Description

A male toddler born of non-consanguineous marriage, with normal perinatal period, presented with painless distention of abdomen as well as diffuse thickening of skin over the abdomen since 2 months of age, which progressed over the next few months to involve the trunk as well as bilateral extremities, with gradual spontaneous resolution over a year to leave mottled pigmentation and minimal remnant induration. This was accompanied by near-complete loss of hair from all over the body. A wide-based gait was present with bowing of legs. He had protuberant eyes, decreased facial fat and wrinkled, shiny skin over the dorsae of hands and feet (figure 1). Prominent veins were evident on the scalp. Teeth, nails, palms and soles were normal. There was mild global developmental delay and failure to thrive (weight for age, height for age and weight for height <−3SD). There was no history of photosensitivity, recurrent infections, ocular or any other systemic complaints. The family history was unremarkable. Radiographs of hands revealed bilateral acro-osteolysis and scannogram showed bilateral coxa valga, but no evidence of rickets or osteopenia (figure 2). Routine investigations were normal except for mild anaemia (Hb=111 g/L). Trichoscopy and trichogram showed unmedullated normal hair shaft with pigment dilution. With these clinical features, a diagnosis of Hutchinson-Gilford progeria syndrome (HGPS) was considered. Sanger sequencing revealed a heterozygous mutation in exon 11 of Laminin A gene, c.1824C>T (p.G608G), which is known to occur in >90% of patients with HGPS.1 Further workup for serum insulin levels, fasting lipid profile and echocardiography was within normal limit.

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Figure 1

(A) Trunk showing mottled brown hyperpigmentation with mild diffuse induration. (B) Near-total alopecia of scalp with prominent veins; (c) atrophic, wrinkled skin on dorsum of hands.

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Figure 2

(A) X-ray of bilateral hands, anterioposterior view, showing acroosteolysis (blue arrows). (B) Scannogram showing bilateral coxa valga (red arrow).

Progeroid syndromes are rare, with reported incidence about 1 in 4–18 million.1 They broadly include nuclear laminopathies and DNA repair defects and the latter is often associated with photosensitivity.2 They are characterised by premature onset of age-related pathologies in various systems, including the skin, immune system (infections, autoimmunity and malignancies), skeletal (osteoporosis), vascular (atherosclerosis), neurological as well as metabolic alterations (insulin resistance and diabetes mellitus) and growth failure. HGPS/progeria is the most common and well-studied progeroid laminopathy, occurring sporadically as an autosomal dominant disorder. Skin abnormalities including alopecia (100%), transient sclerodermoid changes (78%), prominent skin vasculature (22%) and dyspigmentation (16%) are often the initial clinical signs in HGPS along with failure to thrive and the characteristic facies.3 Unlike some other progeroid syndromes, the immune system remains unaffected in HGPS, with normal IgM, IgG, IgA levels as well as largely normal lymphocyte phenotyping.4 The average lifespan is 14.6 (range 1.6–27.5) years,5 with the most common cause of mortality being cardiovascular. The differential diagnosis include atypical progeria syndromes, mandibuloacral dysplasia, acrogeria, metageria, neonatal progeroid syndromes, Penttinen syndrome; Cockayne syndrome and Rothmund-Thompson syndrome. Knowledge of specific clinical features narrows the differential to test for specific mutations, thus bringing down the cost of genetic testing. A correct diagnosis holds prognostic value as well as the possibility of trial of farnesyl transferase inhibitors such as lonafarnib, which has shown improved mortality outcomes in these patients with an HR of 0.12.6 However, this could not be tried in our case due to lack of availability. The child remains under regular follow-up.