Clinical Genetics 1977: 12: 275-284
Further delineation of the supernumerary chromosome in the Cat-Eye Syndrome K. E. TOOMEY, T. MOHANDAS, J. LEISTI,G . SZALAY':' A N D hf. M.
KABACK
Departments of Pediatrics and Medicine, U.C.L.A. School of Medicine, Division of Medical Genetics, Harbor General Hospital, Torrance, and *Southern California Permanente, Medical Group, Harbor City, California, U.S.A. A clinical diagnosis of the Cat-Eye Syndrome (CES) was made in a female child with anal stenosis, congenital heart disease, bilateral preauricular skin tags and coloboma of the right fundus. The karyotype was 46XX/47XX, +mar. Q-banding revealed the marker chromosome to be metacentric and comparable in size to that of a G-group chromosome. One arm had brightly fluorescent satellites while the other exhibited a fluorescent polymorphism similar to the short arm of a D- or G-group chromosome. Chromosome annlysis from blood cultures obtained from parents and three sibs did not demonstrate the presence of the marker chromosome. Comparison of the fluorescent polymorphisms revealed that the satellites on the marker were comparable in size and brightness to those of the maternal chromosome 22. C-banding demonstrated the marker to be dicentric. While there has been much speculation on the origin of the Cat-Eye Chromosome (CEC) based on clinical features in common with the trisomy 22 syndrome, autoradiographic studies and the general appearance of the marker, this case provides definitive evidence for the involvement of chromosome 22 in the origin of the marker chromosome. This chromosome is interpreted as the product of a Kobertsonian translocation between the short arm and satellites of chromosome 22 and the short arm of another D- or G-group chromosome, most likely 13. Thus, the karyotype of the patient is 46XX/47XX, t(?13;22) (?13pteri?l3ql1::22qll+22pter). Reinvestigation of patients with CES utilizing heritable polymorphisms may better elucidate the specific nature of the marker, and further delineate a possible basis for the heterogeneity of the disorder.
T h e Cat-Eye Syndrome, consisting of ocular coloboma, anal atresia, preauricular tags o r pits a n d o t h e r congenital anomalies was first described by H a a b (1878), and has been associated with a supernumerary chromosome since t h e report of Schachenmann el al. (1965). To date, no workers have succeeded in cytogenetically determining the origin of t h e small m a r k e r chromosome. We have studied a patient with the Cat-Eye Syndrome (CES) a n d a super-
numerary chromosome (CEC), (abbreviations after Buhler et al. (1972)) in which Q- a n d C-chromosome banding results suggest a definite origin for the m a r k e r chromosome.
Case Report
J.C., a 3500 g, 48 cm female, w a s born to a 42-year-old father and 37-year-old mother after a n uneventful 40-week gestation. Deliv-
276
TOOMEY, MOHANDAS, L E I S T I . SZALAY AND KABACK
ery was spontaneous and vaginal. The only anomaly noted at birth was bilateral preauricular skin tags. Readmitted at 5 weeks of age for failure to thrive, the baby was noted to have rectal stenosis and a harsh pansystolic murmur compatible with a ventricular septa1 defect (VSD) of minimal hemodynamic significance. The anal problem responded to daily digital dilatation. An intravenous pyelogram and barium enema were normal. Subsequently, she has thrived. At 3 months of age bilateral hip clicks were detected. The dislocation responded to appropriate casting. The VSD closed spontaneously between the fifth and seventh years. Development proceeded as follows: height and weight: 10th percentile; head circumference: 50th percentile. She sat at 13 to 14 months, and walked at
19-20 months. Her social and language development was normal. She entered the first grade at the appropriate age and currently is said to be an excellent student. When seen at 7-% years of age (Fig. l a , b), the following were noted: weight 19.8 kg (10th percentile), height 119 cm (10th percentile), OFC 50.5 cm (50th percentile), U/L 0.94. She was a pleasant, bright, outgoing black child. She had large protruding ears with bilateral preauricular sinuses, and scars at the site of the removed appendages. There was an inferior coloboma of the right fundus, an alternating esotropia and ptosis of the left lid. There was mild microphthalmos and hypertelorism, with the inner canthal distance = 37 mm, the interpupillary = 63 mm and the outer orbital = 87 mm. The palate was highly arched.
