1/8. Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3.We previously discovered a novel missense mutation (Lys650Met) in the tyrosine kinase domain of the fibroblast growth factor receptor 3 (FGFR3) gene in four unrelated individuals with a condition we called "severe achondroplasia with developmental delay and acanthosis nigricans" (SADDAN) [Tavormina et al., 1999: Am. J. Hum. Genet. 64:722-731]. Here we present a more detailed clinical account of the SADDAN phenotype. The FGFR3 Lys650Met mutation results in severe disturbances in endochondral bone growth that approach and overlap those observed in thanatophoric dysplasia, type I. However, this mutation is most often compatible with survival into adulthood. Other unusual bone deformities, such as femoral bowing with reverse (i.e., posterior apex) tibial and fibular bowing and "ram's horn" bowing of the clavicle, are also seen in some patients. In addition to skeletal dysplasia, progressive acanthosis nigricans, and central nervous system structural anomalies, seizures and severe developmental delays are observed in surviving SADDAN patients. Despite its location within the same FGFR3 codon as the thanatophoric dysplasia type II mutation (Lys650Glu) and a similar effect on constitutive activation of the FGFR3 tyrosine kinase, the Lys650Met is not associated with cloverleaf skull or craniosynostosis.- - - - - - - - - - ranking = 1keywords = thanatophoric, thanatophoric dysplasia, dysplasia (Clic here for more details about this article) |
2/8. Clinical and biochemical findings of a patient with thanatophoric dysplasia type I: additional finding of dicarboxylic aciduria.OBJECTIVE: A long-surviving thanatophoric dysplasia type I patient to age of 6 years is presented. RESULTS AND CONCLUSIONS: Molecular studies revealed a heterozygous point mutation, S249C in the fibroblast growth factor receptor 3 gene. Most of the clinical course was similar to previous reports, including hearing loss and acanthosis nigricans. Abnormal urinary excretion of dicarboxylic acids and 3-hydroxydicarboxylic acids was observed. We hypothesize that this was a consequence of the FGFR3 mutation.- - - - - - - - - - ranking = 2.4998034463457keywords = thanatophoric, thanatophoric dysplasia, dysplasia (Clic here for more details about this article) |
3/8. ectodermal dysplasia with acanthosis nigricans (Lelis syndrome).A 31-year-old male patient with ectodermal dysplasia and acanthosis nigricans is described. Clinical findings included hypotrichosis, hypohidrosis, palmoplantar hyperkeratosis, nail dystrophy, early onset loss of permanent dentition, mental retardation, and acanthosis nigricans. The findings suggest the diagnosis of Lelis syndrome, as described on the basis of seven unrelated cases. A review concerning this condition is also presented.- - - - - - - - - - ranking = 7.8621461704386E-5keywords = dysplasia (Clic here for more details about this article) |
4/8. Somatic and germline mosaicism for a R248C missense mutation in FGFR3, resulting in a skeletal dysplasia distinct from thanatophoric dysplasia.In this communication, we report the identification of a mosaic R248C missense mutation in the IgII-III linker region of the gene encoding the fibroblast growth factor receptor-3 (FGFR3), in an individual who manifests a skeletal dysplasia and epidermal hyperplasia. By means of Denaturing High Performance Liquid chromatography (DHPLC), we determined that 25% of her lymphocytes are heterozygous for this particular missense mutation in FGFR3, and that 12.5% of her lymphocyte-derived genomic dna encodes a cysteine residue at this position. The proposita has disproportionate short stature, radial head dislocation, coxa vara, and bowing of some of the long bones, associated with an S-shaped deformity of the humerus, accompanied by widespread acanthosis nigricans in the integument. These features do not match any previously described skeletal dysplasia. Further, the proposita's only pregnancy ended in the delivery of a fetus manifesting a lethal short-limbed dwarfism with pulmonary hypoplasia, strongly suggestive of an undiagnosed thanatophoric dysplasia. These findings confirm the proposita to be a somatic and germline mosaic for this particular missense mutation in FGFR3. Thus far, all reported FGFR3 R248C mutations have resulted in thanatophoric dysplasia type I (TDI).- - - - - - - - - - ranking = 2.9998584813689keywords = thanatophoric, thanatophoric dysplasia, dysplasia (Clic here for more details about this article) |
5/8. ectodermal dysplasia with acanthosis nigricans (Lelis' syndrome).Autosomal recessive ectodermal dysplasia with acanthosis nigricans is termed Lelis' syndrome. It is a rare condition and one case is described with overall clinical, dermatological and dental findings.- - - - - - - - - - ranking = 7.8621461704386E-5keywords = dysplasia (Clic here for more details about this article) |
6/8. EC syndrome in a girl with paracentric inversion (7)(q22.1;q36.3).Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome associated with a paracentric inversion of chromosome 7 in a 2-year-old Japanese girl is reported. She had sparse and light-brown hair, bilateral cleft lip and palate, fused lower incisors, a pigmented skin lesion at the neck, accessory nipples, limited extension of elbow joints and bilateral ectrodactyly of hands and feet. Cytogenetic studies demonstrated a balanced inv(7)(q22.1;q36.3) in the patient and her father. The association of EEC syndrome and inv(7) in the patient suggested a putative locus of the EEC syndrome gene either at 7q22.1 or 7q36.3, although a coincidental occurrence of the two conditions is an alternative explanation. A comparison with reported karyotypes in patients with EEC or isolated ectrodactyly favoured 7q22.1 as the locus. A normal phenotype of the father in our family might reflect reduced penetrance of the EEC syndrome or, possibly, reduced expression of a maternally-derived allele of the EEC syndrome gene through a genomic imprinting mechanism.- - - - - - - - - - ranking = 1.5724292340877E-5keywords = dysplasia (Clic here for more details about this article) |
7/8. A severe case of Beare-Stevenson syndrome and associated congenital deformities.A severe case of congenital anomalies is described, with several characteristics of Beare-Stevenson syndrome, such as cutis gyrata, acanthosis nigricans, craniofacial anomalies, ear defects, enlarged umbilical stump and anogenital anomalies. He does not have craniosynostosis or clover leaf skull, which has also been described in this syndrome. This patient also shows hands and feet anomalies, absence of skin adnexa in several locations and dental anomalies, which could suggest an associated ectodermal dysplasia.- - - - - - - - - - ranking = 1.5724292340877E-5keywords = dysplasia (Clic here for more details about this article) |
8/8. Long-term survival in typical thanatophoric dysplasia type 1.thanatophoric dysplasia (TD), a severe skeletal dysplasia, is virtually always lethal neonatally, although a few previous reports have documented survival up to 4.75 years. We present a patient with survival beyond age 9 years and summarize his growth, development and medical history. The common Arg248Cys mutation in the extracellular region of fibroblast growth factor receptor 3 (FGFR3) was identified, eliminating the possibility that his long-term survival is attributable to an atypical mutation. This patient (and at least one other TD long-term survivor) have a rare skin disorder, acanthosis nigricans, which also occurs in Crouzon syndrome when caused by a FGFR3 mutation. Therefore, any molecular model of the origin of acanthosis nigricans secondary to FGFR3 mutations must account for the association of diverse mutations and these cutaneous effects.- - - - - - - - - - ranking = 1.9998742056613keywords = thanatophoric, thanatophoric dysplasia, dysplasia (Clic here for more details about this article) |