American Journal of Medical Genetics 43:1039-1040 (1992)
Letter to the Editor ~
~~
Ring Chromosome 7, Hyperpigmented Skin Lesions and Malignant Melanoma To the Editor: A recent issue of the Journal included a report of a child with a ring chromosome 7 who presented the most severe abnormalities of any r(7) individual thus far reported [Biesecker et al., 19911. This article brings to nine the number of individuals reported with a ring chromosome 7 [Biesecker et al., 1991; Caramia et al., 1990; de Barros et al., 1986; DeLozier et al., 1982; Kohyama et al., 1988; Koiffmann et al., 1990; Nakano and Miyamoto, 1977; Zackai and Breg, 19731. In no case was a deletion of chromosome 7 demonstrable by cytogenetic techniques, and although the phenotype of these individuals varies widely, no obvious correlation can be drawn between the phenotypic severity and the presence of mosaicism (in 319 cases the ring formation was probably postzygotic) or of ring instability as assessed by cytogenetic studies of lymphocytes and fibroblasts. The phenotype has included mental retardation in the majority of cases, but major malformations are apparently rare. Only 2 manifestations were present in all patients reported: short stature, and hyperpigmented skin lesions, most often multiple, congenital, large melanocytic naevi andlor caf6-au-lait spots. These patients are probably at increased risk for the development of skin malignancies because of such dermatologic lesions. The girl we reported in DeLozier et al. [19821 developed a malignant melanoma a t age 18 years. minor At age 8 years she had short stature ( - 2 S.D.), skeletal anomalies, and normal intelligence. The only striking findings were dermatological: cutis marmorata, naevi flammei of the forehead, vertex, and nape of the neck, and multiple pigmented naevi on all parts of the body, varying in size (0.3-1.0 cm for most, but up to 5.5 x 3.0 cm) and shape (flat or raised). The 3 largest lesions, hyperpigmented and verrucous, were located on the right knee and thigh and the left calf. After they were removed for prophylactic reasons, histology confirmed these as congenital compound naevi. Although it was highly recommended that she be followedregularly by a dermatologist, this was not done. At age 18 years she consulted a dermatologist because of Received for publication June 21, 1991; revision received September 25, 1991. Address reprint requests to Dr. C.D. DeLozier-Blanchet,University Institute of Medical Genetics, CMU, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
0 1992 Wiley-Liss, Inc.
chronic itching of a melanocytic naevus behind the right ear, which was probably congenital but had changed in appearance over the previous several months. After removal, histology showed a malignant melanoma of an unclassified type, Clark level IV, Breslow 1.8 mm. When the patient was referred to the University Hospital for a wide surgical excision, several small pigmented papules were observed around the scar. Histologic examination confirmed the diagnosis of “satellite” metastases of the malignant melanoma. At that time no evidence of distant metastases was found on clinical examination or by CT scan of the cervical and thoraco-abdominal regions or of the central nervous system. Eye fundi, standard X-rays of skeleton, and blood chemistry were all normal. No further treatment was recommended, but the patient has bimonthly clinical examinations. Two years later she has no clinical or radiological signs of recurrence. Generally speaking, the patient’s evolution has been normal in most respects in spite of her chromosome abnormality. Her general health has been good, with a minor tendency to atopic disease (hay fever, slight asthma) which is not known in other family members. At age 19 years she is still short: 147 cm for a weight of 44 kg and occipito-frontal circumference of 53.8 cm (her mother measures 160 cm, father 172 cm, and normal younger sister 167 cm). Her intellectual development has been normal; she completed high school and is now considering nursing studies. Menses began at age 13 years, with generally irregular cycles and periods of amenorrhea lasting several months. Secondary sexual characteristics are present but somewhat underdeveloped, and she appears several years younger than her age. Physical examination was remarkable only for the dermatological anomalies: livedo of the thighs, flat angioma of the forehead, scalp, and back of the neck, and multiple melanocytic naevi on the trunk, face, and limbs. We thus confirm the constant association of ring chromosome 7 with hyperpigmented skin lesions, which may be subject to malignant degeneration. It is hoped that molecular analyses will allow identification of the genes deleted from the terminal portions of chromosome 7, since the alteration of one or several of them might be related to the melanocytic lesions and their potential malignant evolution.
