Bloom's syndrome–‐a first report from India
Authors: Reddy B. S. N. , Kochhar Atul M. , Anitha M. , Bamezai Ramesh 
Published: March 2003

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 Azad Medical College and Lok Nayak Hospital, New Delhi, India.

The child was apparently normal until the age of 6 months when his mother noticed an erythematous eruption with small blisters and mild discomfort over the face on exposure to sunlight. Gradually, the eruption became more progressive, extending to the forehead, nose, and ears with the development of oozing, crusting, atrophy, and telangiectasias over the face, despite treatment. 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 complaints, Raynaud's phenomenon, alopecia, discoloration of urine on standing, and chronic systemic or cutaneous infections could be obtained. The patient is a product of a full‐term pregnancy with normal vaginal delivery of nonconsanguineous parents. His developmental milestones were delayed, with sitting 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 land mass, bounded by the Himalayan mountains to the north‐west, lush green forests to the east, and the scenic Kashmir valley to the north; the land tapers 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 and union‐territories with Christians, Hindus, Muslims, Sikhs, and people from other religions. Among the Hindus, several castes exist, such as ‘‘Brahmins,’' ‘‘Kshatriyas’' (Rajputs–‐the warrior clan), ‘‘Vaishyas,’' and ‘‘Shudras,’' classified according to their profession from ancient times. The parents of our 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 Uttar Pradesh ( Fig. 1). There was no history of consanguinity in the family members presented in the pedigree chart (
Fig. 2).

Political map of India showing the neighboring countries, location of the patient's home in the state of Uttar Pradesh (U.P), and Multan from where the parents of the patient had migrated

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Pedigree chart of the BS child

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The patient's father (39 years) and mother (35 years) were apparently normal 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 11‐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 examined 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 growth, 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 pointed nose, high arched palate, and dolichocephalic skull

( Fig. 3).

Full‐length profile of the 6‐year‐old BS child showing proportionate dwarfism

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Dermatologic examination revealed characteristic facies with diffuse erythema extending onto the forehead, nose, and ears, with thin atrophic scarring, telangiectasias, and mild hypertrichosis. A circular, superficial, bleeding ulcer of 2 cm × 1.5 cm was located on the right cheek, extending onto the margins of the lower eyelid ( Fig. 4). The borders of the ulcer were not raised but covered with yellowish crusts, and mild ectropion of the eyelid was also seen. In addition, he also had hyperpigmented macules (café‐au‐lait spots) of varying sizes, measuring from 1 to 3 cm in diameter, over the trunk, back, and sacral region which also had a small circular dimple. Two circular hypopigmented macules of 1 cm in diameter were present over the chest. He also had clinodactyly of the fingers; his nails were normal but for minimal 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 retardation with an IQ of 60–65 on psychometric examination by the Adaptive Behavior Score.

Close‐up of the face showing multiple telangiectasias, scarring, and ulceration below the right eye

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Routine hematologic and radiologic studies revealed no abnormalities. Immunologic studies including lupus erythematosus (LE) cell and ANA were negative. The biochemical profile of blood and urine was negative for porphyrins. Histopathologic examination of the skin over the face on hematoxylin and eosin staining revealed changes suggestive of chronic actinic damage with epidermal atrophy, hydropic degeneration of the basal cell layer, and dermal edema, 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 cultures 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 °C 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 standard fluorescent plus Giemsa (FPG) technique (Goto K, Akenmatsu T, Shimazu H, Sugiyama T. Simple differential Giemsa staining of sister chromatids after treatment with photosensitive dyes and exposure to light and the mechanism of staining. Chromosome 1975; 53: 223–230) carried out routinely in the laboratory (Bamezai R, Shiraishi Y. Cell cycle progression and SCE rate of Bloom syndrome cells with/without co‐cultivation in the presence/absence of normal cells. Exp Cell Res 1986; 164: 163–173; Bamezai R, Kumar N. Sleep deprivation in human males and its effect on SCE rates in chromosomes–‐a preliminary study. Mutat Res 1992; 283: 229–232). Better chromosome plates (31 plates) were identified and the terminal exchanges between two chromatids of the same chromosome were scored as 1 sister chromatid exchange (SCE) and the symmetrical exchanges as 2 SCEs.

Results showed a high frequency of SCEs ( Fig. 4) in the patient, with the mean SCE per cell being 72. The standard error calculated from the Sigma Stat program was 3.25 and the standard deviation was 26.9. Further chromosomal abnormalities, such as breaks, deletions, triradials, quadriradials, and dicentric chromosomes, were observed. Cytologic studies of the father's blood did not reveal any abnormality.

The facial erythema improved with the application of topical sunscreen ointments, but the ulceration over the face showed no signs of healing despite treatment with oral and topical antimicrobials, zinc, vitamins, and hematinics. The scarring and telangiectasias over the face persisted. The child was sent home with adequate counseling to avoid exposure to sunlight and to report to the clinic quarterly for regular check‐ups.