American Journal of Medical Genetics 39:204-206 (1991)
Interstitial Deletion de1(2)(q24q31)With a Phenotype Similar to de1(2)(q31q33) Christine Wamsler, Bertram Muller, Gabriele Freyberger, and Michael Schmid Department of Human Genetics, University of Wiirzburg, Koellikerstr. 2, Wiirzburg, Germany tion and microcephaly. Body weight, head circumference, and length were all below the third centile. Notable findings included low set, abnormal ears, narrow palpebral fissures with a n antimongoloid slant (Fig. 1). Hypotelorism, ptosis, a large beaked nose, receding chin, receding forehead, and a high arched palate were also present. The hands showed a simian crease bilatKEY WORDS: deletion 2q, chromosomes, erally, camptodactyly, clinodactyly, and brachymesocongenital anomalies phalangism. In addition there was a bilateral sandle gap of the toes and skin syndactyly between toes IV and V. Severe statomotor and psychomotor deficit was obvious. INTRODUCTION Muscle tone of the limbs was normal; muscles of the Eight cases of de1(2)(q31q33)have been described in trunk showed mild hypotonus. The patient was able to the literature [Taysi et al., 1981; Al-Awadi e t al., 1983; sit and stand. Walking without support was not possiBuchanan et al., 1983; F’ranceschini et al., 1983; Young ble. At age 18months generalized seizures without EEG et al., 1983; Sanchez and Pantano, 1984; Benson et al., or CT findings developed. On physical examination 1986; Ramer et al., 19891. An additional 14 cases with there were no indications of any cardiac defect. ECG and interstitial deletions of 2q other than de1(2)(q31q33) auscultation were normal. Family history was negative. have been reported [Warter e t al., 1976; F’ryns et al., CYTOGENETIC STUDIES 1977; McConnell et al., 1980; Shabtai et al., 1980; Pai et al., 1983; Antich et al., 1981; Bernar et al., 1984; SanGTG and RHG banding were performed according to chez and Pantano, 1984; Markovich et al., 1985; Benson standard procedures. The karyotype of the patient was et al., 1986, Kiyoshi et al., 1988; Glass et al., 1989; Halal found to be 46,XX, - 2, + 2pter--*q24::q3l-+qter (Fig. 2). et al., 19891. Parents and sibs had normal chromosomes. A review of the phenotype-karyotype correlations in individuals with interstitial deletions of the long arm of chromosome 2 has recently been reported by Ramer et al. [19891.We report on a girl with del(2Xq24q311,whose phenotype shows considerable similarity to the de1(2)(q31q33)phenotype.
A 33/iz-year-oldgirl with multiple anomalies is reported. An interstitial deletion de1(2)(q24q31) was demonstrated. There is consic‘ ,rable overlap of symptoms in cases with de1(2)(q31q33),which are reviewed.
CLINICAL REPORT The patient, a female, was born as the third child of healthy, unrelated parents after 42 weeks of gestation. Pregnancy and delivery were uneventful. At this time the mother was 32 and the father 38 years old. Apgar scores were 8i8i9 (1/5/10 min). Birth weight was 3,200 g (25th centile), head circumference 33 cm (10th centile), and length 50 cm (50th centile). At age 6 months the patient was first hospitalized because of growth retarda-
Received for publication December 7, 1990; revision received April 14, 1990. Address reprint requests to Dr. Michael Schmid, Department of Human Genetics, University of Wiirzburg, Koellikerstr. 2, D-8700 Wiirzburg, Germany.
0 1991 Wiley-Liss, Inc.
Fig. 1. The patient at age
33/i2
years.
Interstitial Deletion del(2Mq24q31)
205
Fig. 2. (a) Two G-banded and (b)one R-banded chromosome pairs 2 from the patient showing the de1(21(q24q311.The lines between the homologues indicate the deleted segment. (c) Diagrammatic G-band drawings showing the breakpoints a t 2q24 and 2q31 involved in the deletion.