ACKNOWLEDGMENTS The authors would like t o thank Dr. J. Lilla for referring the patient and Professors J.-H. Saurat and E. En-
1040
DeLozier-Blanchetet al.
gel for their clinical guidance and advice concerning this letter.
REFERENCES Biesecker LG, Cox B, Glover TW (1991):Severe anomalies associated with ring chromosome 7. Am J Med Genet 40:429-431. Caramia GM, Baroncini A, Osimani R, Forabosco A (1990): Ring chromosome 7: Report of the fifth case. Eur J Pediatr 149:475-476. de Barros LP, Alvarez Perez AB, Brunoni D, Andrade JAD (1986): Cromossoma 7 em anel-relato de um caso. Cienc Cult 38 (Suppl):849. DeLozier CD, Theintz G, Sizonenko P, Engel E (1982):A fourth case of ring chromosome 7. Clin Genet 22:90-98. Kohyama J, Watanabe S, Nakajima M, Suzumura H, Ishikawa T, Ishikawa K, Saito F, Fukuda C (1988): Ring chromosome 7: Report of a case. Acta Paediatr Jpn 30:517-519. Koiffmann CP, Diament A, de Souza DH, Wajntal A (1990): Ring chromosome 7 in a man with multiple congenital anomalies and mental retardation. J Med Genet 27:462-464.
Nakano S, Miyamoto N (1977): A ring C7 chromosome in a mentally and physically retarded male with various somatic abnormalities. Jpn J Hum Genet 22:33-41. Zackai EH, Breg WR (1973): Ring chromosome 7 with variable phenotypic expression. Cytogenet Cell Genet 12:40-48.
C.D.DeLozier-Blanchet University Institute of Medical Genetics Geneva, Switzerland I. Masouye S. Vollenweider Dermatology Clinic Geneva Cantonal Hospital Geneva, Switzerland
Letter to the Editor ~
~~
Ring Chromosome 7, Hyperpigmented Skin Lesions and Malignant Melanoma To the Editor: A recent issue of the Journal included a report of a child with a ring chromosome 7 who presented the most severe abnormalities of any r(7) individual thus far reported [Biesecker et al., 19911. This article brings to nine the number of individuals reported with a ring chromosome 7 [Biesecker et al., 1991; Caramia et al., 1990; de Barros et al., 1986; DeLozier et al., 1982; Kohyama et al., 1988; Koiffmann et al., 1990; Nakano and Miyamoto, 1977; Zackai and Breg, 19731. In no case was a deletion of chromosome 7 demonstrable by cytogenetic techniques, and although the phenotype of these individuals varies widely, no obvious correlation can be drawn between the phenotypic severity and the presence of mosaicism (in 319 cases the ring formation was probably postzygotic) or of ring instability as assessed by cytogenetic studies of lymphocytes and fibroblasts. The phenotype has included mental retardation in the majority of cases, but major malformations are apparently rare. Only 2 manifestations were present in all patients reported: short stature, and hyperpigmented skin lesions, most often multiple, congenital, large melanocytic naevi andlor caf6-au-lait spots. These patients are probably at increased risk for the development of skin malignancies because of such dermatologic lesions. The girl we reported in DeLozier et al. [19821 developed a malignant melanoma a t age 18 years. minor At age 8 years she had short stature ( - 2 S.D.), skeletal anomalies, and normal intelligence. The only striking findings were dermatological: cutis marmorata, naevi flammei of the forehead, vertex, and nape of the neck, and multiple pigmented naevi on all parts of the body, varying in size (0.3-1.0 cm for most, but up to 5.5 x 3.0 cm) and shape (flat or raised). The 3 largest lesions, hyperpigmented and verrucous, were located on the right knee and thigh and the left calf. After they were removed for prophylactic reasons, histology confirmed these as congenital compound naevi. Although it was highly recommended that she be followedregularly by a dermatologist, this was not done. At age 18 years she consulted a dermatologist because of Received for publication June 21, 1991; revision received September 25, 1991. Address reprint requests to Dr. C.D. DeLozier-Blanchet,University Institute of Medical Genetics, CMU, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
0 1992 Wiley-Liss, Inc.
