1/21. Hutchinson-Gilford progeria syndrome.Hutchinson-Gilford progeria syndrome is an extremely rare condition of premature aging. It is characterized by growth retardation and accelerated degenerative changes of cutaneous, musculoskeletal and cardiovascular systems. The pathogenesis of the disease is unknown. The patients usually appear normal at birth. Typical manifestations develop gradually and are evident by the first or second year of life. They have a remarkably similar physical appearance consisting of short stature, alopecia, craniofacial disproportion, micrognathia, hypoplastic mandible, beak-like nose, decreased subcutaneous fat, atrophic skin, sclerodermoid lesion, mottling hyperpigmentation, prominent scalp veins, prominent eyes, protruding ears with absence of earlobes, faint midfacial cyanosis, delayed closure of fontanelles and sutures, delayed dentition, horse-riding stance, thin limbs with prominent stiff joints, coxa valga, skeletal hypoplasia and dysplasia, dystrophic nails and high-pitched voice. Laboratory investigations are unremarkable. Metabolic, endocrine, serum lipid and immunologic studies show no uniform abnormalities. Typical radiographs demonstrate evidence of resorption of the distal ends of clavicles, attenuation of the terminal phalanges, diffuse osteopenia, and fishmouth vertebral bodies. In this report, a 3-year-old Thai girl with typical characteristics of Hutchinson-Gilford progeria syndrome is described.- - - - - - - - - - ranking = 1keywords = subcutaneous fat, fat (Clic here for more details about this article) |
2/21. Lethal neonatal Hutchinson-Gilford progeria syndrome.We report on a 35-week gestation female fetus with Hutchinson-Gilford progeria (HGP). This patient, who is the first reported with neonatal HGP in the English literature but is the fourth, counting three previous French cases, supports the existence of a more severe prenatal form of progeria. She died 7 hours after birth and presented with intrauterine growth retardation, premature aging, absence of subcutaneous fat, brachydactyly, absent nipples, hypoplastic external genitalia, and abnormal ear lobes. The child's combination of clinical and skeletal manifestations differentiates this form of HGP from other progeroid syndromes with neonatal presentation. We also report previously undescribed autopsy findings including premature loss of hair follicles, premature regression of the renal nephrogenic layer, and premature closure of the growth plates in the distal phalanges that may be related to the aging processes in this condition. We could not find any histological data to support acro-osteolysis, which is the radiographic sign of brachydactyly. The terminal phalanges in HGP seem to be underdeveloped rather than osteolytic.- - - - - - - - - - ranking = 1keywords = subcutaneous fat, fat (Clic here for more details about this article) |
3/21. Neonatal progeroid (Wiedemann-Rautenstrauch) syndrome: report of five new cases and review.The neonatal progeroid syndrome (NPS), or Wiedemann-Rautenstrauch, is a rare autosomal recessive disorder comprised of generalized lipoatrophy except for fat pads in the suprabuttock areas, hypotrichosis of the scalp hair, eyebrows, and eyelashes, relative macrocephaly, triangular face, natal teeth, and micrognathia. We report on 5 new patients who demonstrate phenotypic variability and who represent the single largest series of NPS reported to date. Two of the patients are from an African-American kindred, an ethnic occurrence not reported previously. The fact that there are 2 pairs of sibs among the 5 patients further supports that NPS is an autosomal recessive condition. This report also includes a review of the previously reported 16 patients and compares them with the 5 new patients. Abnormalities in endocrine and lipid metabolism were found in 3 of 5 patients. Skeletal findings in 2 of our patients demonstrated some new findings as well as the typical radiological abnormalities previously noted in NPS. It is apparent, based on the 21 cases, that mild to moderate mental retardation is common in NPS. Long term follow-up of patients with NPS should provide more information relative to their ultimate psychomotor development. NPS is usually lethal by 7 months; however, on rare occasions, patients have survived into the teens. Our 3 surviving patients range in age from 16-23 months. Variability in the phenotype of NPS is clear; however, the phenotype remains distinct enough to allow a secure diagnosis.- - - - - - - - - - ranking = 0.00114295160593keywords = fat (Clic here for more details about this article) |
