American Journal of Medical Genetics 36431-433 (1990)

Brief Clinical Report

Hutchinson-Gilford Progeria: Familial Occurrence ~

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H. Parkash, S.S. Sidhu, R. Raghavan, and R.N. Deshmukh Department of Dental Surgery, All-India Institute of Medical Sciences, New Delhi, India ~

We report on 2 brothers with Hutchinson-Gilford progeria. These patients have 2 unusual findings, i.e., marked resorption of the mandible along with loss of teeth in the elder sib and prolonged survival. Both sibs are still alive and active at the age of 32 and 24 years.

Physical Manifestations

The 2 brothers weighed 25 and 30 kg, respectively, and were 144 and 145 cm tall. Both had marked g o d h failure, normal psychomotor development, a “horseriding” stance with wide-based shuffling gait, and difficulty in standing without support. Besides this, they could not walk barefoot but needed the support of platKEY WORDS: autosomal recessive inheriform-soled slippers; flexion at the knees or squatting on tance, progeria the floor was impossible. The elder sib had thin bony legs with prominent ankles and toes. The 5th toe of both feet had an “eroded” INTRODUCTION appearance. His arms were thin with small wrists and Hutchinson-Gilford progeria (HGP) is a rare genetic large elbow joints. He gave a history of fracture of the disorder with prematurely accelerated aging and a bi- left arm. He was operated on for abduction tenotomy in zarre aged phenotype from age 2 years. The reported his left lower limb 3 years ago. Both brothers had short incidence of HGP is about 1 per 250,000 live births in the terminal phalanges of both hands and feet. The nails USA [Bergsma, 1979; Wiedmann, 19871. HGP has been were small, thin, and dystrophic with a bluish discolorareported in over 100 patients [Wiedmann, 19871. tion. Most HGP patients are sporadic cases. Egyptian sisThe skin over the body of the elder sib was pigmented ters with consanguineous parents were reported by with a dry, wrinkled appearance and a marked lack of Gabr et al. [1960]. A set of sibs was reported by Rava subcutaneous fat. Both had hypoplastic clavicles (Fig. [19671 and Frankyln [19761 and Erecinski [19611. A pair 2). They had a normal testicular size with a small of male monozygotic twins with progeria was studied by phallus. The pubic hair was scanty, axillary hair was Viegas et al. [19741. De Busk [1972] had extensively absent, and facial hair was absent although the younger reviewed progeria and found evidence of parental con- sib had minimal moustache hair. sanguinity in 3 of 19 families. These findings are consisThe cranium was abnormally shaped; anterior and tent with autosomal recessive inheritance. Cases have posterior fontanelles were open. There was alopecia with been reported from all continents except Australia. In a prominent scalp veins. The head circumference of both Japanese patient normal chromosomes were reported the brothers was 50.5 and 51 cm. but there is no written or photographic proof of the The other facial changes were exophthalmos, a “birddiagnosis [De Busk, 19721. Two cases from India have beak” appearance due to micrognathia, and a thin nose been reported [De Busk, 19721.This is the third report of (Fig. 2). Both had prominent ears with absent lobules; HGP in brothers. the elder sib had fan-shaped anteverted ears. The younger brother had facial cyanosis and both had a thin, CLINICAL REPORT high-pitched voice. A familial progeria syndrome was diagnosed in 2 The elder sib had only 2 teeth in the lower jaw. There brothers aged 32 and 24 years from a sibship of 7 (4M, was protrusion of the upper anterior teeth over the lower 3F, Fig. 1). They were from the Indo-Nepal border and lip with a habitual open bite and open lips. The arches from a low socio-economicstatus. There was no parental were asymmetrical, the upper arch being V-shaped with consanguinity. No other relatives were affected in at a long palate and an inferiorly placed uvule. The mandileast 2 generations. Their parents were 40 and 23 years ble in the symphysis region was hypoplastic, and only a old at the time of birth of the elder sib. part of body and ramus was palpable. The younger sib had a full complement of teeth with class I1malocclusion and a cross-bite of the upper lateral Received for publication June 7,1989; revision received Novemincisors. There was an edge-to-edgebite, competent lips, ber 15, 1989. Address reprint requests to Dr. Hari Parkash, Department of and a V-shaped high palate which was also long with an Dental Surgery, All-India Institute of Medical Sciences, New inferiorly placed uvula. A notch in the mandibular symphysis region was also noted. Delhi-110029, India. 0 1990 Wiley-Liss, Inc.

