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)

The police brought a 65-year-old female patient to the EADU after being found 'roaming the streets' in an apparent state of confusion. This was her third admission under the same circumstances during the last 3 years. Neurological examination revealed (1) cognitive impairment, (2) oculomotor apraxia, (3) abnormal cancellation of vestibular ocular reflex, (4) mild ataxia and (5) mild hypotonia. Renal function was abnormal and liver function was normal. No retinal disturbance was found. The head CT on admission was normal for stroke and the lumbar puncture was negative for encephalitis. Her brain MRI showed 'molar tooth sign', suggestive of Joubert syndrome, which was confirmed by genetic testing showing anomalous NPHP1 gene.
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PMID:An elusive ciliopathy: Joubert syndrome. 2866 57

The Dravet Syndrome Foundation (DSF) conducted the largest in-depth survey of parents and caregivers of patients with Dravet syndrome (DS) to date, in order to (1) identify top concerns among caregivers, (2) establish an approximate frequency of characteristics and comorbidities of DS beyond seizures, and (3) provide direction for clinicians and researchers looking to study the effects of DS on the patient and family unit. Two hundred fifty-six responses were received representing a patient age range of 9months to 32years with a median age group of 7-10years (IQR=8). In an open response, caregivers ranked speech/communication, impacts on siblings, and cognitive impairment as their top concerns after seizure control, and nearly two-thirds of caregivers reported having suffered from depression. Some characteristics of DS such as gait issues increased with patient age, while others, including photosensitivity, hypotonia, and ataxia, were present from a young age. Comorbidities such as sleep disturbances and cardiac abnormalities were more frequently reported than in previous studies and some (including bradycardia) were correlated with SCN1A mutation status. This survey supports the concept of Dravet syndrome as a disease of the central nervous system with far-reaching effects and highlights the importance of the patient voice in determining appropriate research objectives. While seizure frequency is a relatively well-understood objective, seizures represent only a portion of parent and caregiver concerns. Studying the characteristics of DS described herein may identify additional outcomes significant for research.
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PMID:Dravet syndrome: Characteristics, comorbidities, and caregiver concerns. 2873 59

Smith-Magenis syndrome (SMS; OMIM #182290) is a complex genetic disorder characterized by distinctive physical features, developmental delay, cognitive impairment, and a typical behavioral phenotype. SMS is caused by interstitial 17p11.2 deletions, encompassing multiple genes and including the retinoic acid-induced 1 gene (RAI1), or by mutations in RAI1 itself. About 10% of all the SMS patients, in fact, carry an RAI1 mutation responsible for the phenotype. RAI1 (OMIM *607642) is a dosage-sensitive gene expressed in many tissues and highly conserved among species. Over the years, several studies have demonstrated that RAI1 (or its homologs in animal models) acts as a transcriptional factor implicated in embryonic neurodevelopment, neuronal differentiation, cell growth and cell cycle regulation, bone and skeletal development, lipid and glucose metabolisms, behavioral functions, and circadian activity. Patients with RAI1 pathogenic variants show some phenotypic differences when compared to those carrying the typical deletion. They usually have lower incidence of hypotonia and less cognitive impairment than those with 17p11.2 deletions but more frequently show the behavioral characteristics of the syndrome and overeating issues. These differences reflect the primary pathogenetic role of RAI1 without the pathogenetic contribution of the other genes included in the typical 17p11.2 deletion. The better comprehension of physiological roles of RAI1, its molecular co-workers and interactors, and its contribution in determining the typical SMS phenotype will certainly open a new path for therapeutic interventions.
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PMID:RAI1 gene mutations: mechanisms of Smith-Magenis syndrome. 2913 88

Prader-Willi syndrome (PWS) is a complex genetic imprinting disorder characterized by childhood obesity, short stature, hypogonadism/hypogenitalism, hypotonia, cognitive impairment, and behavioral problems. Usually PWS occurs sporadically due to the loss of paternally expressed genes on chromosome 15 with the majority of individuals having the 15q11-q13 region deleted. Examples of familial PWS have been reported but rarely. To date 13 families have been reported with more than one child with PWS and without a 15q11-q13 deletion secondary to a chromosome 15 translocation, inversion, or uniparental maternal disomy 15. Ten of those 13 families were shown to carry microdeletions in the PWS imprinting center. The microdeletions were found to be of paternal origin in nine of the ten cases in which family studies were carried out. Using a variety of techniques, the microdeletions were identified in regions within the complex SNRPN gene locus encompassing the PWS imprinting center. Here, we report the clinical and genetic findings in three adult siblings with PWS caused by a microdeletion in the chromosome 15 imprinting center inherited from an unaffected father that controls the activity of genes in the 15q11-q13 region and summarize the 13 reported cases in the literature.
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PMID:Three siblings with Prader-Willi syndrome caused by imprinting center microdeletions and review. 2943 85

