herndon-Dudley syndrome patients with monocarboxylate transporter 8 mutations. 2589 25

Next-generation sequencing has enabled the screening for a causative mutation in X-linked intellectual disability (XLID). We identified KIAA2022 mutations in two unrelated male patients by targeted sequencing. We selected 13 Japanese male patients with severe intellectual disability (ID), including four sibling patients and nine sporadic patients. Two of thirteen had a KIAA2022 mutation. Patient 1 was a 3-year-old boy. He had severe ID with autistic behavior and hypotonia. Patient 2 was a 5-year-old boy. He also had severe ID with autistic behavior, hypotonia, central hypothyroidism, and steroid-dependent nephrotic syndrome. Both patients revealed consistent distinctive features, including upswept hair, narrow forehead, downslanting eyebrows, wide palpebral fissures, long nose, hypoplastic alae nasi, open mouth, and large ears. De novo KIAA2022 mutations (p.Q705X in Patient 1, p.R322X in Patient 2) were detected by targeted sequencing and confirmed by Sanger sequencing. KIAA2022 mutations and alterations have been reported in only four families with nonsyndromic ID and epilepsy. KIAA2022 is highly expressed in the fetal and adult brain and plays a crucial role in neuronal development. These additional patients support the evidence that KIAA2022 is a causative gene for XLID.
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PMID:Delineation of the KIAA2022 mutation phenotype: two patients with X-linked intellectual disability and distinctive features. 2590 Mar 96


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