Journal of The Association of Physicians of India ■ Vol. 64 ■ April 2016 93

Adult Progeria: Werner SyndromeNagappa Handargal1, Jananee Muralidharan2, P Praveen Sharma3, M Narayanswamy4, S Prabhu5, R Priyashree2, SG Jagadeesha2

AbstractWerner’s syndrome is an adult premature aging syndrome of autosomal recessive inheritance affecting connective tissues throughout the body.1 The exact etiology remains obscure even though biochemical and connective tissue abnormalities have been postulated.2 The disease involves multiple systems of the body and may be associated with internal malignancy.3 We report a case of a 35 year old man who presented with uncontrolled diabetes and non-healing ulcers.

1Professor, 2Postgraduate Student, 3Postgraduate Student, 4Associate Professor, 5Assistant Professor, Department of Medicine, Bowring and Lady Curzon Hospital, Bangalore Medical College and Research Institute, Bangalore, KarnatakaReceived: 03.01.2015; Accepted: 16.02.2015

Introduction

Werner’s syndrome is an adult premature aging syndrome. We

report a case of a 35 year old man who presented with uncontrolled diabetes and non-healing ulcers.

in adolescence was present. History of poor vision since past 6 months was present. He was married for 3 years but had no children. Patient had no history of similar complaints in the family. He had no siblings.

O n e x a m i n a t i o n p a t i e n t w a s conscious, cooperative; vital parameters were stable. The patient’s height was 149 cm and weight was 40 kg. Facial features were sharp with premature greying of hair and restricted mouth opening, limited to 3 fingers. Patient had a beaked nose, flattened pinna, and stretched skin over the face suggestive of scleroderma (Figures 1a and 1b).

Patient had thin arms and legs, with poorly developed musculature and predominantly central distribution of fat around the abdomen (Figure 2). Calcified yellowish nodules were present over left elbow. There was t ightness of skin over the f ingers without ulceration of fingertips (Figure 3). Dystrophic nails were observed in the toes and pale nails with loss of cuticle in the fingers Tightness of skin over lower 1/3 of legs was present bilaterally. A chronic, non-healing ulcer was present over both the medial malleoli, with base covered with slough and pale granulation tissue (Figure 4). Grafting was done for the ulcer over left medial malleolus with good graft uptake. The patient had hypogonadism

Case Report

A 35 years old male born of a non-consanguineous marriage, educated up to third standard, and working as a vegetable vendor was admitted with history of hoarseness of voice since 5 years and history of bilateral lower limb ulcers since six months. Patient was diagnosed to have diabetes 6 months ago and started on metformin 500 mg. History of poor weight gain

Fig. 1a: Sharp facial features and microstomia

Fig. 1b: Beaked nose, flattened pinna

Fig. 2: Slender arms and legs Fig. 3: Sclerodactyly

Journal of The Association of Physicians of India ■ Vol. 64 ■ April 201694

with scanty axillary and pubic hair. Dermatologist opined that skin

changes were suggestive of scleroderma.Ocular examination revealed B/L

posterior subcapsular cataracts causing diminished visual acuity (L – 6/24, R – 6/60).

ENT examination showed vocal cord paresis with thickening and atrophy of cords with phonatory gap suggestive of presbylarynx.

Investigation revealed mild anemia with a haemoglobin value of 9.8 g/dL. Patient had uncontrolled sugars with a HbA1C – 8.5 gm%. LFT revealed albumin-5.3 mg/dL and globulin-5.7 mg/dL. Rest were within normal l imits . RFT was deranged with a BUN-167 mg/dL, Sr Creat – 4.5 mg/dL. Thyroid prof i le revealed T 3 – 0.53 mIU/L, T4 – 2.14 mIU/L, TSH > 100 mIU/L and patient was started on treatment for hypothyroidism. USG Abdomen showed le f t mi ld hydroureteronephrosis with lower ureteric calculus measuring 5.3mm.

X-ray right foot showed calcification of Achilles tendon. HIV testing was negative.

B a s e d o n t h i s c o m b i n a t i o n o f symptoms and s igns, a review of literature was done and a diagnosis of Werner’s syndrome was made. Patient was given symptomatic treatment, i n s u l i n a n d r e g u l a r d i a l y s i s f o r deranged renal function. Patient is on regular follow-up.

Discussion

Werner’s syndrome (WS) is a rare autosomal recessive, adult progeroid syndrome with high prevalence in

Japan and Sardinia. 1000 of the around 1300 cases reported worldwide are from in Japan. Criteria for diagnosis as described by Irwin and Ward are shown in Table 1.4

T h i s p a t i e n t h a d t h e a b o v e features along with Type 2 Diabetes Mellitus, which is commonly seen in Werner’s syndrome. Hypothyroidism is less commonly associated with Werner’s syndrome though i t has been documented.5 There is increased incidence of malignancy in WS, the usual malignancy being fibrosarcoma, though other sarcomas and organ sp e c i f i c m a l i g n a n c i e s h a ve b e e n reported.3 However in our case there was no evidence of malignancy but careful and periodic follow up of the patient may be required as malignancies can occur later on. Premature aging contributes to the high incidence of malignancy in these patients. It is important to recognise the clinical features of WS early to rule out internal malignancies and for the purpose of genetic counselling.

References1. Epstein CJ, Martin GM, Schultz AL, et al. Werner’s Syndrome;

A Review, Medicine 1996; 45:177-221.

2. Gawkradger DK, Priestly GC, Vijayalaxmi K et al. Warner’s syndrome: Biochemical and cytogenetic studies. Arch Dermatol 1985: 121:636-641.

3. Fujiwara Y, Higashikawa T, Tatsumi M. A retarded rate of DNA replication and normal level of DNA repair in Werner’s syndrome fibroblasts in culture. J Cell Physiol 1997; 92:365-74.

4. Irwin GW, Ward PB. Werner’s Syndrome. With a report of two cases. Am J Med 1953; 15:266–71.

5. Zantour B, Messaoud R, Zouali M, Ladjimi A, Braham H, Hamza H, et al. Werner’s syndrome and endocrine disorders. Ann Endocrinol (Paris) 2003; 64:205-9. French.

Fig. 4: Chronic non-healing right lower limb ulcer

Table 1: Diagnostic criteria and features in our patient

Irwin and ward criteria

Features in our patient

Characteristic habitus and statureShort stature (from adolescence) PresentSlender extremities with stocky trunk PresentBeak-shaped nose PresentPremature senilityPremature grey hair PresentPremature baldness PresentAtrophic skin PresentWeak and high-pitched voice PresentArteriosclerosis PresentJuvenile cataracts PresentScleroderma-like changesAtrophic skin and subcutaneous tissues

Present

Circumscribed hyperkeratosis Not seenUlcers over the malleoli of the ankles, Achilles tendon, heels and toes

Present

Other manifestationsTendency to diabetes mellitus PresentHypogonadism PresentOsteoporosis PresentLocalised calcification PresentTendency to occur in siblings No siblings