Bloom's syndrome - a first report from India

A 6-year-old boy presented with complaints of redness and scarring over the face to the outpatient clinic of the Dermatology Department of Maulana Aza d Medical College and Lok Nayak Hospital, New Delhi, India. The child was apparently normal until the age of 6 months when his mother n oticed an erythematous eruption with small blisters and mild discomfort ove r the face on exposure to sunlight. Gradually, the eruption became more pro gressive, extending to the forehead, nose, and ears with the development of oozing, crusting, atrophy, and telangiectasias over the face, despite trea tment. Over the last 3 months, he had developed ulceration of the skin over the right cheek just below the lower eyelid without any signs of healing. No history suggestive of constitutional symptoms, bowel and bladder complai nts, Raynaud's phenomenon, alopecia, discoloration of urine on standing, an d chronic systemic or cutaneous infections could be obtained. The patient i s a product of a full-term pregnancy with normal vaginal delivery of noncon sanguineous parents. His developmental milestones were delayed, with sittin g at 2.5 years and standing and speech at 3 years. Our patient is a Hindu by religion and Rajput by caste. India is a vast lan d mass, bounded by the Himalayan mountains to the north-west, lush green fo rests to the east, and the scenic Kashmir valley to the north; the land tap ers into the Indian Ocean at the southern peninsula where the Bay of Bengal and Arabian Sea meet. India is a republic consisting of different states a nd union-territories with Christians, Hindus, Muslims, Sikhs, and people fr om other religions. Among the Hindus, several castes exist, such as "Brahmi ns," "Kshatriyas" (Rajputs-the warrior dan), "Vaishyas," and "Shudras," cla ssified according to their profession from ancient times. The parents of ou r patient had migrated from the Multan region of Pakistan back to India at the time of partition, and are presently residing in the hilly region of Ut tar Pradesh (Fig. 1). There was no history of consanguinity in the family m embers presented in the pedigree chart (Fig. 2). The patient's father (39 years) and mother (35 years) were apparently norma l and had four children. The eldest child is a normal 14-year-old girl. The second was a girl who died at the age of 2 years, presumably of a similar ailment. The third is a normal 1 I-year-old boy, and the last is the 6-year -old boy brought to our clinic. A similar problem has been said to exist in a 15-year-old male paternal cousin of the patient, but he has not been exa mined by us as he does not reside in the area. Physical examination of the patient revealed an alert and active boy with a pleasing personality, but an irritable mood. He had definite stunted growt h, and his body weight (10 kg), height (91 cm), and head circumference (46 cm) were all below the fifth percentile. His voice was high pitched and his hair and eyes were brown, but normal. He had a small, thin body frame and a delicate, tender, narrow, bird-like facies with small mandible and pointe d nose, high arched palate, and dolichocephalic skull (Fig. 3). Dermatologic examination revealed characteristic facies with diffuse erythe ma extending onto the forehead, nose, and ears, with thin atrophic scarring , telangiectasias, and mild hypertrichosis. A circular, superficial, bleedi ng ulcer of 2 cm x 1.5 cm was located on the right cheek, extending onto th e margins of the lower eyelid (Fig. 4). The borders of the ulcer were not r aised but covered with yellowish crusts, and mild ectropion of the eyelid w as also seen. In addition, he also had hyperpigmented macules (cafe-au-lait spots) of varying sizes, measuring from 1 to 3 cm in diameter, over the tr unk, back, and sacral region which also had a small circular dimple. Two ci rcular hypopigmented macules of 1 cm in diameter were present over the ches t. He also had clinodactyly of the fingers; his nails were normal but for m inimal clubbing. The right testis was small in size and the left testis had not fully descended to the scrotum. The rest of the cutaneous and systemic examination revealed no other abnormality, except for mild mental retardat ion with an IQ of 60-65 on psychometric examination by the Adaptive Behavio r Score. Routine hematologic and radiologic studies revealed no abnormalities. Immun ologic studies including lupus erythematosus (LE) cell and ANA were negativ e. The biochemical profile of blood and urine was negative for porphyrins. Histopathologic examination of the skin over the face on hematoxylin and eo sin staining revealed changes suggestive of chronic actinic damage with epi dermal atrophy, hydropic degeneration of the basal cell layer, and dermal e dema, with dilatation of the vessels and a chronic inflammatory infiltrate in the dermis. Due to nonavailability, immunofluorescence studies were not carried out. Peripheral blood was collected from the patient and whole-blood cu Itu res were performed with and without 10% serum supplementation. To all cultures, 10 mg/mL of phytohemagglutinin (PHA) was added at the time of culture. In addition, bromodeoxyuridine (10 mg/mL) was added to some cultures either at 0 h or at 24 h after culture. These cultures were incubated at 37 degreesC for 72 h and harvested after adding colchicine (0.05 mg/mL) at 69 h after culture. Slides were prepared by the air dry method and were stained using the stand ard fluorescent plus Giemsa (FPG) technique (Goto K, Akenmatsu T, Shimazu H , Sugiyama T. Simple differential Giemsa staining of sister chromatids afte r treatment with photosensitive dyes and exposure to light and the mechanis m of staining. Chromosome 1975, 53:223-230) carried out routinely in the la boratory (Bamezai R, Shiraishi Y. Cell cycle progression and SCE rate of Bl oom syndrome cells with/without co-cultivation in the presence/absence of n ormal cells. Exp Cell Res 1986; 164: 163-173; Bamezai R, Kumar N. Sleep dep rivation in human males and its effect on SCE rates in chromosomes-a prelim inary study. Mutat Res 1992; 283: 229-232). Better chromosome plates (31 pl ates) were identified and the terminal exchanges between two chromatids of the same chromosome were scored as 1 sister chromatid exchange (SCE) and th e symmetrical exchanges as 2 SCEs. Results showed a high frequency of SCEs (Fig. 4) in the patient, with the m ean SCE per cell being 72. The standard error calculated from the Sigma Sta t program was 3.25 and the standard deviation was 26.9. Further chromosomal abnormalities, such as breaks, deletions, triradials, quadriradials, and d icentric chromosomes, were observed. Cytologic studies of the father's bloo d did not reveal any abnormality. The facial erythema improved with the application of topical sunscreen oint ments, but the ulceration over the face showed no signs of healing despite treatment with oral and topical antimicrobials, zinc, vitamins, and hematin ics. The scarring and telangiectasias over the face persisted. The child wa s sent home with adequate counseling to avoid exposure to sunlight and to r eport to the clinic quarterly for regular check-ups.