Oral manifestations and craniofacial characteristics of hutchinson-gilford progeria syndrome: a case report

Introduction: Hutchinson-Guilford progeria syndrome (HGPS) is a rare genetic disease with a characteristic phenotype of premature aging in young children caused by a mutation in the LMNA gene and consequent accumulation of progerinin the cell. Aim: Describe oral manifestations of Hutchinson-Guilford progeria syndrome. Case Report: This is a case report of a six-year-old female patient with Hutchinson-Guilford Progeria syndrome. The physical examination revealed skin atrophy, lipodystrophy, hair rarefaction, prominent blood vessels of the scalp, craniofacial disproportion, perioral cyanosis and enlarged knee joints. The intraoral exam revealed limited mouth opening, mixed dentition with normal tooth anatomy and anteroinferior crowding. The eruption sequence and chronology were abnormal. The treatment plan included professional prophylaxis, the topical application of fluoride as well as both oral hygiene and dietary counselling. Monitoring the development of dentition and an early and timely dental intervention contributed to the maintenance of child's oral health. Conclusion: Early clinical and educational interventions can help patients with HGPS maintain adequate oral health status and improve their quality of life.

Introdução: A Progéria ou Síndrome de Hutchinson-Guilford (HGPS) é uma doença genética rara com um fenótipo característico de envelhecimento precoce em crianças pequenas, causado por uma mutação no gene LMNA e conseqüente acúmulo de progerina na célula. Objetivo: Descrever as manifestações orais da Síndrome de Hutchinson-Guilford. Relato do Caso: Este é um relato de caso de uma paciente de seis anos com Síndrome de Hutchinson-Guilford. O exame físico revelou atrofia da pele, lipodistrofia, rarefação dos cabelos, vasos sangüíneos proeminentes no couro cabeludo, desproporção craniofacial, cianose perioral e aumento das articulações dos joelhos. O exame intraoral revelou abertura bucal limitada, dentição mista com anatomia dentária normal e apinhamento ântero-inferior. A sequência e a cronologia de erupção estavam alteradas. O plano de tratamento incluiu profilaxia profissional, aplicação tópica de flúor, bem como orientação de higiene bucal e aconselhamento dietético. O acompanhamento do desenvolvimento da dentição e a intervenção odontológica precoce e oportuna colaboraram com a manutenção da saúde bucal da criança. Conclusão: Intervenções clínicas e educacionais precoces podem ajudar os pacientes com HGPS a manter um estado de saúde bucal adequado e melhorar sua qualidade de vida.

Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.

Differential stem cell aging kinetics in Hutchinson-Gilford progeria syndrome and Werner syndrome

Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome (WS) are two of the best characterized human progeroid syndromes. HGPS is caused by a point mutation in lamin A (LMNA) gene, resulting in the production of a truncated protein product-progerin. WS is caused by mutations in WRN gene, encoding a loss-of-function RecQ DNA helicase. Here, by gene editing we created isogenic human embryonic stem cells (ESCs) with heterozygous (G608G/+) or homozygous (G608G/G608G) LMNA mutation and biallelic WRN knockout, for modeling HGPS and WS pathogenesis, respectively. While ESCs and endothelial cells (ECs) did not present any features of premature senescence, HGPS- and WS-mesenchymal stem cells (MSCs) showed aging-associated phenotypes with different kinetics. WS-MSCs had early-onset mild premature aging phenotypes while HGPS-MSCs exhibited late-onset acute premature aging characterisitcs. Taken together, our study compares and contrasts the distinct pathologies underpinning the two premature aging disorders, and provides reliable stem-cell based models to identify new therapeutic strategies for pathological and physiological aging.

Progeria of the Heart in Type 1 Diabetic Children?

No abstract available.

Analysis of a case with typical Hutchinson-Gilford progeria syndrome with scleroderma-like skin changes and review of literature / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore clinical, radiographical and genetic characteristics of classical Hutchinson-Gilford progeria syndrome (HGPS).</p><p><b>METHOD</b>Data of a case of HGPS diagnosed at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology was analyzed and related literature was reviewed.</p><p><b>RESULT</b>At the age of 8 months, the affected-infant presented with characteristic manifestation such as short stature, low weight, frontal bossing, alopecia, prominent scalp veins, micrognathia with a vertical midline groove in the chin, sclerodermatous skin, knee joints contracture with a horse-riding stance, and limited range of movement of ankle joints. Blood test showed blood platelet count (416-490) ×10(9)/L. Lower extremities MRI showed reduced subcutaneous fat. LMNA gene analysis showed that the affected-infant carried typical heterozygous mutation: c. 1824C>T (p. G608G), while his parents were normal. At the age of 13 months, X-rays showed short distal phalanges and clavicles with acro-osteolysis. After following up for 15 months, his appearance of progeria became more apparent. As far as we know, there are only 2 cases of classical HGPS confirmed by gene analysis in China.</p><p><b>CONCLUSION</b>Classical HGPS should be considered when infants appeared with sclerodermatous skin. Genetic analysis could help to diagnose classical HGPS as early as possible and avoid unnecessary investigations. In addition, affected-infants need to be long term followed-up and provided genetic counseling.</p>