4/21. Wiedemann-Rautenstrauch (neonatal progeroid) syndrome: new case with normal telomere length in skin fibroblasts.Wiedemann-Rautenstrauch (neonatal progeroid) syndrome is an autosomal recessive condition with characteristic appearance of premature aging present at birth (aged face, natal teeth, and wrinkled skin). Other features of the syndrome are generalized lipoatrophy with specific fat accumulation in the lateral suprabuttock region, hypotrichosis, macrocephaly (pseudohydrocephalus), and mental retardation. We report on a new case that demonstrates all typical features of the syndrome. The girl is now 16 years and 10 months old and has had follow-up from birth. We measured terminal restriction fragment (TRF) length to evaluate whether the patient's premature aging process is accompanied by shortening of telomere length in her cultured fibroblasts. Mean TRF of 13.5 kb found in our patient's fibroblasts is not shortened as compared to that of normal fibroblasts. Our results differ from those observed in Hutchinson-Gilford progeria.- - - - - - - - - - ranking = 0.00114295160593keywords = fat (Clic here for more details about this article) |
5/21. Hutchinson-Gilford progeria syndrome: a pathologic study.Hutchinson-Gilford progeria syndrome is an extremely rare condition with features of premature and accelerated aging. The pattern of inheritance if unclear, although both autosomal recessive and autosomal dominant modes have been proposed. The children usually present in late infancy and early childhood with a characteristic phenotype of alopecia; short stature; abnormal skin, teeth, and nails; beaked nose; loss of subcutaneous fat; and failure to thrive. This condition has been reported on all inhabited continents and has been described in all major races. Laboratory findings note an increased urinary excretion of hyaluronic acid. death results from cardiovascular abnormalities in the majority of cases and usually occurs in the second decade of life. There is no effective treatment. We report the pathologic changes noted at autopsy on a 20-year-old woman with classic features of Hutchinson-Gilford progeria syndrome.- - - - - - - - - - ranking = 1keywords = subcutaneous fat, fat (Clic here for more details about this article) |
6/21. Fatal pulmonary hypertension associated with an atypical case of Hunchinson-Gilford progeria.We report the first autopsied case of an incomplete type of Hunchinson-Gilford progeria associated with fatal pulmonary hypertension. Histopathologic findings revealed abnormal deposition of collagen and elastic fibers, as well as cellular proliferation, at intima of the coronary arteries, pulmonary small arteries, and arterioles. These changes could be underlying conditions of the association of the two diseases.- - - - - - - - - - ranking = 0.00114295160593keywords = fat (Clic here for more details about this article) |
7/21. Severe bone changes in a case of Hutchinson-Gilford syndrome.The Hutchinson-Gilford progeria syndrome (HGPS) is a very rare, but well known inherited condition of uncertain etiology in which features of premature and accelerated aging are mixed with those of delayed maturity and immaturity. Appearance at birth and birth weight are usually normal but growth typically slows after 1 year. All organ systems undergo degeneration to such an extent that the patient resembles an old man or woman. Short stature, micrognatia, alopecia, sculptured nose, prominent scalp veins, loss of subcutaneous fat, prominent joints, hyperlipidemia and early arteriosclerosis characterize the syndrome. Skeletal compromise includes hypoplasia and dysplasia, persistent open fontanelles, severe osteolysis and pathological fractures. There are no intellectual deficits in patients with this syndrome, and intelligence is unaffected. The life span in progeria is shortened by early arteriosclerosis. In this case, we review the characteristics of the severe osteolytic compromise in distal arms and limbs and bone deformities in a case of an 8-year-old girl, who was admitted to our hospital with short stature and loss of hair. On examination, the child had the major clinical criteria for HGPS as well as severe alterations in osteogenesis, including craniofacial disproportion, short and sculptured nose, delayed dentition, severe scoliosis, clavicular deformity and asymmetrical and hypoplastic arms and legs. Generalized osteopenia and severe osteolytic compromise in distal extremities were found by X-ray examination. In summary, we report the case of an 8-year-old girl who meets the diagnostic criteria for HGPS with severe involvement of her bones and joints with a review of the current literature and a possible therapeutic approach.- - - - - - - - - - ranking = 1keywords = subcutaneous fat, fat (Clic here for more details about this article) |