Fig. l a . Front view of patient at age 7-'/~. b. Side view of patient at a g e 7-'/2.
SUPERNUMERARY CHROMOSOME IN CAT-EYE SYNDROME
277
Fig. 2. Composite of D- and G-group chromosomes of proband's father, a; mother, b; and patient, c with marker chromosome. Three different cells are shown in each case.
There was no cardiac murmur and the remainder of the examination was within norma1 limits. Radiologic examination revealed spina bifida occulta of L4-S1 and incomplete fusion of C7 and T1. The family history was unremarkable, with the exception of a maternal cousin who was said to have Down
syndrome. The patient had three sibs, two males and one female, who were normal. Both parents were in good health. Cytogenetic Findings
Chromosome analysis of the patient was
278
TOOMEY, MOHANDAS, LEISTI, SZALAY AND KABACK
Fig. 3. Partial C-banded metaphase. Marker chromosome is seen as a dicentric (arrow).
done on 72-hour phytohemagglutinin stimd a t e d peripheral blood cultures. Conventional Giemsa staining revealed the presence of an extra marker chromosome in 7 7 of 93 (82 %) cells examined. T h e marker chromosome appeared to have satellites o n one end, and was about the same size as a G-group chromosome. Q-banding studies (Caspersson et al. 1970) revealed bright satellites and stalks on one end of the marker chromosome and a fluorescent region resembling the short a r m of a D- or G-group chromosome at the other end (Fig. 2). C-banding technique (Arrighi & Hsu 1971) demonstrated that the marker chromosome had two closely apposed C bands (Fig. 3). C-banding also produced dark staining of the satellites. Thirty metaphases from peripheral blood cultures on each parent were examined and found to be normal. Chromosome analyses from peripheral blood cultures done o n two brothers and one sister of the proband revealed normal karyotypes. A comparison of the Q-banding patterns of the D- and G group chromosomes of the father, mother
and the proband (including the marker chromosome) i s illustrated in Figure 2. T h e partial karyotypes are from three different cells in each case. T h e satellites on the marker chromosome show a striking resemblance to those o n the maternal chromosome 22, in both size and intensity. These findings strongly suggest that the marker chromosome is derived from a Robertsonian translocation involving the satellites, short arms and centromere of the maternal chromosome 22 and the centromere and short arm of another acrocentric chromosome. Comparison of the niorphology and brightness of the marker with Dand G-group chromosomes suggests that a maternal chromosome 13 is probably the second chromosome involved in this rearrangement. Discussion
Chromosome banding techniques have demonstrated several chromosomal polymorphisms in the human complement. There now is evidence that the polymorphisms ob-
SUPERNUMERARY CHROMOSOME IN CAT-EYE SYNDROME
served with Q-banding techniques (Q-polymorphisms) are heritable (Sekhon & Sly 1975, Robinson et al. 1976). The heritable nature of the variations in size and shape of the short arms, stalks and satellites of the acrocentric chromosomes was recognized in the pre-banding era (Leisti 1971). We have utilized the bright satellites on a maternal chromosome 22 to show that the supernumerary marker chromosome in our patient with CES is derived from the centromere, short arm and satellites of chromosome 22 and the centromere and short arm of another acrocentric chromosome, probably chromosome 13. I t is likely that this translocation originated in the maternal oocyte and that the mosaicism observed in the proband results from the probable loss of this marker chromosome due to mitotic irregularities. Mosaicism of a n extra small bisatellited chromosome with possible meiotic origin has been reported previously (Van Dyke et al. 1976). T h e C-banding pattern of the marker chromosome in o u r patient shows two bands, suggesting the presence of two centromeres. In some cases, Robertsonian translocations involving the long arms (Niebuhr 1972, Daniel & Lam-Po-Tang 1976) and short arms (Van Dyke et al. 1976) of D - and G-group chromosome have been shown to have two C-band regions. It has been hypothesized that the two centromeres in these cases may act as a single unit because of their proximity (Niebuhr 1972, Hsu et al. 197.5). Previous attempts to identify the C E C using chromosome banding techniques (Gerald et al. 1972, Petit 1973, DeChieri et al. 1974, Cory & Jamison 1974 and Kunze ct al. 1975), have yielded only suggestive evidence for the involvement of chromosome 22. In addition, the clinical similarity of the CES to the appearance of patients found to be trisomic for all or part of chromosome 22 (trisomy 22 syndrome) has