TABLE I. Features of Individuals With Deletions of Similar Segments McConnell et al. [1980] q22q31 Birth weight ~ 5 t centile h Growth failure Developmental delayimental retardation Cleft palate Microcephaly Microphthalmia Cataract Ptosis Micrognathia Abnormal ears Heart defect Sandle gap
+ + Died at 1 day +
COMPUTERAIDED SYNDROME DIAGNOSIS Independent from cytogenetic analysis, a computerized search with the London dysmorphology database [Winter et al., 19841 supplemented by the chromosome database [Brandl and Grimm, 19871 was done. A variety of searches yielded a list of possible diagnoses strongly biased toward a chromosomal aberration. A deletion of chromosome 2q was present repeatedly among the list of possible diagnoses. DISCUSSION It seems to be reasonable to divide the cases with interstitial deletion in the long arm of chromosome 2 into 2 groups. The first group with breakpoints in q31 and q33 is characterized by a specific phenotype that is given by Ramer et al. [19891 in their review. Apart from manifestations common to most cases of autosomal deletions such as low birth weight and growth and mental retardation, more than a half of the cases present with microcephaly, microphthalmia, micrognathia, abnormal ears, and camptodactyly. The second group consists of cases of interstitial deletion of other segments of 2q. Although, in all those
-
-
+ + + + +
Case and deleted segment Shabtei e t al. [1982] q23q34
Present case
-
-
+ + + + + + + + ++
+ + + ~
~
-
+ + ++
patients, different segments are involved some similarity in phenotype can be observed. Beside the common findings in autosomal deletions which we noted above, more than half of the cases showed micrognathia, abnormal ears, and cleft palate. In the present case the breakpoints were in q24-31. Apart from microphthalmia, all main signs of group one were observed. Two of the 3 main manifestations in the second group were present but there is no cleft palate in our patient (Table I).
REFERENCES Al-Awadi SA, Farag TI, Naguib K, Teebi A, Cuschieri A, Al-Othman S, Sundareshan TS, (1983): Interstitial deletion of the long arm of chromosome 2: de1(2)(q31q33). Case reports. J Med Genet 20: 464-465. Antich J, Carbonell X, Clusellas N (1981):De Novo interstitial deletion of the long arm of chromosome 2 in a malformed newborn-karyotype: 46,XY,de1(2)(q12q14).Clin Genet 19:489-491. Benson K, Gordon M, Wassman ER, Chung T (1986):Interstitial deletion of the long arm of chromosome 2 in a malformed infant with karyotype 46,XX,de1(2)(q31q331.Am J Med Genet 25405-411. Bernar J, Sparkes R, Allensworth S (1985):Interstitial deletion 2q24.3: Case report with high resolution banding. J Med Genet 22: 226-228.
206
Wamsler et al.
Brand1 J, Grimm T (1987): A chromosome supplement to the London dysmorphology database. J Med Genet 24:497-498. Buchanan P, Rhodes RL, Stevebson CE (1983): Interstitial deletion 2q31-33. Am J Med Genet 15:121-126. Ranceschini P, Silengo NC, Davi G, Bianco R, Biagioli M (1983): Interstitial deletion of the long arm of chromosome Z(q31-33) in a girl with multiple anomalies and mental retardation. Hum Genet 64:98. Fkyns JP, Van Bosstraeten B, Malbrain H, Van der Berghe H (1977): Interstitial deletion of the long arm of chromosome 2 in a polymalformed newborn-karyotype: 46,XX,de1(2)(21;24).Hum Genet 39:233-238. Glass IA, Swindlehurst CA, Aitken DA, Mc Crea W (1989):Interstitial deletion of the long arm of chromosome 2 with normal levels of isocitrate dehydrogenase. J Med Genet 26:127-130. Gorski JL, Kiyne M, Uhlmann W, Loeffler K, Glover TH.W (1989): Interstitial deletion of 2 (q33q36)in a child with congenital abnormalities. J Med Genet 26:204-206. Halal F, Vekemans M, Vazken M, Der Kaloustian (1989):A presumptive translocation lp;2q resulting in duplication l p and deletion 2q. Am J Med Genet 32:376-379. Kiyoshi M, Tsutomu Y, Nobuaki 0 (1988):Interstitial deletion 2q32.1q34 in a child with half normal activity of ribulose 5-phosphatase 3-empimerase (RPE). J Med Genet 25:850-851. Marcovic S, Krstic M, Sulovic V, Radojkocic 2, Adzic S (1985):Interstitial deletion of chromosome 2. J Med Genet 22154-157. McConnell TS, Kornfield M, McClellan G, Aase J (1980):Partial dele-
