Senile Appearance Research Articles

Neonatal Marfan syndrome: a case report of a novel fibrillin 1 mutation, with genotype-phenotype correlation and brief review of the literature

BackgroundNeonatal Marfan syndrome (nMFS) is a rare condition characterized by severe phenotype and poor prognosis. nMFS is caused by mutations in a specific region of the fibrillin 1 gene (FBN1). Prompt recognition of typical signs of neonatal presentation, such as characteristic facial anomalies with senile appearance, arthrogryposis, and campto-arachnodactyly, is fundamental for performing an early cardiological examination. This usually reveals rapidly progressive cardiovascular disease due to severe atrioventricular valve dysfunction.Case presentationHerein, we report the case of an early-onset cardiac failure in a neonate with Marfan syndrome, with a brief review of the literature of cases with cardiac involvement in neonatal age. Clinical exome sequencing identified the novel heterozygous de novo missense variant c.3152T > G in FBN1 gene (NM_000138.4), causing the aminoacidic change p.Phe1051Cys. Phenotype-genotype correlation led to a multidisciplinary diagnostic and management workflow.ConclusionThe prompt recognition of a typical phenotype such as that of Marfan syndrome should lead to a detailed evaluation and close follow-up of cardiac morphology and function. Indeed, multi-disciplinary evaluation based on genotype-phenotype correlations of nMFS cases is essential to finding out the best medical and surgical approach, predicting the relevant impact on patient prognosis, and adequately counseling their families.

Neonatal presentation of Loeys-Dietz syndrome: two case reports and review of the literature

BackgroundLoeys-Dietz syndrome (LDS) is a rare connective tissue disorder characterized by cardiovascular manifestations, especially aortic dilatations and arterial tortuosity, craniofacial and skeletal features, joint laxity or contractures, skin abnormalities, hypotonia and motor delay. Its diagnosis is established by the identification of a pathogenic variant in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2 or TGFB3 genes. In newborns and toddlers, vascular complications such as aneurism rupture, aortic dissection, and intracerebral incidents, can occur already in the weeks of life. To avoid these events, it is crucial to precociously identify this condition and to start an apunderwent a surgical procedurepropriate treatment which, depending on the severity of the vascular involvement, might be medical or surgical.Case presentationWe report two cases of Loeys-Dietz syndrome precociously diagnosed. The first describes a male, born at 38 + 1 weeks of gestation, with hypotonia, joint hypermobility, arachnodactyly, and fingers joint contractures, as well as senile appearance and facial dysmorphisms. In the suspect of a connective tissue disorder, an echocardiography was performed and revealed an aortic root dilatation of 13 mm (Z score + 3). A trio based Whole Exome Sequencing found a novel de novo variant in the TGFBR2 gene. Despite the onset of a low-dose angiotensin receptor blocker therapy, the aneurysm progressed. The second case describes a female, born at 41 + 3 weeks of gestation. During the neonatal examination a cleft palate was noticed, as well as minor dysmorphisms. Since the family history was suspicious for connective tissue disorders, a genetic panel was performed and identified a pathogenetic variant in TGFB3 gene. In this case, the echocardiography revealed no abnormalities.ConclusionsIn addition to our cases, we identified 14 subjects with neonatal LDS in the medical literature. All of them had aortic involvement. Skeletal and face abnormalities, including eyes and palate malformations, were also highly frequent. Overall, 10 subjects required medical therapy to avoid aneurysm progression, and 8 patients underwent surgical procedures.Benefits of an early diagnosis of LDS are various and imply a potential modification of the natural history of the disease with early interventions on its complications.

