Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tuberous sclerosis is characterized by the potential for hamartomatous growth in multiple organs. Common manifestations are hypomelanotic spots, facial angiofibromas, subependymal hamartomas, cortical tubers, cardiac rhabdomyomas, retinal hamartomas, and so on. Seizures and mental retardation are frequent. It is an autosomal dominant disease but there is a high percentage of spontaneous mutations. Neonatal diagnosis is exceptional. We report a case of a female term newborn who presented partial motor seizures at the third day of life. Physical examination revealed only a disturbance of cardiac rhythm. Echocardiography showed ventricular intramural rhabdomyomas. Magnetic resonance imaging disclosed periventricular subependymal nodules and cortical tubers. A retinal hamartoma was found in the right eye. At the age of 1 month, hypomelanotic spots were evident on the back skin. The patient had infantile spasms, followed by poorly controlled partial complex seizures together with severe psychomotor retardation. Examination of both parents was normal. We discuss the uncommon diagnosis of tuberous sclerosis during the neonatal period, as well as the exceptional mode of presentation of our patient, with seizures in the early neonatal period, a phenomenon rarely reported in the literature.
 ...
PMID:[Partial seizures in a newborn with tuberous sclerosis]. 1100 83

Hypothalamic hamartomas are non neoplastic lesions that may cause precocious puberty with or without complex seizures, personality disorders and mental retardation. We report a 14 years old male that had a precocious puberty at the age of 11 and a prolonged episode of altered sensorium with automatism, that was diagnosed as a complex seizure. Physical examination showed a sexual development classified as Tanner stage III-IV, a height of 168 cm and a weight of 61 kg. Neurological examination was normal. A CAT scan showed a 13 x 13 x 9 mm mass in the suprasellar cistern, between the infundibulum and the brain stem, without exerting a mass effect over adjacent structures. It was diagnosed as an hypothalamic hamartoma.
 ...
PMID:[Hypothalamic hamartoma causing precocious puberty: A case report]. 1177 45

The objective of this study was to evaluate the clinical and endocrine profile of patients with precocious puberty followed up in a tertiary care hospital. Records of 140 patients (114 girls, 26 boys) with precocious puberty were reviewed. Clinical features including age of onset, stage of pubertal development, presenting symptoms, features suggestive of CNS involvement and family history were analyzed. Endocrine investigations included basal and GnRH-stimulated levels of LH and FSH as well as 17OHP, DHEA, hCG and thyroid profile. Abdominal and pelvic ultrasonography and CNS imaging were correlated with clinical features. Girls outnumbered boys in this series (4.4:1). Neurogenic central isosexual precocious puberty (CIPP) was more common in boys (10 out of 18, 55.6%) than girls (16 out of 77, 20.8%). The most common cause of neurogenic CIPP was hypothalamic hamartoma present in five girls and four boys. Other causes of neurogenic CIPP included neurotuberculosis, pituitary adenoma, hydrocephalus, post radiotherapy, CNS tumors and malformations. Peripheral precocious puberty (PPP) was secondary to adrenal causes in boys and ovarian cysts in girls. Benign variants of precocious puberty, such as premature thelarche and premature adrenarche, were present in 23 and six girls, respectively. Hypothyroidism was present in four girls and McCune-Albright syndrome in one girl. Girls with neurogenic CIPP had a lower age of onset as compared to idiopathic CIPP (3.6 +/- 2.7 years vs 5.4 +/- 2.5 years, p = 0.014). The lowest age of onset was seen in girls with hypothalamic hamartoma (1.6 +/- 0.9 years). Forty-seven girls with CIPP (seven neurogenic and 40 idiopathic) presented after the age of 6 years. Features of CNS involvement, in the form of seizures, mental retardation, raised intracranial tension or focal neurological deficits, were present in seven girls (43.8%) and four boys (40%), and gelastic seizures were present in three children. Girls with CIPP had greater bone age advancement (3.4 +/- 1.5 years) and negative height standard deviation for bone age (-2.7 +/- 1.5) than those with PPP (1.9 +/- 1.6 years and -1.3 +/- 1.3) and premature thelarche (0.4 +/- 0.4 years and -0.8 +/- 0.8). Patients with neurogenic CIPP had significantly higher levels of baseline and GnRH-stimulated levels of LH and FSH and LH:FSH ratio than those with idiopathic CIPP. Occurrence of neurogenic CIPP in seven girls with an age of onset after 6 years emphasizes the need for CNS imaging in these girls contrary to the current recommendations. The fact that 65.6% cases of idiopathic CIPP presented after the age of 6 years raises the possibility that these patients may be physiological variants of normal puberty. Pointers to neurogenic CIPP included early age of onset in girls, clinical features of CNS involvement, and elevated basal and stimulated LH levels and LH:FSH ratio.
 ...
PMID:Precocious puberty: clinical and endocrine profile and factors indicating neurogenic precocity in Indian children. 1238 16