tion of chromosome 2 mimicking a phenotype of trisomy 18: Case report with autopsy. Hum Pathol 11:202-205. Pai GS, Rogers J F , Sommer A (1983): Identical multiple congenital anomaliesimental retardation (MCAIMR) syndrome due to del (2)(q32) in two sisters with intrachromosomal insertional translocation in their father. Am J Med Genet 14:189-195. Ramer JC, Ladda RL, Frankel CA, Beckford A (1989): A review of phenotype-karyotype correlations in individuals with interstitial deletion of the long arm of chromosome 2. Am J Med Genet 32:359-363. Sanchez J, Pantano AM (1984): A case of deletion 2q35-qter and a peculiar phenotype. J Med Genet 21:147-149. Shabtai F, Klar D, Halbrecht I (1982): Patial deletion of chromosome 2. Delineable syndrome of deletion 2(q23-q31) Ann Genet 25: 156-158. Taysi K, Dengler DR, Jones LA, Heersma J R (1981):Interstitial deletion of the long arm of chromosome 2. Case report and review of literature. Ann Genet 24:245-247. Warter S, Lausecker C, Pennerath A (1976):Etudes chromosomique et clinique d’une fillette porteuse d’une deletion (2)(q34q36).Hum Genet 32:225-227. Winter RM, Baraitser M, Douglas JM (1984):A computerised database for the diagnosis of rare dysmorphic syndromes. J Med Genet 21:121-123. Young RS, Shapiro SD, Hansen K, Hine RK, Rainosek D, Guerra FA (1983): Deletion 2q: Two new cases with karyotypes 46,XY,de1(2) (q31q33) and 46,XX,de1(2)(q36).J Med Genet 20:199-202.
Interstitial Deletion de1(2)(q24q31)With a Phenotype Similar to de1(2)(q31q33) Christine Wamsler, Bertram Muller, Gabriele Freyberger, and Michael Schmid Department of Human Genetics, University of Wiirzburg, Koellikerstr. 2, Wiirzburg, Germany tion and microcephaly. Body weight, head circumference, and length were all below the third centile. Notable findings included low set, abnormal ears, narrow palpebral fissures with a n antimongoloid slant (Fig. 1). Hypotelorism, ptosis, a large beaked nose, receding chin, receding forehead, and a high arched palate were also present. The hands showed a simian crease bilatKEY WORDS: deletion 2q, chromosomes, erally, camptodactyly, clinodactyly, and brachymesocongenital anomalies phalangism. In addition there was a bilateral sandle gap of the toes and skin syndactyly between toes IV and V. Severe statomotor and psychomotor deficit was obvious. INTRODUCTION Muscle tone of the limbs was normal; muscles of the Eight cases of de1(2)(q31q33)have been described in trunk showed mild hypotonus. The patient was able to the literature [Taysi et al., 1981; Al-Awadi e t al., 1983; sit and stand. Walking without support was not possiBuchanan et al., 1983; F’ranceschini et al., 1983; Young ble. At age 18months generalized seizures without EEG et al., 1983; Sanchez and Pantano, 1984; Benson et al., or CT findings developed. On physical examination 1986; Ramer et al., 19891. An additional 14 cases with there were no indications of any cardiac defect. ECG and interstitial deletions of 2q other than de1(2)(q31q33) auscultation were normal. Family history was negative. have been reported [Warter e t al., 1976; F’ryns et al., CYTOGENETIC STUDIES 1977; McConnell et al., 1980; Shabtai et al., 1980; Pai et al., 1983; Antich et al., 1981; Bernar et al., 1984; SanGTG and RHG banding were performed according to chez and Pantano, 1984; Markovich et al., 1985; Benson standard procedures. The karyotype of the patient was et al., 1986, Kiyoshi et al., 1988; Glass et al., 1989; Halal found to be 46,XX, - 2, + 2pter--*q24::q3l-+qter (Fig. 2). et al., 19891. Parents and sibs had normal chromosomes. A review of the phenotype-karyotype correlations in individuals with interstitial deletions of the long arm of chromosome 2 has recently been reported by Ramer et al. [19891.We report on a girl with del(2Xq24q311,whose phenotype shows considerable similarity to the de1(2)(q31q33)phenotype.