Clinical cases of child progeria

Child progeria is an extremely rare disease. Not every dermatologist is lucky enough to work with such a diagnosis during medical practice.The first case of child progeria was described in 1886 by the English doctor J. Hutchinson at a 6 years old child. 11 years later, H. Gilford entered the term «progeria» in medical terminology as a syndrome of premature aging of the human body. The etiology of this illness is not clear. The hereditary nature of the disease has not been traced, but there is an opinion about the autosomal-recessive type of inheritance. The average life expectancy of the patients with progeria is 15—16 years.Progeria is characterized by growth retardation, signs of rapid aging. At birth or in the first years of life, geroderma develops, that is, drawn, wrinkled, dry, parchment­like skin, yellow with a brown color tinge, through which the superficial venous net is often visible. The child looks like a deep elder — a small face, a beak­shaped nose. The skin hangs, the muscles are atrophied, the hair is fine, greasy, falls out. For a long time milk teeth are stored, nail plates are thin, atrophic. The genital organs are underdeveloped. On a roentgenogram of tubular bones there is osteoporosis. The intellect is developed according to the age.For more than half a century of the pediatric practice we diagnosed only three cases of child progeria. The first case was described in 1991. The reports about two more patients aged 7 and 15 with child progeria were published.Many authors attempted to classify progeria, tried to differentiate forms of this disease. In our opinion, this is inappropriate due to the large number of clinical signs and inconsistency of them. We believe that the basic diagnostic criteria for child progeria should be highlighted, namely: sclerotic changes in the heart and blood vessels, senile appearance, wrinkled atrophic skin, loss of the hair and teeth, muscle atrophy, and others. Taking into account that the symptoms of aging at progeria appear at different ages, we consider it expedient to single out two forms of progeria — early and late. In case of early form the child is born with aging symptoms, which is obviously associated with genetic factors, fetal malformations, and mother’s illnesses during pregnancy. In the late version, rapid aging begins later, at the age of 2 or 3 years, and is associated with a violation of endocrine regulation.

Acquired partial lipodystrophy: An atypical presentation with therapeutic challenge

Lipodystrophy is regarded as a functional disturbance of the hypothalamus. Typically, face is the first part to be affected, and its aspect in an advanced case is characteristic: hollowed temples, prominent zygomatic bones, and sunken cheeks. When the patient smiles, numerous wrinkles appear in the cheeks, giving the appearance of premature senility. Here is a report of a rare case of partial lipodystrophy with an atypical presentation which had alarmingly affected the patient's appearance. Our main purpose of presenting this rare case in oral medicine is an attempt to educate oral physicians about lipodystrophy and increase awareness about the presence of subtle forms that may be underdiagnosed.

Rabson-Mendenhall syndrome

Rabson-Mendenhall syndrome is a rare, autosomal recessive disorder affecting insulin receptor. This disorder is characterized by insulin-resistant diabetes mellitus, hyperinsulinemia, deficiency of subcutaneous fat, acanthosis nigrican, growth retardation, coarse and senile appearance, precocious puberty, and dental prematurity, enlarged genitalia, and pineal hyperplasia. Mutations of the insulin receptor gene affecting insulin action appear to be the basic mechanism underlying this syndrome. Herein, we present a case report on Rabson-Mendenhall syndrome in a 9-year-old girl.

Obowiązki i przywileje ludzi starszych według Klemensa Aleksandryjskiego

In an old man, Clement of Alexandria sees the ideal of a perfect Christian, who thanks to intellectual and moral formation, reached the status of God’s friend. For this reason, he is entitled to the care of his family, to be honored and respected by the young people, to drink a wine and conduct conversations during the feasts and to undertake the functions of the teacher and housemaster. The old man is required to maintain a senile appearance without cosmetic procedures and to hold tactful conversations and to drink a wine in moderation during the feasts.

Cardiovascular Complications of Cutis Laxa Syndrome

Cutis laxa syndrome is a rare inherited connective tissue disorder characterized by inelastic loose hanging skin, which gives the appearance of premature aging. Histology shows degenerative changes in the elastic fibers of the connective tissue throughout the body. Severe aortic dilatation may occur because of medial elastic fiber degeneration. We report the case of a 27-year-old man with a confirmed diagnosis of cutis laxa syndrome. The patient, of Albanian ethnic origin, had no family history of the disease and no consanguinity between parents. All siblings, 4 brothers and 3 sisters, are well and free of disease. He was asymptomatic, but because of his loose facial skin and senile appearance (Figure 1), he consulted a dermatologist concerning having plastic surgery on his face, which he subsequently had performed. The dermatologist suspected cutis laxa and referred him for a full assessment of his condition. Figure 1. Physical appearance of the patient. Aged appearance with wrinkly skin on the dorsal aspect of the arms ( A ), neck ( B ), and back ( C ). His ECG showed sinus rhythm with no rhythm or conduction disturbance. Chest x-ray (Figure 2A) showed abnormalities …