Zic family proteins have been investigated in various biomedical studies. Here we summarize the contact points between Zic proteins and recent medical research. The topics cover a wide range, reflecting the pleiotropic roles of these proteins in early embryogenesis and organogenesis. Zic1, Zic2, and Zic3 proteins play important roles in the development of axial and limb bones, and of muscles, among the derivatives of the notochord and somites. Zic1 is involved in bone's response to mechanical stress, and it also serves as a marker specific for brown adipocytes. Zic1, Zic2, Zic3, and Zic5 proteins are required for the development of neural crest derivatives, including the meningeal membrane and facial bones, and deficiency of these proteins causes cortical lamination defects resembling those in type II lissencephaly. In vascular systems, Zic3 is associated not only with normal cardiovascular development, failure of which causes congenital heart anomalies, but also controls maturation of the blood-brain barrier. Zic1 is also expressed in the brain pericytes possessing stem cell properties that control the blood-brain barrier activity and capillary hemodynamic responses. The possible involvement of Zic proteins in neuropsychiatric disorders has been indicated by the analyses of mutant mice behaviors. Zic1 and Zic3 mutant mice show hypotonia and decreased locomotor activities. Zic2 hypomorphic mutant mice exhibit schizophrenia-related behavioral abnormalities such as cognitive dysfunction and impaired sensorimotor gating and social behaviors, and ZIC2 mutations found in schizophrenia patients included a severely functionally defective one. Based on these facts, the application of Zic protein activities in translational medicine might be considered.
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PMID:Zic Family Proteins in Emerging Biomedical Studies. 2944 25

Tetrasomy 18p syndrome (Online Mendelian Inheritance in Man 614290) is a very rare chromosomal disorder that is caused by the presence of isochromosome 18p, which is a supernumerary marker composed of two copies of the p arm of chromosome 18. Most tetrasomy 18p cases are de novo cases; however, familial cases have also been reported. It is characterized mainly by developmental delays, cognitive impairment, hypotonia, typical dysmorphic features, and other anomalies. Herein, we report de novo tetrasomy 18p in a 9-month-old boy with dysmorphic features, microcephaly, growth delay, hypotonia, and cerebellar and renal malformations. We compared our case with previously reported ones in the literature. Clinicians should consider tetrasomy 18p in any individual with dysmorphic features and cardiac, skeletal, and renal abnormalities. To the best of our knowledge, we report for the first time an association of this syndrome with partial agenesis of cerebellar vermis.
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PMID:Tetrasomy 18p: case report and review of literature. 2946 81

Allan-Herndon-Dudley syndrome is a rare X-linked neurologic condition caused by mutations in monocarboxylate transporter 8 ( MCT8), which leads to deficient thyroid hormone transport. Typical features include severe cognitive impairment, truncal hypotonia, spastic paraplegia, weakness, and speech difficulties. Minimal literature exists describing the ocular findings in patients with Allan-Herndon-Dudley syndrome. We describe 4 male siblings affected with Allan-Herndon-Dudley syndrome with a novel nonsense mutation (Q90X) in the MCT8 protein. All affected siblings presented with classic findings of Allan-Herndon-Dudley syndrome, and each of the siblings also developed intermittent esotropia. This group of affected siblings represents the first consistent documentation of strabismus in Allan-Herndon-Dudley syndrome, suggesting a possible association between this clinical finding and the neurologic syndrome.
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PMID:Intermittent Esotropia in 4 Patients With Allan-Herndon-Dudley Syndrome. 2971 7

49,XXXXY syndrome is a rare sex chromosome aneuploidy syndrome. Cognitive impairment with expressive language deficits in combination with developmental and speech dyspraxia are cardinal symptoms. Testicular insufficiency becomes apparent during adolescence. Neurological, musculoskeletal, genital, orthodontic and immunological anomalies are common and a higher incidence of congenital malformations has been described. Here we show the evolving clinical and facial phenotype of eight boys and men with 49,XXXXY, demonstrating an increasingly perceptible distinct facial gestalt over time. In addition, almost all patients had muscular hypotonia, radioulnar synostosis, white matter anomalies, fifth-finger clinodactyly, recurrent respiratory infections in early childhood and teeth anomalies. IQ scores ranged between 40 and 70. Though many boys showed short stature at some point in early childhood, most outgrew it. As more long term data of boys and men with 49,XXXXY become available, parents of affected boys can be counseled more specifically as to the expected course and spectrum of this rare chromosomal disorder. Moreover, the multidisciplinary support can be optimized und unnecessary diagnostics avoided.
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PMID:Clinical report of 8 patients with 49,XXXXY syndrome: Delineation of the facial gestalt and depiction of the clinical spectrum. 3003 Nov 53

The Joubert syndrome is characterized by hypotonia, ataxia, facial dysmorphism, abnormal eye movement, irregular breathing pattern and cognitive impairment. The molar tooth sign is the pathognomonic midbrain-hindbrain malformation for Joubert syndrome. Joubert syndrome and related disorders (JSRD), are the clinically and genetically heterogen disorders in which the obligatory hallmark is the molar tooth sign (MTS). In this report, it was described the association of the molar tooth sign, absence of pituitary gland and corpus callosum agenesis on an infant with JSRD. To the best of our knowledge, this is the first case diagnosed as JSRD and panhypopituitarism without features of OFD VI.
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PMID:AN UNUSUAL PRESENTATION OF JOUBERT SYNDROME AND RELATED DISORDERS IN A NEWBORN: PANHYPOPITUITARISM. 3020 65

Prader-Willi syndrome is a neurogenetic disorder characterized by a number of signs and symptoms, including muscular hypotonia in infancy, hypogonadism, obesity and short stature. Neurobehavioral abnormalities and cognitive impairment are common. In addition, breathing abnormalities have been described, including sleep-related breathing disorders, abnormal chemoreceptor sensitivity and pulmonary function abnormalities. Growth hormone treatment is now widely used in children with Prader-Willi syndrome to improve growth and body composition. Over the last 4 years, case reports have been published concerning unexpected death, many of which were related to respiratory abnormalities. This review focuses on breathing abnormalities in Prader-Willi syndrome individuals and the influence of obesity, growth hormone treatment and upper respiratory tract infections.
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PMID:Breathing disorders in Prader-Willi syndrome: the role of obesity, growth hormone treatment and upper respiratory tract infections. 3029 Apr 25


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