A 33/iz-year-oldgirl with multiple anomalies is reported. An interstitial deletion de1(2)(q24q31) was demonstrated. There is consic‘ ,rable overlap of symptoms in cases with de1(2)(q31q33),which are reviewed.
CLINICAL REPORT The patient, a female, was born as the third child of healthy, unrelated parents after 42 weeks of gestation. Pregnancy and delivery were uneventful. At this time the mother was 32 and the father 38 years old. Apgar scores were 8i8i9 (1/5/10 min). Birth weight was 3,200 g (25th centile), head circumference 33 cm (10th centile), and length 50 cm (50th centile). At age 6 months the patient was first hospitalized because of growth retarda-
Received for publication December 7, 1990; revision received April 14, 1990. Address reprint requests to Dr. Michael Schmid, Department of Human Genetics, University of Wiirzburg, Koellikerstr. 2, D-8700 Wiirzburg, Germany.
0 1991 Wiley-Liss, Inc.
Fig. 1. The patient at age
33/i2
years.
Interstitial Deletion del(2Mq24q31)
205
Fig. 2. (a) Two G-banded and (b)one R-banded chromosome pairs 2 from the patient showing the de1(21(q24q311.The lines between the homologues indicate the deleted segment. (c) Diagrammatic G-band drawings showing the breakpoints a t 2q24 and 2q31 involved in the deletion.
TABLE I. Features of Individuals With Deletions of Similar Segments McConnell et al. [1980] q22q31 Birth weight ~ 5 t centile h Growth failure Developmental delayimental retardation Cleft palate Microcephaly Microphthalmia Cataract Ptosis Micrognathia Abnormal ears Heart defect Sandle gap
+ + Died at 1 day +
COMPUTERAIDED SYNDROME DIAGNOSIS Independent from cytogenetic analysis, a computerized search with the London dysmorphology database [Winter et al., 19841 supplemented by the chromosome database [Brandl and Grimm, 19871 was done. A variety of searches yielded a list of possible diagnoses strongly biased toward a chromosomal aberration. A deletion of chromosome 2q was present repeatedly among the list of possible diagnoses. DISCUSSION It seems to be reasonable to divide the cases with interstitial deletion in the long arm of chromosome 2 into 2 groups. The first group with breakpoints in q31 and q33 is characterized by a specific phenotype that is given by Ramer et al. [19891 in their review. Apart from manifestations common to most cases of autosomal deletions such as low birth weight and growth and mental retardation, more than a half of the cases present with microcephaly, microphthalmia, micrognathia, abnormal ears, and camptodactyly. The second group consists of cases of interstitial deletion of other segments of 2q. Although, in all those
-
-
+ + + + +
Case and deleted segment Shabtei e t al. [1982] q23q34
Present case
-
-
+ + + + + + + + ++
+ + + ~
~
-
+ + ++
patients, different segments are involved some similarity in phenotype can be observed. Beside the common findings in autosomal deletions which we noted above, more than half of the cases showed micrognathia, abnormal ears, and cleft palate. In the present case the breakpoints were in q24-31. Apart from microphthalmia, all main signs of group one were observed. Two of the 3 main manifestations in the second group were present but there is no cleft palate in our patient (Table I).