Pallister-Hall syndrome (PHS, MIM #146510) is characterized by central and postaxial polydactyly, hypothalamic hamartoma (HH), bifid epiglottis, imperforate anus, renal abnormalities, and pulmonary segmentation anomalies. It is inherited in an autosomal dominant pattern. Here, we describe a family with two affected children manifesting severe PHS with mental retardation, behavioral problems, and intractable seizures. Both parents are healthy, with normal intelligence, and have no malformations on physical, laryngoscopic, and cranial MRI exam. The atypical presentation of these children and the absence of parental manifestations suggested an autosomal recessive mode of inheritance or gonadal mosaicism. Sequencing of GLI3 revealed a two nucleotide deletion in exon 15 (c.3385_3386delTT) predicting a frameshift and premature stop at codon 1129 (p.F1129X) in the children while both parents have wild type alleles. Genotyping with GLI3 intragenic markers revealed that both children inherited the abnormal allele from their mother thus supporting gonadal mosaicism as the underlying mechanism of inheritance (paternity was confirmed). This is the first reported case of gonadal mosaicism in PHS. The severe CNS manifestations of these children are reminiscent of children with non-syndromic HH who often have progressive mental retardation with behavioral problems and intractable seizures. We conclude that the phenotypic spectrum of PHS can include severe CNS manifestations and that recurrence risks for PHS should include a proviso for gonadal mosaicism, though the frequency cannot be calculated from a single case report. Published 2003 Wiley-Liss, Inc.
 ...
PMID:Gonadal mosaicism in severe Pallister-Hall syndrome. 1470 4

Tuberous sclerosis - also called tuberous sclerosis complex (TSC) - is a rare, multi-system genetic disorder affecting cellular differentiation & proliferation, which results in hamartoma formation in many organs. The classic triad of clinical features comprises mental retardation, epilepsy & skin lesion, but these three features are not always present. Mrs. Jahanara Khatun, a 30 years old lady presented with maculo-papular skin lesions over the face, neck, shoulder since her six years of age, a lump in the right lumber region for four years, pain in the right lumber region associated with passage of blood clot in urine for 15 days. Her family history was very characteristic. One of her elder brother had developed same type of skin lesions. Again her 13 years old daughter had developed same type of skin lesions since seven years of age & she was mentally retarded. Clinical examination revealed normal mentation, pin head sized yellowish red translucent discrete waxy papules situated in the face, neck, shoulder. A large tender firm irregular mass in the right lumber region, which was ballotable & moved with respiration. USG revealed bilateral retroperitoneal masses with the involvement of right kidney & formation of renal artery aneurysm. The patient undergone right sided nephrectomy & histopathology of the specimen showed features suggestive of renal angiomyolipoma. The patient was diagnosed as a case of definite tuberous sclerosis complex as she had two major feature of revised diagnostic criteria - facial angiofibromas & renal angiomyolipoma.
 ...
PMID:Tuberous sclerosis. 1474 93

Uncontrolled rage, while long associated with hypothalamic hamartoma, has not been as extensively studied as the epilepsy. Rage can be more detrimental to quality of life than seizures. It is now realized that behavior and aggression improve after a complete resection of the hypothalamic hamartoma correlating with a good seizure control post-surgically. We report on the longitudinal psychiatric history of a patient with hypothalamic hamartoma and rage whose severe and refractory epilepsy was ultimately treated by thalamic and intrahamartoma chronic stimulation. Our patient did not exhibit sham rage typical of hypothalamic lesions, but rather multifactorial aggressive bouts typical of challenging behaviors seen with mental retardation. The anxious and social features of the aggression suggest that psychiatric interventions, which have been neglected as the emphasis has been on seizure control, are worthwhile in the overall management of this difficult case.
 ...
PMID:Psychiatric aspects of patients with hypothalamic hamartoma and epilepsy. 1497 91