Arterial Ageing

Arterial ageing is characterized by age associated degeneration and sclerosis of the media layer of the large arteries. However, besides ageing, clinical conditions, which enhance oxidative stress and inflammation act to accelerate the degree of arterial ageing. In this review, we summarized the pathophysiology and contributing factors that accelerate arterial ageing. Among them, we focused on hypertension, the renin-angiotensin-aldosterone system and vascular inflammation which are modifiable causes of the arterial ageing process. Also, novel treatment targets derived from the disease models such as the Hutchinson Gilford Progeria Syndrome were reviewed.

Enfermedades hereditarias de la dermis: revisión de la literatura / Hereditary diseases of the dermis: literature review

Nuestra piel tiene propiedades de elasticidad y firmeza, dada por las fibras del tejido conectivo ubicadas en la dermis. La elasticidad está dada principalmente por pequeñas fibraselásticas compuestas de elastina, mientras que la firmeza se explica por las redes de fibrillas de colágeno tipo I, III y V. La relevancia de estos componentes de la matriz extracelular, junto con otras fibras, como fibrilina y fibulina, se ha reflejado en el reconocimiento de diferentes enfermedades hereditarias causadas por mutaciones en estas proteínas. Muchas de éstas pueden tener características comunes, constituyendo un espectro de alteraciones, dependiendo de la proteína alterada, dando un pronóstico particular tanto en morbilidad y mortalidad. En esta revisión se desarrollarán las principales patologías de la dermis de importancia en dermatología.

Our skin is flexible and firm due to the fibers of the connective tissue in the dermis. Flexibility is mainly given by little elastic elastine fibers, meanwhile firmness is expressed by fibers networks made of collagen type I, III and V. The importance given to these components, including other fibers like fibrillin and fibulin in the extracellular matrix has been displayed in the recognition of different hereditary diseases caused by mutations in these proteins. Many of them have common characteristics, that build a wide spectrum of disorders depending on the altered protein, and give a particular prognostic in morbidity as well as in mortality. The main pathologies of the dermis with an importance in dermatology will be considered in this review.

Estudio del envejecimiento con un modelo celular del síndrome de progeria de Hutchinson-Gilford / Study of the agening with a cellular model of Hutchinson-Gilford progeria syndrome

Se presenta en forma resumida los principales hallazgos del trabajo de Liu y col (1), investigadores del Instituto Salk, California, publicado en abril de 2011, donde se describe un modelo celular in vitro del síndrome de progeria de Hutchison-Gilford (SPHG), basado en células madre pluripotentes inducidas po reprogramación de fibroblastos. Tiene gran interés porque ofrece la posibilidad de estudiar la fisiopatología de las enfermedades que cursan con envejecimiento rápido, prematuro y ayudar a compreder mejor los procesos de envejecimiento que ocurren en la población humana general. Se incluye información básica relacionada con la progeria

A summary of the main findings published in April 2011 by Liu et al (1), researchers at the Salk Institute, California, where a cellular in vitro model of Hutchinson-Gilford progeria syndrome (HGPS) was described based on induced pluripotent stem cells derived from reprogrammed fibroblasts. It is of great interest because it allows the study of the pathogenesis of premature, rapid aging and helps understand ageing of the general human population. Basic information about progeria is included

Ocular manifestations in the Hutchinson-Gilford progeria syndrome.

The Hutchinson-Gilford progeria (HGP) syndrome is an extremely rare genetic condition characterized by an appearance of accelerated aging in children. The word progeria is derived from the Greek word progeros meaning ‘prematurely old’. It is caused by de novo dominant mutation in the LMNA gene (gene map locus 1q21.2) and characterized by growth retardation and accelerated degenerative changes of the skin, musculoskeletal and cardiovascular systems. The most common ocular manifestations are prominent eyes, loss of eyebrows and eyelashes, and lagophthalmos. In the present case some additional ocular features such as horizontal narrowing of palpebral fissure, superior sulcus deformity, upper lid retraction, upper lid lag in down gaze, poor pupillary dilatation, were noted. In this case report, a 15-year-old Indian boy with some additional ocular manifestations of the HGP syndrome is described.