REFERENCES Al-Awadi SA, Farag TI, Naguib K, Teebi A, Cuschieri A, Al-Othman S, Sundareshan TS, (1983): Interstitial deletion of the long arm of chromosome 2: de1(2)(q31q33). Case reports. J Med Genet 20: 464-465. Antich J, Carbonell X, Clusellas N (1981):De Novo interstitial deletion of the long arm of chromosome 2 in a malformed newborn-karyotype: 46,XY,de1(2)(q12q14).Clin Genet 19:489-491. Benson K, Gordon M, Wassman ER, Chung T (1986):Interstitial deletion of the long arm of chromosome 2 in a malformed infant with karyotype 46,XX,de1(2)(q31q331.Am J Med Genet 25405-411. Bernar J, Sparkes R, Allensworth S (1985):Interstitial deletion 2q24.3: Case report with high resolution banding. J Med Genet 22: 226-228.
206
Wamsler et al.
Brand1 J, Grimm T (1987): A chromosome supplement to the London dysmorphology database. J Med Genet 24:497-498. Buchanan P, Rhodes RL, Stevebson CE (1983): Interstitial deletion 2q31-33. Am J Med Genet 15:121-126. Ranceschini P, Silengo NC, Davi G, Bianco R, Biagioli M (1983): Interstitial deletion of the long arm of chromosome Z(q31-33) in a girl with multiple anomalies and mental retardation. Hum Genet 64:98. Fkyns JP, Van Bosstraeten B, Malbrain H, Van der Berghe H (1977): Interstitial deletion of the long arm of chromosome 2 in a polymalformed newborn-karyotype: 46,XX,de1(2)(21;24).Hum Genet 39:233-238. Glass IA, Swindlehurst CA, Aitken DA, Mc Crea W (1989):Interstitial deletion of the long arm of chromosome 2 with normal levels of isocitrate dehydrogenase. J Med Genet 26:127-130. Gorski JL, Kiyne M, Uhlmann W, Loeffler K, Glover TH.W (1989): Interstitial deletion of 2 (q33q36)in a child with congenital abnormalities. J Med Genet 26:204-206. Halal F, Vekemans M, Vazken M, Der Kaloustian (1989):A presumptive translocation lp;2q resulting in duplication l p and deletion 2q. Am J Med Genet 32:376-379. Kiyoshi M, Tsutomu Y, Nobuaki 0 (1988):Interstitial deletion 2q32.1q34 in a child with half normal activity of ribulose 5-phosphatase 3-empimerase (RPE). J Med Genet 25:850-851. Marcovic S, Krstic M, Sulovic V, Radojkocic 2, Adzic S (1985):Interstitial deletion of chromosome 2. J Med Genet 22154-157. McConnell TS, Kornfield M, McClellan G, Aase J (1980):Partial dele-
tion of chromosome 2 mimicking a phenotype of trisomy 18: Case report with autopsy. Hum Pathol 11:202-205. Pai GS, Rogers J F , Sommer A (1983): Identical multiple congenital anomaliesimental retardation (MCAIMR) syndrome due to del (2)(q32) in two sisters with intrachromosomal insertional translocation in their father. Am J Med Genet 14:189-195. Ramer JC, Ladda RL, Frankel CA, Beckford A (1989): A review of phenotype-karyotype correlations in individuals with interstitial deletion of the long arm of chromosome 2. Am J Med Genet 32:359-363. Sanchez J, Pantano AM (1984): A case of deletion 2q35-qter and a peculiar phenotype. J Med Genet 21:147-149. Shabtai F, Klar D, Halbrecht I (1982): Patial deletion of chromosome 2. Delineable syndrome of deletion 2(q23-q31) Ann Genet 25: 156-158. Taysi K, Dengler DR, Jones LA, Heersma J R (1981):Interstitial deletion of the long arm of chromosome 2. Case report and review of literature. Ann Genet 24:245-247. Warter S, Lausecker C, Pennerath A (1976):Etudes chromosomique et clinique d’une fillette porteuse d’une deletion (2)(q34q36).Hum Genet 32:225-227. Winter RM, Baraitser M, Douglas JM (1984):A computerised database for the diagnosis of rare dysmorphic syndromes. J Med Genet 21:121-123. Young RS, Shapiro SD, Hansen K, Hine RK, Rainosek D, Guerra FA (1983): Deletion 2q: Two new cases with karyotypes 46,XY,de1(2) (q31q33) and 46,XX,de1(2)(q36).J Med Genet 20:199-202.