Cutis laxa acquisita associated with cutaneous mastocytosis

A female child, a product of a nonconsanguineous parentage and normal pregnancy, was seen first at the age of 4 years. She had suffered from recurrent episodes of multiple, erythematous, confluent plaques and a few bullous lesions all over the body since infancy. The child was irritable but had no history of flushing, dyspnea, wheezing, or frequent diarrhea. Darier's sign was strongly positive and systemic examination did not reveal any abnormality. Routine laboratory investigations were normal and a skin biopsy specimen revealed an unremarkable epidermis and dense proliferation of round to spindle‐shaped mast cells which stained positive for metachromatic granules (Fig. 1). With the diagnosis of urticaria pigmentosa, she was managed with antihistaminic drugs and the parents were advised to handle the child gently. She did not report for further follow‐up.Photomicrograph of skin histology showing metachromatic granules (toluidine blue, ×40)imageRecently, the child, now 8 years of age, was brought again with finely wrinkled, lax, and redundant skin, especially of the face, giving her a senile appearance (Fig. 2). Systemic examination did not show any abnormality. History revealed that the child had been asymptomatic during the last 4 years even without treatment, but developed slowly progressive lax and pendulous skin. A repeat biopsy from the lax facial skin revealed sparse and fragmented elastic fibres, normal collagen, and a perivascular and intradermal cellular infiltrate composed of metachromatic mast cells. Her serum α1‐antitrypsin levels were 190.0 mg/dL (normal, 93–224 mg/dL) and a pulmonary function test showed no abnormality. Treatment with antihistaminic drugs was started again and she was advised to have a cosmetic facial uplift at a later stage.Patient with urticaria pigmentosa seen at 8 years of age showing cutis laxa and a senile appearanceimage

Severe Form of Cockayne Syndrome With Varying Clinical Presentation and No Photosensitivity in a Family

We report six patients with Cockayne syndrome type B without photosensitivity. The patients are from the same inbred family and exhibit variable clinical features. The main clinical manifestations were progressive encephalopathy including intracranial calcification and white-matter lesions, dwarfism without growth hormone deficiency, senile appearance, mental and motor retardation, atrophy of subcutaneous fat tissue, severe pectus carinatus, and spasticity. Clinical photosensitivity was not observed in any patient. Other clinical findings were cataract, pigmentary retinopathy, and peripheral neuropathy. The onset of the disease was between 3 and 6 months of age. Molecular genetic analyses in the family established linkage to ERCC6, the gene responsible for Cockayne syndrome type B, confirming the clinical diagnosis.

Mutation in the CSB gene in a patient with Cerebro-Oculo-Facio-Skeletal syndrome

Cerebro-Oculo-Facio-Skeletal (COFS) syndrome is an autosomal recessive multiple malformation syndrome with congenital microcephaly, microphthalmia and cataracts, characteristic facial features, camptodactyly and rocker-bottom feet. Survival is usually less than 5 years. Cockayne syndrome is an autosomal recessive condition with dwarfism, precocious senile appearance, eye abnormalities and mental retardation. Features are usually not apparent until 2-4 years of age. Two complementation groups have been identified (CS-A and CS-B) and both genes have been characterized. There is an early onset form of Cockayne syndrome (EOCS) and it has been suggested that EOCS and COFS may be the same condition. Recently a mutation in the CSB gene has been reported in two related patients with the COFS phenotype.We describe a patient with congenital microcephaly, microphthalmia, prominent nose, micrognathia, large ears, small mouth with upper lip overlapping lower lip, joint contractures, rockerbottom feet, congenital cataracts, and profound growth and developmental retardation. At age 2 years 10 months she developed seizures, proteinuria, and acute renal failure and died. The family history is notable for a female sibling with identical clinical features who died at age 3 of nephrotic syndrome. There is no reported consanguinity. DNA sequence analysis of the CSB gene in fibroblasts from this patient revealed a homozygous 177 bp deletion in exon 10.This is a different mutation than that previously reported in COFS syndrome and provides further evidence that COFS syndrome is caused by mutations in the CSB gene. Patients identified with the COFS phenotype should have UV sensitivity studies and analysis of the CSB gene; identification of a mutation would provide a method for prenatal diagnosis in subsequent pregnancies and for carrier testing.

