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

We report two children with a common pattern of birth defects. Both have very sparse, curly hair, nystagmus and mental retardation. The first one has Noonan syndrome habitus associated with keratosis plantaris and nystagmus; the second one has a slightly Noonan-like face, macrocephaly, keratosis pilaris, and hypertrophic cardiomyopathy. They represent the extreme of a spectrum of congenital defects recently reported independently as CFC syndrome by Reynolds and as "Noonan-like short stature syndrome with sparse hair" by Baraitser and Patton. The clinical features are reviewed and the autonomy of the syndrome with regards to Noonan syndrome, is disputed, since every sign seems to occur independently in Noonan syndrome. The father of the second case probably has a minor syndrome expression, pointing to probable autosomal dominant inheritance.
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PMID:CFC syndrome: a syndrome distinct from Noonan syndrome. 326 6

A boy with characteristic facial features, pulmonary valvular stenosis, ectodermal abnormalities, growth failure, and mental retardation was admitted for intestinal occlusion at 20 months of age. Clinical findings were consistent with a diagnosis of cardio-facio-cutaneous syndrome (CFC-s), and a huge abdominal mass was evident on computed tomography scan. A biopsy was performed, and embryonal rhabdomyosarcoma was diagnosed. Molecular analysis was performed by reverse transcription (RT) polymerase chain reaction (PCR) on tumor RNA to seek the chimerical transcript of the most common soft tissue sarcoma translocations and analyze neurofibromatosis 1 (NF1) gene expression. Translocations involving 1;13, 2;13, and 11;22 were not found, and the specific transcripts of the NF1 gene were present. Chemotherapy was implemented, but the child died 7 months later of tumor progression. Few patients with CFC-s have been described, and their follow-up is not well known. The association of CFC-s with rhabdomyosarcoma has not been reported previously, but other neoplasms have been reported in patients with Noonan syndrome, a condition similar to CFC-s. More observations are needed, but this and other reports suggest there could be a higher risk of malignancy in patients with syndromes in the Noonan phenotype category.
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PMID:Rhabdomyosarcoma in a patient with cardio-facio-cutaneous syndrome. 1113 27

Noonan syndrome (NS) and related disorders are autosomal dominant disorders characterized by heart defects, facial dysmorphism, ectodermal abnormalities, and mental retardation. The dysregulation of the RAS/MAPK pathway appears to be a common molecular pathogenesis of these disorders: mutations in PTPN11, KRAS, and SOS1 have been identified in patients with NS, those in KRAS, BRAF, MAP2K1, and MAP2K2 in patients with CFC syndrome, and those in HRAS mutations in Costello syndrome patients. Recently, mutations in RAF1 have been also identified in patients with NS and two patients with LEOPARD (multiple lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) syndrome. In the current study, we identified eight RAF1 mutations in 18 of 119 patients with NS and related conditions without mutations in known genes. We summarized clinical manifestations in patients with RAF1 mutations as well as those in NS patients withPTPN11, SOS1, or KRAS mutations previously reported. Hypertrophic cardiomyopathy and short stature were found to be more frequently observed in patients with RAF1 mutations. Mutations in RAF1 were clustered in the conserved region 2 (CR2) domain, which carries an inhibitory phosphorylation site (serine at position 259; S259). Functional studies revealed that the RAF1 mutants located in the CR2 domain resulted in the decreased phosphorylation of S259, and that mutant RAF1 then dissociated from 14-3-3, leading to a partial ERK activation. Our results suggest that the dephosphorylation of S259 is the primary pathogenic mechanism in the activation of RAF1 mutants located in the CR2 domain as well as of downstream ERK.
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PMID:Molecular and clinical analysis of RAF1 in Noonan syndrome and related disorders: dephosphorylation of serine 259 as the essential mechanism for mutant activation. 2005 57