279
been commented o n by numerous authors, and it has been suggested that an abnormality involving chromosome 22 may play a role in the CES. T h e clinical features (Table 1) which these syndromes share are hypertelorism, preauricular pits and tags, congenital hip dislocation, heart and renal anomalies. The mental retardation seen in the T 2 2 syndrome is usually more severe than that encountered in CES, if seen at all. In addition, ocular coloboma, cleft lip and palate and anal atresia serve to distinguish the two syndromes. T h e CEC was present in 83 % of the cells of our patient, but not in her parents or three normal sibs. This probably represents a sufficient degree of mosaicism to cause the phenotypic alterations of the CES. A mild degree of mosaicism (8 % in each case) was seen in three relatives of one of Schachenmann's patients (Schachenmann et al. 1965) all of whom were phenotypically normal. T h e mother of Schachenmann's patient had the extra fragment in all cells examined and showed some features of the Tab!e 1 Comparison of clinical features of the Cat Eye Syndrome" and trisomy 22*' T22
Mental retardation Microcephaly Hypertelorism Antimongoloid slant Beaked nose Increased philtrum length Cleft palate Micrognathia Low-set rotated ears Preauricular tags or sinuses Prominent antihelix Deformed upper extremity Hip abnormality Congenital heart disease Urogenital tract anomalies Anal atresia Coloboma Microphthalmia * Based on 28 cases * * From Hsu Ei Hirschhorn (1977)
+ + + + + + + + + + + + + + + -
CES
+ + + +
-
+ + + + + + + +
280
TOOMEY, MOHANDAS, LEISTI, SZALAY AND KABACK
Table 2 Incidence of features in Cat Eye Syndrome complete
(N = 15)
Coloboma Microphthalmia Depressed nasal bridge Hypertelorism Epicanthus Preauricular tags Preauricular pits Heart defect Hip dislocation Renal anomalies Anal stenosis or atresia Recto-vaginallurethral fistula Mental retardation Average birth weight Sex ratio (M:F) Average maternal age Average paternal age Other defects
15/15‘ 415 z2 818
112 11/11 11/11
Incomplete (N = 13)
5112 3/7 314 515 216
5110 3285 5:lO 31.4 33.6
6110 518 517 112 7110 9113 415 415 2925 7:7 28.5 32.4
616
818
417 317
811 1 15115 718
of cases in which feature mentioned. Cases detailed in Tables 3 and 4.
* Number positive observationslnurnber
CES. The father and sister of one of Gerald’s patients (Gerald et al. 1972) were mosaics for the marker (28 and 44 % of their cells positive for the marker, respectively) and were also apparently normal. The mother of Darby’s patient (Darby & Hughes 1971) had the marker in 50 % of her cells and was normal. In a recent review, Hsu & Hirschhorn (1977) categorized cases of CES with an extra chromosome into complete and incomplete forms, based on the presence of one or both of the two major features of the syndrome, coloboma and anal atresia. It might be noted that each of their “complete” cases also possessed preauricular tags or sinuses, so that these three features appeared together consistently in the complete form of the syndrome. Our survey of the literature yielded 28 cases of the CES with documentation of a supernumerary marker chromosome. Four-