Hutchinson-Gilford Progeria Syndrome with G608G LMNA Mutation

Hutchinson-Gilford progeria syndrome (HGPS) is a rare condition originally described by Hutchinson in 1886. Death result from cardiac complications in the majority of cases and usually occurs at average age of thirteen years. A 4-yr old boy had typical clinical findings such as short stature, craniofacial disproportion, alopecia, prominent scalp veins and sclerodermatous skin. This abnormal appearance began at age of 1 yr. On serological and hormonal evaluation, all values are within normal range. He was neurologically intact with motor and mental development. An echocardiogram showed calcification of aortic and mitral valves. Hypertrophy of internal layer at internal carotid artery suggesting atherosclerosis was found by carotid doppler sonography. He is on low dose aspirin to prevent thromboembolic episodes and on regular follow up. Gene study showed typical G608G (GGC- > GGT) point mutation at exon 11 in LMNA gene. This is a rare case of Hutchinson-Gilford progeria syndrome confirmed by genetic analysis in Korea.

Werner syndrome: a case report and review of literature

Werner's syndrome is a rare inherited disorder characterized by short stature, sclerosed skin, cataract and premature aging of the face. The disease involves multiple systems of the body and some of the abnormalities may cause life threatening complications such as myocardial infarction and malignancy. We report a case of this rare disorder

Progeria.

Hutchinson Gilford Progeria Syndrome (HGPS) is a rare, sporadic, autosomal dominant syndrome that involves premature ageing and death at early age due to myocardial infarction or stroke. A 30-year-old male with clinical and radiologic features highly suggestive of HGPS is presented here with description of differential diagnosis, dental considerations and review of literature.

[Progeria syndrome with congenital livedo reticularis lesion: a case report]

Progeria syndrome is a very rare genetic disorder with and incidence of 1 in 8 million live births that is probably due to autosomal dominant mutation. Clinical presentations show features of premature aging, growth failure, characteristic face, alopecia, loss of subcutaneous fat and stiffness of a joint that all become apparent during the 2nd year of life. The aim of this case report is presenting a rare congenital livedo reticularis case and reviewing the signs and symptoms of this patient. Patients was a 15-month-old male infant diagnosed with growth failure: 4.9 kg weight, 63 cm and 48 cm head circumference who was admitted because of failure to thrive. The patient was outcome of a full-term pregnancy with no problems in parents except for livedo reticularis. The patient's facial appearance reminded of fledgling bird with a small face, very sparse scalp hair, absent eyelash and eyebrow, micrognathia, thin lips, prominent ears and absence of an ear lobule. Physical examination of skin revealed dryness, being shiny, mild tautness, loss of the subcutaneous fat and livedo reticularis lesions. Based on clinical finding and paraclinical evaluations, the case was diagnosed with Hutchinson-Gilford or Progeria syndrome. This study showed that careful history taking and exact physical examination of the patients led to the diagnosis of a rare syndrome and finding new signs as well. The important finding here was the presence of congenital livedo reticularis along with progeria syndrome which had not been reported previously in the literature

Síndrome de Werner associada a quadro esclerodermiforme: relato de caso e revisão da literatura / Werner's syndrome associated with scleroderma-like syndrome: case report and literature revision

A síndrome de Werner é uma doença autossômica recessiva rara associada a envelhecimento precoce, cujo quadro cutâneo deve ser distinguido daquele encontrado na esclerose sistêmica (ES). Descrevemos aqui o caso de uma paciente de 39 anos de idade, portadora de síndrome de Werner, encaminhada ao nosso serviço com hipótese diagnóstica inicial de ES. A paciente apresentava várias manifestações associadas à síndrome de Werner, incluindo cabelos precocemente grisalhos, voz estridente, baixa estatura, alterações cutâneas esclerodermiformes, diabetes melito, catarata, hipogonadismo, hipotireoidismo e hiperlipidemia. Não apresentava fenômeno de Raynaud, manifestações viscerais típicas da ES, alterações capilaroscópicas periungueais ou auto-anticorpos. O diagnóstico de síndrome de Werner, apesar de raro, deve ser lembrado no diagnóstico diferencial de ES, principalmente na presença de manifestações atípicas e na ausência de alterações típicas da ES.

