Progeria in siblings: a rare case report.

Progeria, also known as Hutchinson-Gilford syndrome, is an extremely rare, severe genetic condition wherein symptoms resembling aspects of aging are manifested at an early age. It is an autosomal dominant disorder. It is not seen in siblings of affected children although there are very few case reports of progeria affecting more than one child in a family. Here we are presenting two siblings, a 14-year-old male and a 13-year-old female with features of progeria, suggesting a possible autosomal recessive inheritance.

Introduction

Progeria is a rare premature aging syndrome characterized by retarded physical development, abnormal facies, skeletal abnormalities and early onset of scleroderma. It was first described in 1886 by Jonathan Hutchinson[1] and was also described independently in 1897 by Hastings Gilford.[2] The condition was later named Hutchinson-Gilford progeria syndrome (HGPS). Approximately, 100 cases have been formally identified in medical history.[3] Affected children are normal at birth and growth retardation is noticed from first year of life. By the second year, skin becomes thin and shiny in some areas but lax and wrinkled in other areas. Later, progressive mottled hyperpigmentation develops. Nails become dystrophic. Scalp and body hair becomes sparse. Dentition is abnormal and delayed. Death usually occurs in the second decade as a result of severe generalized atheroma. It usually occurs due to sporadic autosomal dominant mutation in the LMNA gene.[4]

Case Report

Two siblings, a 14-year-old male child and a 13-year-old female child, born to third-degree consanguineous parents, presented with abnormal facies and prematurely aged appearance. History from the mother revealed that the antenatal period was uneventful during both the pregnancies. Both the children were delivered at term by cesarean section and their birth weight was more than 2.75 kg. Mile stones were attained normally till 9 months of age after which growth retardation was noticed in both the children.

Height of the male and female child was 91 and 90 cm, respectively, while their weight was 11 and 10 kg, respectively. They had bird like facies with patent anterior fontanalle, frontal bossing, prominent eyes, protruding ears, beaked nose and micrognathia [Figure 1]. Teeth were crowded and irregularly erupted [Figure 2]. Eyebrows were absent in the male and sparse in the female. They had high pitched voice and their intelligence was normal.

Figure 1

Beaked nose, protruding ears and micrognathism in both children

Figure 2

Crowded and irregularly erupted teeth

Dermatological examination revealed shiny hyperpigmented skin over forhead and thin, and wrinkled skin over hands and feet. There were hypopigmented macules interspersed between hyperpigmented macules in the chest and abdomen [Figure 3]. Finger and toe nails were dystrophic. Scalp hair was sparse in the male and normal in the female. They had no photosensitivity.

Figure 3

Thin and wrinkled skin over the hands with dystrophic nails

Their blood count, hemoglobin percentage, blood sugar, renal and liver parameters and lipid profile were within normal limits. Total thyroxine (TT4), thyroid stimulating hormone (TSH), growth hormone (GH) levels were normal and there was no evidence of primary endocrinological dysfunction. Urine mucopolysaccharides were negative. USG abdomen revealed a mild hepatomegaly in the male child and no significant findings in the female child. Cardiac evaluation showed that ECG was within normal limits. Echo showed mild anterior mitral leaflet thickening and trivial aortic regurgitation in the male child and mitral valve prolapse with trivial mitral regurgitation in the female child but their left ventricular function was normal. Male child complained of visual disturbances and on ophthalmologic examination, he was found to have hypermetropia and pseudopapillitis. The female child had a swelling in the gums and was diagnosed as peripheral ossifying fibroma in the dental OPD. CT and X-ray skull showed normal facial and skull bones with open anterior fontanalle. Skin biopsy showed thinned out epidermis and increased collagen in the mid-dermis.

A diagnosis of progeria was made based on the clinical findings of short stature with bird like facies, hair and nail changes and normal intelligence.

Discussion

Short stature, bird like facies and normal intelligence are distinctive features of progeria. In our case, the skin changes and normal intelligence excluded the other disorders with short stature and abnormal facies like bird headed dwarfism. The early age at onset excluded pangeria. Typical facial changes ruled out acrogeria. The lack of photosensitivity ruled out Rothmund thomson syndrome. Absence of disproportionately large extremities, ocular changes and photosensitivity helped to exclude Cockayne syndrome.

Classical Hutchinson–Gilford progeria syndrome is almost never passed on from parent to child. It is usually caused by a new (sporadic) mutation during the early division of the cells in the child.[5] It is usually genetically dominant; therefore, parents who are healthy will normally not pass it on to their children. Affected children rarely live long enough to have children themselves. They typically live about 13 years, although many have been known to live into their late teens and early twenties and rarely some individuals may reach their forties.

Clinically, healthy parents with affected siblings in the family favor autosomal recessive pattern of inheritance, as in our case. There are very few case reports[6-8] of progeria in siblings with an autosomal recessive pattern of inheritance, which have been documented in India. We add on to this rare case list by reporting progeria in two children of the same family, suggesting an autosomal recessive pattern of inheritance.