teen of these and the present case would fall into Hsu’s “complete” form, while fourteen would be “incomplete.” Table 2 summarizes the rate of occurrence of the features of the CES in the 28 cases from the literature and in the present case. In addition, there is the family of Biihler (Biihler et al. 1972), in which a 22q- chromosome segregates as part of a probable balanced translocation, leading to partial trisomy 22 in an individual who has been considered by some reviewers to have the CES. Finally, there are cases reported as CES but without cytogenetic evidence of a marker chromosome or other chromosomal aberration (Neu et al. 1970, Franklin & Parslow 1972). Whether we are dealing with variable expressivity of a common genetic defect, or whether the CES exists as a heterogeneous disorder remains to be determined. The following possibilities are offered for consideration: 1) Mosaicism, which has been shown in the present case and others, may remain undetected. It is interesting, however, that mosaicism has not been correlated with the apparent degree of expression of the syndrome. 2) While clinical and cytogenetic evidence seem to indicate that chromosome 22 is most consistently involved in the make-up of the marker, this has not been well documented in any other cases, Also lacking, has been unquestionable evidence for the involvement of a second specific chromosome in the composition of the marker, Portions of different D- and G-group chromosomes in addition to 22 may be involved in the constitution of the marker chromosome and may thereby account for the variability of the syndrome. 3) Finally, there may exist a non-chromosoma1 basis for the CES, and even in the so-called familial cases, the various features (i.e., coloboma, anal atresia, preauricular
+I+
-
+/+
+
+
+
Other defects
+
+
26/28
F
F 29/
3150
+ +
-
2400
+
+
+
+
37/37
M
3200
+ + +
+I+
+
M
+
+
+I+
-
+
+
7
F
+
+
+ +
+
I+
8
+
F
+
+ -
-
-
+I+
9
+
M
-
-
+
-
-
+I
-
+
+I+
10
+
32/34
F
2665
-
+
-
-
+
+I+
11
19127
M
+
+
-
-
+
+
-
14
34142
F
301
F
28502900
+
+
13
12
References: Cases (1) Ishmael 8 Lawrence (1965); (2) DeChieri et al. (1974); (3) Gerald et al. (1972); (4) Zellweger et al. (1972); (5) Curcio (1967); (6) Beyer et al. (1968); (7-8) Ballesta (1973); (9) Schachenmann et al. (1965); (10) Noel 8 Quack (1970); (11) Ginsburg et al. (1968); (12-14) Gerald et al. (1968).
32/40
M
M
24/21
3180
2800
+
+
t-
-
-
22l30
M
3180
+ + +
+
+
+I
-
+
+I
+
-
-
+
-
6
-
5
+ -
Mat./pat. age
Sex
Birth weight
Mental retardation
Recto vag./ure. fistula
Anal stenosis/atresia
Renal anomalies
Hip dislocation
Heart defect
Preauricular pits (RIL)
Preauricular tags (RIL)
Epicanthus
Hypertelorism
+
-
+ + -
-
-
-
+
-
Microphthalmia
-
+/+
-
4
Coloboma (R/L)
3
2
1
Clinical feature
Depressed nasal bridge
Table 3 Cases of Cat Eye Syndrome (incomplete) with marker chromosome
Further delineation of the supernumerary chromosome in the Cat-Eye Syndrome K. E. TOOMEY, T. MOHANDAS, J. LEISTI,G . SZALAY':' A N D hf. M.
KABACK
Departments of Pediatrics and Medicine, U.C.L.A. School of Medicine, Division of Medical Genetics, Harbor General Hospital, Torrance, and *Southern California Permanente, Medical Group, Harbor City, California, U.S.A. A clinical diagnosis of the Cat-Eye Syndrome (CES) was made in a female child with anal stenosis, congenital heart disease, bilateral preauricular skin tags and coloboma of the right fundus. The karyotype was 46XX/47XX, +mar. Q-banding revealed the marker chromosome to be metacentric and comparable in size to that of a G-group chromosome. One arm had brightly fluorescent satellites while the other exhibited a fluorescent polymorphism similar to the short arm of a D- or G-group chromosome. Chromosome annlysis from blood cultures obtained from parents and three sibs did not demonstrate the presence of the marker chromosome. Comparison of the fluorescent polymorphisms revealed that the satellites on the marker were comparable in size and brightness to those of the maternal chromosome 22. C-banding demonstrated the marker to be dicentric. While there has been much speculation on the origin of the Cat-Eye Chromosome (CEC) based on clinical features in common with the trisomy 22 syndrome, autoradiographic studies and the general appearance of the marker, this case provides definitive evidence for the involvement of chromosome 22 in the origin of the marker chromosome. This chromosome is interpreted as the product of a Kobertsonian translocation between the short arm and satellites of chromosome 22 and the short arm of another D- or G-group chromosome, most likely 13. Thus, the karyotype of the patient is 46XX/47XX, t(?13;22) (?13pteri?l3ql1::22qll+22pter). Reinvestigation of patients with CES utilizing heritable polymorphisms may better elucidate the specific nature of the marker, and further delineate a possible basis for the heterogeneity of the disorder.
