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CASE REPORT
Year : 2014  |  Volume : 5  |  Issue : 4  |  Page : 478-481  

Hutchinson - Gilford progeria syndrome: A rare case report


Department of Dermatology, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India

Date of Web Publication10-Oct-2014

Correspondence Address:
Subhash Kashyap
Department of Dermatology, Indira Gandhi Medical College, Shimla, Himachal Pradesh - 171 001
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2229-5178.142507

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   Abstract 

Hutchinson - Gilford Progeria Syndrome is a rare genetic disorder characterized by premature aging involving the skin, bones, heart, and blood vessels. We report a three-year-old boy with clinical manifestations characteristic of this syndrome. He had a characteristic "plucked-bird" appearance, prominent eyes and scalp veins, senile look, loss of scalp hair, eyebrows, and eyelashes, stunted growth, and mottled pigmentation with sclerodermatous changes over the trunk and lower limbs. Radiological changes and decreased high-density lipoprotein (HDL) levels were also characteristic of the syndrome. This interesting case is reported for its rarity.

Keywords: Hutchinson - Gilford syndrome, premature aging, progeria


How to cite this article:
Kashyap S, Shanker V, Sharma N. Hutchinson - Gilford progeria syndrome: A rare case report . Indian Dermatol Online J 2014;5:478-81

How to cite this URL:
Kashyap S, Shanker V, Sharma N. Hutchinson - Gilford progeria syndrome: A rare case report . Indian Dermatol Online J [serial online] 2014 [cited 2019 Dec 5];5:478-81. Available from: http://www.idoj.in/text.asp?2014/5/4/478/142507


   Introduction Top


Hutchinson - Gilford Progeria Syndrome (HGPS; MIM 176670) was first described in 1886 by Jonathan Hutchinson and by Hastings Gilford in 1897. [1] Since then, just over 100 cases of HGPS have been reported and currently, there are approximately 40 known cases worldwide. [2] Most cases occur due to de novo mutation and are rarely inherited. Sporadic autosomal dominant mutation in LMNA genes is responsible in most cases. [3] These patients exhibit characteristic facies; so, they look alike. The appearance is described as a "plucked-bird" appearance. [4] Significant morbidity and mortality result from accelerated atherosclerosis of the carotid and coronary arteries leading to premature death during the second decade of life. [5]


   Case report Top


A three-year-old boy presented with progressive loss of scalp hair, eyebrows, and eyelashes since six months of age along with stunted growth as a major complaint. The child's antenatal history was normal but was born to third-degree consanguineously married parents. On examination, he had a senile look with prominent eyes, sparse hair with patches of alopecia and visible veins over the scalp, beaked nose, and receded chin [Figure 1]. His voice was high pitched and growth was stunted as parameters were less than the third percentile. Teeth and genitals were normal and intelligence quotient (IQ) was corresponding to the age. Hands were short and clawed with thickening and hardening of the skin over the knuckles with racquet nails. The ribs were prominent and anterior fontanelle was open. There was mottled pigmentation and sclerodermatous changes over the trunk and lower limbs [Figure 2]. Lower limbs also had prominence of knees and slight valgus deformity [Figure 3] and [Figure 4].
Figure 1: Typical facies of progeria: Senile look with prominent eyes, sparse hair, beaked nose, and receded chin

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Figure 2: Mottled pigmentation and sclerodermatous changes over the trunk

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Figure 3: Skin tightening and prominence of knees

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Figure 4: Mid fl exion and slight valgus deformity of lower limbs leading to a "horse-riding stance"

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Routine investigations were within normal limits. The serum lipid profile showed a decrease in high-density lipoproteins (HDL). X-ray of the chest showed a pyriform thorax, overcrowding of proximal ribs, and short clavicle with pointed lateral ends [Figure 5]. X-ray of the skull showed diastasis of the sutures and prognathism [Figure 6]. X-rays of hands and feet showed acro-osteolysis of phalanges and tarsals [Figure 7].
Figure 5: X-ray of the chest showing a pyriform thorax, overcrowding of proximal ribs, and short clavicle with pointed lateral ends

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Figure 6: X-ray of the skull showing diastasis of the sutures and prognathism.

