Statistics from Altmetric.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
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.
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.
Early clinical constellation of findings that point towards the genetic diagnosis of Hutchinson-Gilford progeria includes sclerodermoid skin change, alopecia, cutaneous dyspigmentation, prominent veins and failure to thrive.
Patients of Hutchinson-Gilford progeria should be screened for cardiac and metabolic comorbidities and kept under regular follow-up, as the most common cause of death is cardiovascular.
Farnesyl transferase inhibitors may have a mortality benefit, and there is currently an ongoing trial in combination with everolimus (NCT02579044).
Patient consent for publication
Contributors The following authors were responsible for drafting of the text, sourcing and editing of clinical images, investigation results, drawing original diagrams and algorithms, and critical revision for important intellectual content: AS, BS and GS.The following authors gave final approval of the manuscript: AS, BS, GS.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.