Werner's syndrome is a rare autosomal recessive disease associated with premature ageing. Skin alteration must be distinguished from cutaneous manifestation of systemic sclerosis (SSc). We describe a case of a 39 years old patient with Werner's syndrome admitted with an initial diagnostic hypothesis of SSc. The patient had many characteristic features associated with Werner's syndrome including gray hair, hoarseness, short stature, scleroderma-like skin changes, diabetes mellitus, cataracts, hypogonadism, hypothyroidism, and hyperlipidemia. There was no Raynaud's phenomenon, other typical visceral manifestation of SSc, nailfold capillary alterations or autoantibodies. Werner's syndrome diagnosis notwithstanding rare, should be remember in the differential diagnosis of SSc, mainly in the presence of atypical manifestations and in the absence of typical features of SSc.

case of acrogeria - a rare premature ageing syndrome

A case of acrogeria of a 9-month-old boy is reported here who presented with dry, scaly skin, birdlike facies, prominent frontal tuberosities, recessed chin, dry, thin skin with generalized subcutaneous fat loss, prominent veins, prominent eyes, thin and brittle nails, poorly developed musculature and hair loss at the back of scalp

Progeria-First case report from Pakistan

Progeria is characterized by premature aging and the clinical manifestations part of the well known Hutchinson-Gilford syndrome. We present the first known case of Progeria in Pakistan

Progeria: presentación de un caso / Progeria: a case report

Se realizó la presentación de un transicional de 2 años de edad con Síndrome de Hutchinson, Gilford o Progeria, se relaciona la evaluación clínico radiológica del caso, dada su escasa frecuencia y se efectua una revisión del tema que abarcó criterios diagnósticos, manifestaciones más frecuentes y tratamientos más utilizados en el control de la enfermedad. Se analizan exámenes de laboratorio, clínicos y radiológicos, siendo este último pilar fundamental en el diagnóstico de esta patología donde se evidenciaron hallazgos característicos del síndrome, en especial vértebras en fischmoutch, persistencia de la fontanela anterior y suturas, así como engrosamiento de partes blandas de rodillas con epífisis distal del fémur en trompeta, unidos a las dismorfias del infante. La Progeria lleva a un rápido envejecimiento del niño, tienen un deficiente crecimiento durante su primer año de vida, son pequeños y delgados. El escaso número de pacientes reportados en el mundo y el fallecimiento de estos casi siempre en la segunda década de la vida hace limitado el conocimiento de esta enfermedad.

The transitional case of a two year old child the Hutchinson-Gilford Syndrome or Progeria was presented.The clinico-radiological evaluation was correlated. Given its low frequency, a review of such theme, which comprised diagnoses, most frequent manifestations and therapies instituted was done.The clinico-radiologic investigation as well as lab tests were done, being radiology the major pillar in the diagnosis of this pathology whereby characteristic findings of this syndrome were evident such as : Fishmouth vertebrae, persistent anterior fontanelle of the skull and sutures as well as thickening of soft tissues of the knee with distal epiphysis of the trumpet-like femur, in conjunction with the dysmorfias of the patient. Progeria leads to a fast aging of the child. It shows a defficient growth during the first year of age,being short and thin.The little number of pts reported in the World and the disease of them almost always during the second decade of their lives makes the knowledge of this disease limited.

[Progeroid syndrome and mutation in LMNA gene: report of two cases from Iran]

Two Iranian cases with very rare progeroid syndrome are reported. The first is a 24-year-old girl who has been healthy till her 13[th] birthday. From that time she has been suffering from a progressive generalized and multi-systemic illness. The cardinal clinical findings were growth retardation, subcutaneous fat loss, skin dryness and wrinkling, scattered focal sclerodermoid-like changes, prominence of superficial vessels, gradual loss of scalp hair and eyebrows and cardiac involvement in the form of dilated cardiomyopathy. All the above findings were suggestive of precocious ageing and the clinical diagnosis of Werner syndrome. The second case is a 6-year-old boy with typical clinical findings of Progeria or Hutchinson-Gilford syndrome. The diagnoses were confirmed by molecular analysis of the samples in Washington and Marseille. In the first case there was no molecular abnormality in Werner's gene[WRN], but there was a mutation in the LMNA gene. The mutation was substitution of C to G in codon number 57, and the codon GCA [alanine] changed to CCA [proline]. So, in the codon 57 of the protein Lamin A/C proline had replaced alanine [A57>P]. The mutation in the second case [Progeria=Hutchinson-Gilford syn.] was a point mutation at the exon 11 of Lamin A/C protein resulting in the replacement of thymine by cytosine in the nucleotide number 1824[1824C>T]. The importance of lamins and the mechanism and pathogenesis of progeroid syndromes are discussed briefly