8/21. Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress.BACKGROUND: Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare sporadic disorder with an incidence of approximately 1 per 8 million live births. The phenotypic appearance consists of short stature, sculptured nose, alopecia, prominent scalp veins, small face, loss of subcutaneous fat, faint mid-facial cyanosis, and dystrophic nails. HGPS is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. The most common mutation in subjects with HGPS is a de novo single-base pair substitution, G608G (GGC>GGT), within exon 11 of LMNA. This creates an abnormal splice donor site, leading to expression of a truncated protein. RESULTS: We studied a new case of a 5 year-old girl with HGPS and found a heterozygous point mutation, G608G, in LMNA. Complementary dna sequencing of rna showed that this mutation resulted in the deletion of 50 amino acids in the carboxyl-terminal tail domain of prelamin A. We characterized a primary dermal fibroblast cell line derived from the subject's skin. These cells expressed the mutant protein and exhibited a normal growth rate at early passage in primary culture but showed alterations in nuclear morphology. Expression levels and overall distributions of nuclear lamins and emerin, an integral protein of the inner nuclear membrane, were not dramatically altered. Ultrastructural analysis of the nuclear envelope using electron microscopy showed that chromatin is in close association to the nuclear lamina, even in areas with abnormal nuclear envelope morphology. The fibroblasts were hypersensitive to heat shock, and demonstrated a delayed response to heat stress. CONCLUSION: Dermal fibroblasts from a subject with HGPS expressing a mutant truncated lamin A have dysmorphic nuclei, hypersensitivity to heat shock, and delayed response to heat stress. This suggests that the mutant protein, even when expressed at low levels, causes defective cell stability, which may be responsible for phenotypic abnormalities in the disease.- - - - - - - - - - ranking = 1keywords = subcutaneous fat, fat (Clic here for more details about this article) |
9/21. Agrypnia excitata in a patient with progeroid short stature and pigmented Nevi (Mulvihill-Smith syndrome).We report the video-polysomnographic sleep characteristics of a 25-year-old woman with the Mulvihill-Smith syndrome, a rare clinical condition characterized by progeria-like aspect, peculiar multiple pigmented nevi, low stature, and cognitive impairment. Among the various exams, two overnight video-polysomnographic recordings were carried out; moreover, cerebral MRI and molecular analysis of the prion protein gene (PRNP) were also performed. The video-polysomnographic recordings showed the absence of clear sleep episodes but the presence of periods during which the patient had poor contact with the environment, stereotyped afinalistic movements of the upper limbs and hands, irregular or periodic breathing (with central apnea episodes), heart rate arrhythmia, and rapid eye movements. Cerebral MRI showed only diffuse mild enlargement of the cortical sulci and the molecular genetics analysis of the PRNP was normal. Our clinical and neurophysiological study seems to indicate that a particular condition of severe sleep disruption, similar to some extent to that reported in the fatal familial insomnia and in the Morvan fibrillary chorea, which has been indicated as Agrypnia Excitata in recent literature, might be associated with the Mulvihill-Smith syndrome. The inclusion of a detailed study on the sleep characteristics of eventual additional patients will certainly help our understanding of this rare condition.- - - - - - - - - - ranking = 0.00114295160593keywords = fat (Clic here for more details about this article) |
10/21. Abnormal gene expression in skin fibroblasts from a Hutchinson-Gilford patient.We had the opportunity to investigate a new case of Hutchinson-Gilford progeria, a rare disease commonly regarded as a model in the study of aging. Two strains of fibroblasts (strains 1 and 2) were derived from two pieces of a skin biopsy. These two populations multiplied as normal cells at low population doubling level but senesced rapidly and stopped proliferating after 14 or 15 population doubling levels. Interestingly, an unusual pattern of growth in clusters was observed for strain 1. The level of collagen and noncollagen protein synthesis of both strains of affected fibroblasts was similar to that of normal fibroblasts as determined by [3H]proline incorporation measurement and was similarly affected by varying serum concentrations. The pattern of the main types of newly synthesized collagen polypeptides analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was similar in normal and progeria cells. The steady-state level of mRNAs coding for macromolecules of the extracellular matrix did not provide any differences between affected and control fibroblasts except for a strong increase of elastin and of alpha 1 and alpha 2 type IV procollagen mRNA mainly in strain 1 and less marked in strain 2. Interestingly, senescent progeria fibroblasts exhibited a reduced level of all the tested mRNAs, whereas collagen type iv and elastin mRNAs remained elevated. As suggested by immunofluorescence and immunoblotting studies, the increased amount of type IV mRNAs was paralleled by an enhanced production of type IV collagen by fibroblasts in vitro. Histologic examination of the skin revealed a superabundant network of abnormal elastic fibers in the reticular dermis and a thickening of basement membranes. The relationship between these alterations and aging in progeria is discussed.- - - - - - - - - - ranking = 0.00114295160593keywords = fat (Clic here for more details about this article) |
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