T h e Cat-Eye Syndrome, consisting of ocular coloboma, anal atresia, preauricular tags o r pits a n d o t h e r congenital anomalies was first described by H a a b (1878), and has been associated with a supernumerary chromosome since t h e report of Schachenmann el al. (1965). To date, no workers have succeeded in cytogenetically determining the origin of t h e small m a r k e r chromosome. We have studied a patient with the Cat-Eye Syndrome (CES) a n d a super-
numerary chromosome (CEC), (abbreviations after Buhler et al. (1972)) in which Q- a n d C-chromosome banding results suggest a definite origin for the m a r k e r chromosome.
Case Report
J.C., a 3500 g, 48 cm female, w a s born to a 42-year-old father and 37-year-old mother after a n uneventful 40-week gestation. Deliv-
276
TOOMEY, MOHANDAS, L E I S T I . SZALAY AND KABACK
ery was spontaneous and vaginal. The only anomaly noted at birth was bilateral preauricular skin tags. Readmitted at 5 weeks of age for failure to thrive, the baby was noted to have rectal stenosis and a harsh pansystolic murmur compatible with a ventricular septa1 defect (VSD) of minimal hemodynamic significance. The anal problem responded to daily digital dilatation. An intravenous pyelogram and barium enema were normal. Subsequently, she has thrived. At 3 months of age bilateral hip clicks were detected. The dislocation responded to appropriate casting. The VSD closed spontaneously between the fifth and seventh years. Development proceeded as follows: height and weight: 10th percentile; head circumference: 50th percentile. She sat at 13 to 14 months, and walked at
19-20 months. Her social and language development was normal. She entered the first grade at the appropriate age and currently is said to be an excellent student. When seen at 7-% years of age (Fig. l a , b), the following were noted: weight 19.8 kg (10th percentile), height 119 cm (10th percentile), OFC 50.5 cm (50th percentile), U/L 0.94. She was a pleasant, bright, outgoing black child. She had large protruding ears with bilateral preauricular sinuses, and scars at the site of the removed appendages. There was an inferior coloboma of the right fundus, an alternating esotropia and ptosis of the left lid. There was mild microphthalmos and hypertelorism, with the inner canthal distance = 37 mm, the interpupillary = 63 mm and the outer orbital = 87 mm. The palate was highly arched.
Fig. l a . Front view of patient at age 7-'/~. b. Side view of patient at a g e 7-'/2.
SUPERNUMERARY CHROMOSOME IN CAT-EYE SYNDROME
277
Fig. 2. Composite of D- and G-group chromosomes of proband's father, a; mother, b; and patient, c with marker chromosome. Three different cells are shown in each case.
There was no cardiac murmur and the remainder of the examination was within norma1 limits. Radiologic examination revealed spina bifida occulta of L4-S1 and incomplete fusion of C7 and T1. The family history was unremarkable, with the exception of a maternal cousin who was said to have Down
syndrome. The patient had three sibs, two males and one female, who were normal. Both parents were in good health. Cytogenetic Findings
Chromosome analysis of the patient was
278
TOOMEY, MOHANDAS, LEISTI, SZALAY AND KABACK
Fig. 3. Partial C-banded metaphase. Marker chromosome is seen as a dicentric (arrow).