Cockayne syndrome in two brothers

We report the clinical history of two brothers with the classical Cockayne syndrome. The main manifestations consisted of cachectic dwarfism, mental retardation, intracranial calcifications, microcephaly, enophthalmos, senile appearance, joint hypomotility and skin photosensitivity. In one of these children, who died at 10 years of age of bronchopneumonia, necropsy studies revealed a variety of anomalies, mainly encephalic,which included an arachnoidal cyst at the base of the cerebellum, a defect apparently previously undescribed inpatients with this syndrome.

Cutis Laxa (Generalized Elastolysis) A Report of Four Cases with Autopsy Findings

Four children with cutis laxa (generalized elastolysis) are reported. The first three cases were siblings from a Canadian Indian family and the fourth case was the only affected child in an American Black family. Loose and sagging skin folded over the face, neck and trunk, gave a premature senile appearance. Post-mortem examination was performed on the first three cases. The most common and serious visceral involvement was development of pulmonary emphysema. This was present in two autopsied cases and was demonstrated by chest X-ray in the fourth case. Other abnormalities included large inguinal and perineal hernia, rectal diverticulum and multiple diverticulae of the urinary bladder.

Letter: Progeria: a possible therapeutic approach.

To Editor.— An editorial by Samuel Vaisrub (226:1565, 1973) under title Nature's Experiment in Unnatural Aging, discussed possibility of learning from one of nature's mistakes how to retard aging process. He pointed out that progeria, a disease inherited as an autosomal recessive trait, is characterized by precocious senility, and that the afflicted child with his wizened face, dwarfed stature, and general appearance of senility usually dies of coronary heart disease during first or second decade of life. Further evidence of senility has been established by finding deposits of lipofuscin, age in various cells of body, and by incidence of focal fibrosis of myocardium. This pigment, according to Tappel1and other investigators, results from destructive autooxidation (lipid peroxidation) of lipid portion of biological membranes of cells and intracellular organelles. It is believed to represent an important factor

Nature's Experiment in Unnatural Aging

A rare, inborn error of metabolism is frequently referred to as nature's experiment. By adding experimental touches of his own, the investigator may gain insights not only into the mechanisms of a particular genetic disorder, but also into related physiologic derangements underlying other, more common conditions. We owe much of our knowledge of physiology and pathophysiology to studies of genetic rarities. One such genetic disease is progeria . Inherited as an autosomal recessive trait, this disease is characterized by precocious senility. The afflicted child with his wizened face, dwarfed stature, and the general appearance of senility usually dies of coronary heart disease during the first or second decade of life. The stamp of senescence is imprinted in various cells by deposits of lipofuchsin, and in the myocardium by focal fibrosis. Can this disorder, which telescopes a life-span into the brief period of a dozen or so years, shed some light on

Rhytidectomy and related procedures designed to correct the causes of the appearance of facial senility

Rhytidectomy and related procedures designed to correct the causes of the appearance of facial senility

Werner's syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process.

Werner’s syndrome was first described in 1904 by Otto Werner in his doctoral thesis, “Uber Katarakt in Verbindung mit Sklerodermie” (“Cataract in combination with scleroderma”) (137). He reported four sibs with similar clinical findings: shortness of stature; senile appearance; graying of the hair beginning at about age 20; cataracts appearing during the third decade; skin changes (tautness, atrophy, hyperkeratoses and ulceration) designated as scleroderma and primarily involving the feet and, to a lesser degree, the hands; joint deformities associated with the skin abnormalities; atrophy of the muscles and connective tissues of the extremities; and early cessation of menstruation. Werner was impressed principally by the cataracts, skin changes, senile appearance, and graying of the hair and attributed the condition to a “failure” of the cells derived from the ectoderma. Although he knew that the features displayed by the affected members of the family represented a new and distinct entity, he related this condition to one described by Rothmund (106) in which juvenile cataracts were found together with skin changes. The implied association of these two syndromes and the identification of the skin alterations in Werner’s cases as scleroderma were sources of confusion for many years, and it was not until the appearance of the paper by Oppenheimer and Kugel in 1934 (94) and of the comprehensive study by Thannhauser in 1945 (131) that the two syndromes were clearly delineated and the character of the skin changes defined.

