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Bloom's Syndrome. I. Genetical and Clinical Observations in the First Twenty-Seven Patients JAMES GERMAN'

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Bloom's Syndrome. I. Genetical and Clinical Observations in the First Twenty-Seven Patients JAMES GERMAN' Bloom's Syndrome. I. Genetical and Clinical Observations in the First Twenty-seven Patients JAMES GERMAN' INTRODUCTION Bloom's syndrome, also termed congenital telangiectatic erythema and stunted growth, was first recognized and described as a clinical syndrome by Dr. David Bloom (1954a). In 1966, he reviewed his observations and experiences with the condition and named its "three cardinal features" (Bloom, 1966): (a) telangiectatic erythema ap- pearing in infancy, affecting almost exclusively the butterfly regions of the face, cheeks, nose, margins of the eyelids, lips, forehead, and ears, but occasionally also affecting the dorsa of the hands and the forearms; (b) sun sensitivity, so that the telangiectatic skin lesions often first appear or become accentuated in summertime and usually ameliorate when protected from sunlight; and (c) stunted growth, the most conspicuous feature of the syndrome. This last feature is distinguished by smaller than average size both at birth and also during various periods of childhood and adulthood. The maximum height achieved has been 161.3 cm, in a boy who is now 17 years old; no other individual has exceeded 148 cm (Table 1, Col. X). The body proportions appear approximately normal, but the patients usually are delicate and slender. There is disproportionate microcephaly, which is accentuated by the delicacy and narrowness of the face. The affected individuals bear a striking general resemblance to one another because of the small, narrow face, the dolichocephalic head, the localized red lupus erythematosus-like facial skin lesion, and the conspicu- ous dwarfism. The skin lesion tends to become less severe as the individual grows older, but sometimes scarring, atrophy, depigmentation, and loss of eyelashes become prominent and disfiguring. The affected persons usually are of average intelligence, and they tend to be affable but may develop unusual personality features as psycho- logical consequences of their unusual appearance and size. Their health is generally good, although sometimes feeding difficulties occur in infancy, and many have had increased numbers of infections of the respiratory tract or ears requiring antibiotic therapy in infancy and early childhood. Satisfactory treatment for neither the telan- giectasia nor the growth retardation has been found. Three additional recent observations have increased the scientific importance of this rare condition and have stimulated a series of reports from this laboratory (Ger- Received September 3, 1968. This investigation was supported by Public Health Service research grant HD 04134 from the National Institute of Child Health and Human Development and by grant E-461 from the American Cancer Society. l The New York Blood Center, New York, New York 10021. 196 BLOOM'S SYNDROME 197 man, 1964; German et al., 1965; German and Crippa, 1966a, b; German, 1969; Sawitsky et al., 1965; Sawitsky et al., 1966), and others will follow (German and Bloom, in preparation; German and Crippa, in preparation; German and La Rock, in preparation; Passarge and German, in preparation). These observations are: (a) Familial clustering (Szalay, 1963; Wolf, 1963) and an increased frequency of parental consanguinity and Jewish ancestry have suggested a recessive pattern of inheritance (German et al., 1965), but the genetic analysis of the condition has awaited recognition of a larger number of affected families. (b) Cytogenetic studies in 22 affected indi- viduals have demonstrated a consistent abnormality in cells cultured in vitro, a tendency to chromosomal breakage and rearrangement (German, 1964; German et al., 1965; German and Crippa, 1966a, b; Grouchy, 1966; Hooft et al., 1967; Keutel et al., 1967; Landau et al., 1966; Sawitsky et al., 1965; Sawitsky et al., 1966; Sizonenko et al., 1967a, b), and, as a consequence, a high incidence of aneuploidy (German and Crippa, 1966a). Breakage and rearrangements are also found in moderately increased numbers in cultured cells from some parents of individuals with this syndrome (Sawitsky