done on 72-hour phytohemagglutinin stimd a t e d peripheral blood cultures. Conventional Giemsa staining revealed the presence of an extra marker chromosome in 7 7 of 93 (82 %) cells examined. T h e marker chromosome appeared to have satellites o n one end, and was about the same size as a G-group chromosome. Q-banding studies (Caspersson et al. 1970) revealed bright satellites and stalks on one end of the marker chromosome and a fluorescent region resembling the short a r m of a D- or G-group chromosome at the other end (Fig. 2). C-banding technique (Arrighi & Hsu 1971) demonstrated that the marker chromosome had two closely apposed C bands (Fig. 3). C-banding also produced dark staining of the satellites. Thirty metaphases from peripheral blood cultures on each parent were examined and found to be normal. Chromosome analyses from peripheral blood cultures done o n two brothers and one sister of the proband revealed normal karyotypes. A comparison of the Q-banding patterns of the D- and G group chromosomes of the father, mother
and the proband (including the marker chromosome) i s illustrated in Figure 2. T h e partial karyotypes are from three different cells in each case. T h e satellites on the marker chromosome show a striking resemblance to those o n the maternal chromosome 22, in both size and intensity. These findings strongly suggest that the marker chromosome is derived from a Robertsonian translocation involving the satellites, short arms and centromere of the maternal chromosome 22 and the centromere and short arm of another acrocentric chromosome. Comparison of the niorphology and brightness of the marker with Dand G-group chromosomes suggests that a maternal chromosome 13 is probably the second chromosome involved in this rearrangement. Discussion
Chromosome banding techniques have demonstrated several chromosomal polymorphisms in the human complement. There now is evidence that the polymorphisms ob-
SUPERNUMERARY CHROMOSOME IN CAT-EYE SYNDROME
served with Q-banding techniques (Q-polymorphisms) are heritable (Sekhon & Sly 1975, Robinson et al. 1976). The heritable nature of the variations in size and shape of the short arms, stalks and satellites of the acrocentric chromosomes was recognized in the pre-banding era (Leisti 1971). We have utilized the bright satellites on a maternal chromosome 22 to show that the supernumerary marker chromosome in our patient with CES is derived from the centromere, short arm and satellites of chromosome 22 and the centromere and short arm of another acrocentric chromosome, probably chromosome 13. I t is likely that this translocation originated in the maternal oocyte and that the mosaicism observed in the proband results from the probable loss of this marker chromosome due to mitotic irregularities. Mosaicism of a n extra small bisatellited chromosome with possible meiotic origin has been reported previously (Van Dyke et al. 1976). T h e C-banding pattern of the marker chromosome in o u r patient shows two bands, suggesting the presence of two centromeres. In some cases, Robertsonian translocations involving the long arms (Niebuhr 1972, Daniel & Lam-Po-Tang 1976) and short arms (Van Dyke et al. 1976) of D - and G-group chromosome have been shown to have two C-band regions. It has been hypothesized that the two centromeres in these cases may act as a single unit because of their proximity (Niebuhr 1972, Hsu et al. 197.5). Previous attempts to identify the C E C using chromosome banding techniques (Gerald et al. 1972, Petit 1973, DeChieri et al. 1974, Cory & Jamison 1974 and Kunze ct al. 1975), have yielded only suggestive evidence for the involvement of chromosome 22. In addition, the clinical similarity of the CES to the appearance of patients found to be trisomic for all or part of chromosome 22 (trisomy 22 syndrome) has
279
been commented o n by numerous authors, and it has been suggested that an abnormality involving chromosome 22 may play a role in the CES. T h e clinical features (Table 1) which these syndromes share are hypertelorism, preauricular pits and tags, congenital hip dislocation, heart and renal anomalies. The mental retardation seen in the T 2 2 syndrome is usually more severe than that encountered in CES, if seen at all. In addition, ocular coloboma, cleft lip and palate and anal atresia serve to distinguish the two syndromes. T h e CEC was present in 83 % of the cells of our patient, but not in her parents or three normal sibs. This probably represents a sufficient degree of mosaicism to cause the phenotypic alterations of the CES. A mild degree of mosaicism (8 % in each case) was seen in three relatives of one of Schachenmann's patients (Schachenmann et al. 1965) all of whom were phenotypically normal. T h e mother of Schachenmann's patient had the extra fragment in all cells examined and showed some features of the Tab!e 1 Comparison of clinical features of the Cat Eye Syndrome" and trisomy 22*' T22
Mental retardation Microcephaly Hypertelorism Antimongoloid slant Beaked nose Increased philtrum length Cleft palate Micrognathia Low-set rotated ears Preauricular tags or sinuses Prominent antihelix Deformed upper extremity Hip abnormality Congenital heart disease Urogenital tract anomalies Anal atresia Coloboma Microphthalmia * Based on 28 cases * * From Hsu Ei Hirschhorn (1977)
+ + + + + + + + + + + + + + + -
CES
+ + + +
-
+ + + + + + + +
280
TOOMEY, MOHANDAS, LEISTI, SZALAY AND KABACK
Table 2 Incidence of features in Cat Eye Syndrome complete
(N = 15)
Coloboma Microphthalmia Depressed nasal bridge Hypertelorism Epicanthus Preauricular tags Preauricular pits Heart defect Hip dislocation Renal anomalies Anal stenosis or atresia Recto-vaginallurethral fistula Mental retardation Average birth weight Sex ratio (M:F) Average maternal age Average paternal age Other defects
15/15‘ 415 z2 818
112 11/11 11/11
Incomplete (N = 13)
5112 3/7 314 515 216
5110 3285 5:lO 31.4 33.6
6110 518 517 112 7110 9113 415 415 2925 7:7 28.5 32.4
616
818
417 317
811 1 15115 718
of cases in which feature mentioned. Cases detailed in Tables 3 and 4.