We report the case of a woman presenting with unusual, symptomatic epilepsy related to a hypothalamic hamartoma, in the absence of mental retardation or precocious puberty. The seizures manifested themselves clinically as characteristic, paroxysmal movement disorders, such as choreic/ballistic movement. This type of phenomenon is rarely of epileptic origin: we thus suggest that the movement disorder observed here could be due to functional disorganization of the basal ganglia network by the epileptic discharge, causing loss of the inhibition of thalamic activity and thus allowing the occurrence of abnormal movements.
 ...
PMID:Ictal movement disorders and hypothalamic hamartoma. 1574 Nov 40

The authors report the case of a 12-year-old girl with Pallister-Hall syndrome, long-standing refractory, symptomatic epilepsy, mental retardation, and panhypopituitarism in whom two rare, deep midline lesions were detected. She underwent successful transsphenoidal resection of the Rathke cleft cyst and transcallosal resection of the hypothalamic hamartoma within a 4-day period without complications. Neuropathological studies confirmed the neuroimaging diagnoses for the two lesions. The patient has been seizure free for 6 months postoperatively.
 ...
PMID:Successful resection of a hypothalamic hamartoma and a Rathke cleft cyst. Case report. 1620 38

Tuberous sclerosis (TSC) is a hamartoma syndrome attributable to mutations in either TSC1 or TSC2 in which brain involvement causes epilepsy, mental retardation, and autism. We have reported recently (Meikle et al., 2007) a mouse neuronal model of TSC in which Tsc1 is ablated in most neurons during cortical development. We have tested rapamycin and RAD001 [40-O-(2-hydroxyethyl)-rapamycin], both mammalian target of rapamycin mTORC1 inhibitors, as potential therapeutic agents in this model. Median survival is improved from 33 d to more than 100 d; behavior, phenotype, and weight gain are all also markedly improved. There is brain penetration of both drugs, with accumulation over time with repetitive treatment, and effective reduction of levels of phospho-S6, a downstream target of mTORC1. In addition, there is restoration of phospho-Akt and phospho-glycogen synthase kinase 3 levels in the treated mice, consistent with restoration of Akt function. Neurofilament abnormalities, myelination, and cell enlargement are all improved by the treatment. However, dysplastic neuronal features persist, and there are only modest changes in dendritic spine density and length. Strikingly, mice treated with rapamycin or RAD001 for 23 d only (postnatal days 7-30) displayed a persistent improvement in phenotype, with median survival of 78 d. In summary, rapamycin/RAD001 are highly effective therapies for this neuronal model of TSC, with benefit apparently attributable to effects on mTORC1 and Akt signaling and, consequently, cell size and myelination. Although caution is appropriate, the results suggest the possibility that rapamycin/RAD001 may have benefit in the treatment of TSC brain disease, including infantile spasms.
 ...
PMID:Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. 1912 12

Tuberous sclerosis (TS) is a multisystem disorder characterized by hamartomas in various organs. It usually manifests itself during infancy or childhood with neurological features, including mental retardation and seizures. We present the case of a military pilot who was diagnosed with TS at 22 yr. of age after he had completed flight training. Suspicion of TS arose from evaluation of a chronic rash around the pilot's nose, and diagnosis was confirmed based on the presence of multiple calcified nodules on CT imaging of the brain. No neurological abnormalities were found. The primary aeromedical concerns were the risk of seizures or development of tumors at sites that might lead to sudden incapacitation. Hamartomas can be reliably detected at an early stage by means of annual history, physical examination, and imaging of tumor-prone organs. After review of the literature and consultation with medical specialists, we assessed the risk of adult-onset seizures in a TS patient without preexisting neurological findings as scarce. The pilot was therefore granted a waiver limited to flying a two-pilot helicopter with a program of tight medical follow-up.
 ...
PMID:Tuberous sclerosis in a military pilot. 1960 10


<< Previous 1 2 3 Next >>