chronic itching of a melanocytic naevus behind the right ear, which was probably congenital but had changed in appearance over the previous several months. After removal, histology showed a malignant melanoma of an unclassified type, Clark level IV, Breslow 1.8 mm. When the patient was referred to the University Hospital for a wide surgical excision, several small pigmented papules were observed around the scar. Histologic examination confirmed the diagnosis of “satellite” metastases of the malignant melanoma. At that time no evidence of distant metastases was found on clinical examination or by CT scan of the cervical and thoraco-abdominal regions or of the central nervous system. Eye fundi, standard X-rays of skeleton, and blood chemistry were all normal. No further treatment was recommended, but the patient has bimonthly clinical examinations. Two years later she has no clinical or radiological signs of recurrence. Generally speaking, the patient’s evolution has been normal in most respects in spite of her chromosome abnormality. Her general health has been good, with a minor tendency to atopic disease (hay fever, slight asthma) which is not known in other family members. At age 19 years she is still short: 147 cm for a weight of 44 kg and occipito-frontal circumference of 53.8 cm (her mother measures 160 cm, father 172 cm, and normal younger sister 167 cm). Her intellectual development has been normal; she completed high school and is now considering nursing studies. Menses began at age 13 years, with generally irregular cycles and periods of amenorrhea lasting several months. Secondary sexual characteristics are present but somewhat underdeveloped, and she appears several years younger than her age. Physical examination was remarkable only for the dermatological anomalies: livedo of the thighs, flat angioma of the forehead, scalp, and back of the neck, and multiple melanocytic naevi on the trunk, face, and limbs. We thus confirm the constant association of ring chromosome 7 with hyperpigmented skin lesions, which may be subject to malignant degeneration. It is hoped that molecular analyses will allow identification of the genes deleted from the terminal portions of chromosome 7, since the alteration of one or several of them might be related to the melanocytic lesions and their potential malignant evolution.
ACKNOWLEDGMENTS The authors would like t o thank Dr. J. Lilla for referring the patient and Professors J.-H. Saurat and E. En-
1040
DeLozier-Blanchetet al.
gel for their clinical guidance and advice concerning this letter.
REFERENCES Biesecker LG, Cox B, Glover TW (1991):Severe anomalies associated with ring chromosome 7. Am J Med Genet 40:429-431. Caramia GM, Baroncini A, Osimani R, Forabosco A (1990): Ring chromosome 7: Report of the fifth case. Eur J Pediatr 149:475-476. de Barros LP, Alvarez Perez AB, Brunoni D, Andrade JAD (1986): Cromossoma 7 em anel-relato de um caso. Cienc Cult 38 (Suppl):849. DeLozier CD, Theintz G, Sizonenko P, Engel E (1982):A fourth case of ring chromosome 7. Clin Genet 22:90-98. Kohyama J, Watanabe S, Nakajima M, Suzumura H, Ishikawa T, Ishikawa K, Saito F, Fukuda C (1988): Ring chromosome 7: Report of a case. Acta Paediatr Jpn 30:517-519. Koiffmann CP, Diament A, de Souza DH, Wajntal A (1990): Ring chromosome 7 in a man with multiple congenital anomalies and mental retardation. J Med Genet 27:462-464.
Nakano S, Miyamoto N (1977): A ring C7 chromosome in a mentally and physically retarded male with various somatic abnormalities. Jpn J Hum Genet 22:33-41. Zackai EH, Breg WR (1973): Ring chromosome 7 with variable phenotypic expression. Cytogenet Cell Genet 12:40-48.
C.D.DeLozier-Blanchet University Institute of Medical Genetics Geneva, Switzerland I. Masouye S. Vollenweider Dermatology Clinic Geneva Cantonal Hospital Geneva, Switzerland