* Number positive observationslnurnber
CES. The father and sister of one of Gerald’s patients (Gerald et al. 1972) were mosaics for the marker (28 and 44 % of their cells positive for the marker, respectively) and were also apparently normal. The mother of Darby’s patient (Darby & Hughes 1971) had the marker in 50 % of her cells and was normal. In a recent review, Hsu & Hirschhorn (1977) categorized cases of CES with an extra chromosome into complete and incomplete forms, based on the presence of one or both of the two major features of the syndrome, coloboma and anal atresia. It might be noted that each of their “complete” cases also possessed preauricular tags or sinuses, so that these three features appeared together consistently in the complete form of the syndrome. Our survey of the literature yielded 28 cases of the CES with documentation of a supernumerary marker chromosome. Four-
teen of these and the present case would fall into Hsu’s “complete” form, while fourteen would be “incomplete.” Table 2 summarizes the rate of occurrence of the features of the CES in the 28 cases from the literature and in the present case. In addition, there is the family of Biihler (Biihler et al. 1972), in which a 22q- chromosome segregates as part of a probable balanced translocation, leading to partial trisomy 22 in an individual who has been considered by some reviewers to have the CES. Finally, there are cases reported as CES but without cytogenetic evidence of a marker chromosome or other chromosomal aberration (Neu et al. 1970, Franklin & Parslow 1972). Whether we are dealing with variable expressivity of a common genetic defect, or whether the CES exists as a heterogeneous disorder remains to be determined. The following possibilities are offered for consideration: 1) Mosaicism, which has been shown in the present case and others, may remain undetected. It is interesting, however, that mosaicism has not been correlated with the apparent degree of expression of the syndrome. 2) While clinical and cytogenetic evidence seem to indicate that chromosome 22 is most consistently involved in the make-up of the marker, this has not been well documented in any other cases, Also lacking, has been unquestionable evidence for the involvement of a second specific chromosome in the composition of the marker, Portions of different D- and G-group chromosomes in addition to 22 may be involved in the constitution of the marker chromosome and may thereby account for the variability of the syndrome. 3) Finally, there may exist a non-chromosoma1 basis for the CES, and even in the so-called familial cases, the various features (i.e., coloboma, anal atresia, preauricular
+I+
-
+/+
+
+
+
Other defects
+
+
26/28
F
F 29/
3150
+ +
-
2400
+
+
+
+
37/37
M
3200
+ + +
+I+
+
M
+
+
+I+
-
+
+
7
F
+
+
+ +
+
I+
8
+
F
+
+ -
-
-
+I+
9
+
M
-
-
+
-
-
+I
-
+
+I+
10
+
32/34
F
2665
-
+
-
-
+
+I+
11
19127
M
+
+
-
-
+
+
-
14
34142
F
301
F
28502900
+
+
13
12
References: Cases (1) Ishmael 8 Lawrence (1965); (2) DeChieri et al. (1974); (3) Gerald et al. (1972); (4) Zellweger et al. (1972); (5) Curcio (1967); (6) Beyer et al. (1968); (7-8) Ballesta (1973); (9) Schachenmann et al. (1965); (10) Noel 8 Quack (1970); (11) Ginsburg et al. (1968); (12-14) Gerald et al. (1968).
32/40
M
M
24/21
3180
2800
+
+
t-
-
-
22l30
M
3180
+ + +
+
+
+I
-
+
+I
+
-
-
+
-
6
-
5
+ -
Mat./pat. age
Sex
Birth weight
Mental retardation
Recto vag./ure. fistula
Anal stenosis/atresia
Renal anomalies
Hip dislocation
Heart defect
Preauricular pits (RIL)
Preauricular tags (RIL)
Epicanthus
Hypertelorism
+
-
+ + -
-
-
-
+
-
Microphthalmia
-
+/+
-
4
Coloboma (R/L)
3
2
1
Clinical feature
Depressed nasal bridge
Table 3 Cases of Cat Eye Syndrome (incomplete) with marker chromosome