et al., 1966; German, unpublished observations). (c) There is an increased expectancy for the development of malignant neoplasia for individuals affected with the syndrome (German et al., 1965; Sawitsky et al., 1965, 1966). The present report, which is the first in a series on Bloom's syndrome, consists of various observations which have been made on the first 27 individuals to have been recognized as affected with this rare disorder. The purposes of the report are to add to the understanding of the clinical features and course of the disorder and to compile the evidence required for definition of its genetics. MATERLALS For clarity and conservation of space, a tabular style for presenting most of the observations has been chosen (Tables 1-7; Figs. 1, 4, and 5). The tables and figures contain cross-references, so that from them a fairly complete description of each individual can be reconstructed. In Column I of Table 1, each of the 27 affected persons has been assigned a case identification number in the approximate order in which they were recognized or reported in medical journals. Each person is further identified by the first letters in his first name and family name. (Names are not known for patients 8, 9, and 21, so the initials of the author reporting each case were employed.) The initials of the family name of the propositus and the identification number of the propositus are used to identify each pedigree in Figure 1. These identi- fying numbers and initials will be employed consistently in subsequent reports from this laboratory. Photographs of some of the individuals in the series are shown in Figures 2 and 3. Ascertainment of Affected Families Ascertainment in these families was through an affected individual, and these individuals have come to my attention during the past eight years in one of the follow- ing ways: (a) Through Dr. David Bloom. The first patient to enter into the series (2, Su. Bu.; Fig. 2i, j) was studied in 1960 at the request of Dr. Bloom, who felt that the etiology of the syndrome might be an imbalance of the chromosomal complement. TABLE 1 SUMMARY OF DATA CONCERNING THE FIRST 27 INDIVIDUALS A blank space indicates that the = I II III IV V VI VII VIII Ix x XI XII XIII I_ -I _s n .b 0 bo 40 4) s .0 . > Cd -e O -o -o .0 0 Z Bn H0 -c cd 0 0 P-4 .i .z I._ 0 E400 00 E 11 cd .) 0)0aw Po p0 Q0 + cd x 3.. 1.... Ce. So. '33 M 29/29 1,815 25/obese 25/145 + 2.. Su. Bu. '50 F 28/25 +++ 1,362 13/31 13/ 132 3/40 ++ 3.... Ho. Co. '49 M 1,760 17/55.5 17/161.3 28/21 3.5/43.8 + 4.... Ge. Ho. '33 M 33/25 ± 1,910 33/54 33/146 5.... Ja. Oa. '34 M 36/28 + 1,986 29/36 30/142.5 32/47 ±Z( 6.... De. Sou. '47 M 27/25 2,116 18/35 18/ 143 +7~ ± 18/148 += + 7.... IRFo. Ta. '46 M 2,215 18/40 +n~ + 8.... Ka.' '57 M 2,350 2. 7/8.3 45 2.7/78 +n ++ ± 9.... Ka.' '49 M + 2,000 10/17.3 10/118 +n ++ + 10.... Gr. St. '50 M 28/28 2,016 10/14.5 10/112 10/45.7 + 11.... Ia. Th. '49 M 28/26 ++ 2,100 11/18.9 11/119 11/50.3 12.... De. Th. '53 F 32/30 2,043 8/12.4 8/102 8/49.5 13.... De. Si. '54 F ++ 1,590 5/11 ++ 14.... le. Si. '55 M 1,818 5/11 15.... Ma. Ro. '61 M 30/25 1,760 4/9.4 39.4 4/86 + 16.... Et. Fi. '61 F 42/31 1,532 2.3/5.8 2.3/74 17.... Ch. Sm. '57 M 18/20 2,485 7/16 7/102 5/45.7 18.... La. Sm. '60 M 21/23 + 2,925 5/9.6 5/81 5/43.2 + 19.... Sy. Tik. '42 F 4-2/36 32 wk. 1,600 23/35 23/134 + 20.... Bo. Le. '65 M 30/25 + 1,980 1/5.2 41.5 1/61 1.1/39 21.... La.' '(0 M 25/27 2,000 5.7,/9.9 46 5.7/92 4.5/45.2 + M + 46.2 11/127 13/46.9 ++ 22.... El. Ha. '56 43/32 ++ 2,371 11/17 + 23.... Na. Ha. '59 44/33 2,279 8/23 46.2 8/126 12/47.4 + 24.... Ro. So. '32 F 27/27 ++ 1,362 32 wk. + 25.... St. Ti. '63 F 2,130 2.5/7.5 2.5/76 1.5/42 26.... Sa. Ti. '64 F + 2,229 1.3/6.3 1.30/1 1/40.8 27.... Ly. Se '64 F 25/26 + 1,960 2/6.8 2/74 0.09/32.7 M 2,100 4/91 28.... Cas.' '61 4/11.3 2. +- 29.... Cas.2 '62 F 2,300 2.5/8 2/745/77.4 30.... Ke.' '64 M 29/27 1,350 2/6.5 40 + 31.... Ca. D. '55 F 1,980 8.2/13.1 8.2/105 8.2/46.5 32.... Mi. Ko. '62 M 30/25 1,307 5/9.1 5/87.5 + 33.... Be. Be. '54 F 42/ 2,359 198 To BE RECOGNIZED (1-27) AND SIX MORE RECENTLY RECOGNIZED (28-33) information could not be obtained. = = XIV XV XVI XVI.I XVIII XI)K. xx xxI XXII ..l 1- -! I0 :: r. _ 4'1 0 0 cd Q~~~~ , .61 Ou 0 : -4 0 0 0 '-00 .0 p4 0 P4 - *0 v) U 0 .0 c, ._ Huw *gcu m Q 4) B E- -44'd - b.D I.
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