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Figure 7: X-ray of the feet showing acro-osteolysis of tarsals

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   Discussion Top


Most cases of HGPS occur due to de novo autosomal dominant mutation in the LMNA gene, located on band 1q21.1-1q21.3. [2] Rarely, transmission can be autosomal recessive or maternal due to gonadal mosaicism. Most commonly, there is transitional mutation replacing cytosine with thymine. This leads to abnormal transcription of the nuclear lamina structural protein called prelamin A. Normal farnesylation of prelamin A allows it to attach to the nuclear membrane. Failure to remove this farnesyl group, due to the mutation, permanently affixes the protein to the nuclear membrane [Table 1]. This affects nuclear morphology and integrity, deoxyribonucleic acid (DNA) repair, regulation of gene expression, and telomere stability. Ultimately, there is genomic instability, decreased cell proliferation, and premature cell senescence and death. [6]
Table 1: Difference in prelamin a formation in normal and mutated LMNA gene

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The infant is generally healthy at birth but there may be sclerodermatous skin changes involving the trunk and extremities in some cases. Manifestations appear within one to two years in most of the cases. [7] Hair growth decreases over the scalp and other parts of the body with areas of alopecia followed by cardiovascular involvement. IQ remains normal. [8] Lipodystrophy involving the face leads to typical facies with senile look, glyphic nose, and "plucked bird" appearance. Involvement of the lower limbs with valgus deformity and mid flexion leads to a "horse riding" stance. [9]

Radiography changes manifest within the second year of life. There is diffuse osteopenia, acro-osteolysis of the phalanges and distal clavicles, but bone age is normal. Hyaluronic acid excretion is increased from fibroblasts and there is extensive lipofuscin deposition. [10]

HGPS is considered a segmental progeroid syndrome in the sense that it does not recapitulate all the characteristic phenomena of aging like increased tumor formation and cataract development. Hypertension develops, but unlike arteriosclerosis in the general population, in progeria, the only lipid abnormality is decreased HDL levels. [10]

This syndrome should be distinguished from scleroderma, Cockayne syndrome, Rothmund - Thomson syndrome, Werner syndrome, acrogeria, and anhidrotic ectodermal dysplasia. In our case, Cockayne syndrome was ruled out because of lack of photosensitivity, facial erythema, and ocular defects, and normal IQ. Rothmund - Thomson syndrome was ruled out by the absence of erythema, poikiloderma, and cataract. Earlier age of onset ruled out Werner syndrome. Acrogeria also manifests at birth but involves only extremities with no tendency to atheroma or decreased life expectancy. There was an absence of conical teeth, hypotrichosis, and partial or complete anhidrosis, which ruled out hypohidrotic ectodermal dysplasia.

Typical clinical features of the child were sufficient to make the diagnosis. Decreased HDL levels and typical X-ray findings confirmed the diagnosis.

This case is reported for its rarity.

 
   References Top

1.
Hutchinson J. Case of congenital absence of hair, with atrophic condition of the skin and its appendages, in a boy whose mother had been almost wholly bald from alopecia areata from the age of six. Lancet 1886;1:923.  Back to cited text no. 1
    
2.
Pollex RL, Hegele RA. Hutchinson - Gilford progeria syndrome. Clin Genet 2004;66:375-81.  Back to cited text no. 2
    
3.
Brown WT. Human mutations affecting aging - a review. Mech Ageing Dev 1979;9:325-36.  Back to cited text no. 3
[PUBMED]    
4.
Gordon CM, Gordon LB, Snyder BD, Nazarian A, Quinn N, Huh S, et al. Hutchinson-Gilford progeria is a skeletal dysplasia. J Bone Miner Res 2011;26:1670-9.  Back to cited text no. 4
    
5.
Stehbens WE, Wakefield SJ, Gilbert-Barness E, Olson RE, Ackerman J. Histological and ultrastructural features of atherosclerosis in progeria. Cardiovasc Pathol 1999;8:29-39.  Back to cited text no. 5
    
6.
Ding SL, Shen CY. Model of human aging: Recent findings on Werner's and Hutchinson-Gilford progeria syndromes. Clin Interv Aging 2008;3:431-44.  Back to cited text no. 6
    
7.
DeBusk FL. The Hutchinson-Gilford progeria syndrome. Report of 4 cases and review of the literature. J Pediatr 1972;80:697-724.  Back to cited text no. 7
[PUBMED]    
8.
Merideth MA, Gordon LB, Clauss S, Sachdev V, Smith AC, Perry MB, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med 2008;358:592-604.  Back to cited text no. 8
    
9.
Hamer L, Kaplan F, Fallon M. The musculoskeletal manifestations of progeria. A literature review. Orthopedics 1988;11:763-9.  Back to cited text no. 9
    
10.
Badame AJ. Progeria. Arch Dermatol 1989;125:540-4.  Back to cited text no. 10
[PUBMED]    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

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