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IV

19-24

25-26

27Q8

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6% Fig. 1. Pedigree.

Laboratory Investigations The growth hormone responses to insulin and arginine infusions were normal in both brothers. They had normal blood count, blood urea, nitrogen, chloride, so-

dium, potassium, calcium, phosphorus, alkaline phosDhatase. and electroDhoresis of serum Drotein. The urihary 17-hydroxy-&rticosteroid excietion, 17-ketosteroid, and thyroxin function tests were also normal in both brothers.

Fig. 2. Approximation of shoulders, exophthalmos,and “bird-beak’’appearance in the (A)elder and (€3) younger sibs, respectively.

Hutchinson Progeria

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Fig. 3. Panorex view of the mandible showing resorption of the body and the ramus and presence of only 2 teeth (elder sib).

Radiological Manifestations Skull and facial bones. The cranial cavity was of normal size; however, hypoplasia of facial bones had resulted in craniofacial disproportion. The cranial bones were thin and the anterior fontanelles and suture were still open. In the case of the younger sib wormian bones were present. The base of the skull was normally developed and the sella turcica was elongated in both cases. The length of the ramus and the body of the mandible were very short in the younger sib while in the elder sib, the body of the mandible was almost completely resorbed and only a part of body and ramus could be seen (Fig. 3). All four 3rd molars were impacted and there was less crowding of teeth in the younger sib. Thoracic cage. It was narrow and small in size. Distal clavicles were thin and ribs were narrow. Long bones. Due to thin cortices, the long bones appeared gracile. Broadened, poorly tubulated metaphyses were apparent in both the patients. Phalanges. The most characteristic change in both the brothers was the progressive loss of bone from the distal phalanges of the fingers and toes bilaterally (Fig. 4) Both the sibs had a severe degree of coxa valga and moderate genu valgum. DISCUSSION Progeria is a rare disorder. These children develop normally during the first few months of life but by age 6 months to one year, the striking manifestations of aging become noticeable [Villeeet al., 19691. Most of the manifestations in these 2 brothers are in agreement with the findings reported in the literature, except for marked resorption of the mandible found in the elder sib. The most striking radiographical finding has been gradual resorption of the mandible, which has not been reported so far; only hypoplasia of the mandible has been found by several workers [De Busk, 19721. Patients with progeria have a limited life span. The oldest survivor reported lived 29% years but the present elder sib is already age 32 years and is doing quite well. HGP differs from the normal aging process and these differences are most striking and thus cannot be considered as a phenocopy of normal aging. REFERENCES Bergsma D (1979): “Birth Defects Compendium,” 2nd ed. The National Foundation-March of Dimes. New York: Macmillan Press Ltd., 886 pp.

Fig. 4. Radiograph of (A)hands and (B)feet demonstrating progressive loss of distal phalanges of fingers and toes (younger sib).

De Busk FL (1972):The Hutchinson-Gilfordprogeria syndrome: h p o r t of 4 cases and review of the literature. J Pediatr 80:697-724. Erecinski K (1961): Bittel-Dobrzynsk N and Mostowiec S: Zespol progeriiu dwoch braci. Pol 5 g Lek 16:806-809. F’ranklyn P P (1976): Progeria in siblings. Clin Radio1 27:327-333. Gabr M, Hashem N, Hashem M, Fahmi A, Safouh M (1960):Progeria, a pathologic study. J Pediatr 57:70-77. Rava G (1967): Suun nucleo familiaredi progeria. Minerva Med 58:1505-1509. Viegas J , Souza PLR, Salzano FM (1974): Progeria in twins. J Med Genet 11:384-386. Villee DB, Nichols G, Jr, Talbot NB (1969): Metabolic studies in two boys with classical progeria. Pediatrics 43:207-216. Wiedmann HR (1987): Progeria. In Gomez MR (ed): “Neurocutaneous Diseases-A Practical Approach.” Boston: Butterworth Publishers, pp. 247-253.

Hutchinson-Gilford progeria: familial occurrence.

We report on 2 brothers with Hutchinson-Gilford progeria. These patients have 2 unusual findings, i.e., marked resorption of the mandible along with l...
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