Some potential areas for research on means of drastically increasing the human life span

In principle there are two different methods of extending the life span. The first consists of the removal of factors leading to premature ageing and includes various social improvements, control of disease, and conditions of work and living, etc. The second method is directed towards an alteration in the rate of biological ageing processes and may be expected to increase the life span of humans by two or three times above its present natural limits (80 to 100 years). At the present time, as the conditions for living into old age are considerably improved in many countries, two other problems face us. These are: (1) to increase drastically the life span of people who have not yet reached old age by postponing the appearance of senility; and (2) to extend the life span of older persons by rejuvenating them. The method by which these effects may be achieved is through an interference in the biology of the ageing process. In discussing the main possible directions which such an interference in the ageing process might take the author considers that longevity is determined primarily by the level of disparity in some links of biochemical reactions between the amount of substances coming into the reactions and the amount of substances entering the consequent links of biochemical reactions. In the present discussion we will treat four methods of searching for means of effecting an increase in length of life.

Progeria, a pathologic study

S I N c e . Gilford 1 introduced the term progeria in 1904 fewer than 30 typical cases have been reported. A thorough review of the literature with full description of the syndrome has been made by Thomson and Forfar in 19502 and by Gabr in 19547 Several cases have been described subsequently. 4-~~ The syndrome is characterized by stunted growth associated with an appearance of premature senility and a normal mentality (the old wizened dwarf). The disease first manifests itself at the end of the first year of life by causing an arrest of growth in both weight and in height, loss of hair, loss of subcutaneous fat with subsequent wasting, and relative enlargement of the joints with limitation of their movement. The face appears small with a receding chin, overcrowded teeth, and prominent eyes with no eyelashes or eyebrows. The skin is thin and the nails are atrophied; the hands with their flexed fingers and enlarged joints simulate the hands of an old person. Skeletal .changes, which include thin bones, small clavicles, defective ossification of the skull, and coxa valga, are often present. As the child grows older arteriosclerotic changes develop, and the patient usually dies in the second decade

Hereditary premature senescence of the rabbit. II. Acute form; general features.

The acute form of hereditary premature senescence in 79 rabbits, among which the 20th generation of the condition was represented, has been described. The manifestations did not differ in kind from those previously described in connection with the chronic form (1) of the complex but their degree and, in particular, the severity and the rate of progression of systemic degeneration were much greater. The rabbits either did not survive to 2 years 6 months, of age or their physical condition had become critical by this time. A senile appearance, largely due to deteriorative changes of the coat, was frequently observed. The essential nature of the senescence condition was obviously a degeneration and one in which vital mechanisms essential to the maintenance of health were involved.

ENDOCRINE FACTORS IN UNDERNUTRITION1

IN 1874 SIR WILLIAM GULL (1) described two young women in whom anorexia led to starvation and “depression of all vital functions,“ with bradycardia, amenorrhea, and the appearance of ageing. Recovery occurred when the caloric intake was increased. Since Gull called attention to this syndrome, many other cases of so-called anorexia nervosa have been described. In 1930 Berkman (2) reported 117 cases which had been observed at the Mayo Clinic between 1917 and 1929. In 1936 Ryle (3) reported 51 cases. The syndrome, observed most frequently in young women, is characterised by anorexia, usually associated with psychic disturbances, and followed by marked weight loss, hypotension, bradycardia, subnormal temperature, lowered basal metabolic rate, atrophy of the genitalia, amenorrhea, hypoglycemia, increased glucose tolerance, and occasionally loss of hair and the appearance of senility. During recent years the similarity of this clinical syndrome to that of hypophyseal cachexia (Simmonds-disease) has been the sub...