Author: Dundar, M
Date published: April 1, 2011
Partial duplication of 3q is a rare chromosomal disorder that leads to multiple congenital abnormalities such as growth retardation, microcephaly and characteristic facial features such as hypertrichosis, synophrys, low frontal hairline, hypertelorism, upslanting palpebral fissures, low-set dysplastic ears, wide nasal bridge, anteverted nares, prominent maxilla, long philtrum, downturned corners of mouth, high arched palate, cleft palate, micrograthia (3). Less than 100 cases of the duplication 3q syndrome have been reported to date. Although the phenotype of the patient has similarities with Cornelia de Lange syndrome the etiology is different (3). Convulsions, ocular, renal and cardiac anomalies are more frequent in dup (3q) syndrome, while limb anomalies, hirsutism and synophrys are more characteristic of Cornelia de Lange syndrome (8).
The boy is the third child of healthy unrelated parents, who were 35 (mother) and 38 (father) years old at the time of delivery. Pregnancy was unremarkable. The boy was born two weeks after term by normal spontaneous vaginal delivery with normal birth weight and height. Occipito-frontal circumference (OFC) was 32 cm, below percentile 10. At age 9 months length (66cm) was at third centile, weight (7 kg) was below third centile and OFC (40 cm) was below third centile. Dysmorphic features include microcephaly, low frontal hair line, hemangioma at the forehead, hirsute forehead, prominent ears, synophrys, curved eyelashes, hypertelorism, wide and high nose bridge with anteverted nostrils, long philtrum, thin lips, high palate, micrognatia, low occipital hairline, widely spaced nipples, hypertrichosis, atypical simian line and bilateral cryptorchid testes. Ocular examination was normal. Cardiological examination revealed a 3/6 degree murmur and echocardiography revealed tetralogy of Fallot with pulmonary artery hypoplasia and pulmonary valve dysplasia. Pulmonary valvuloplastia was performed. Magnetic resonance imaging showed a sacrococcygeal teratoma confirmed by pathologic studies. Because of this sacrococcygeal teratoma he was operated and had a colostomy bag at the left low abdominal region (Fig. Ia, lb).
MATERIAL AND METHODS
A peripheral blood sample was cultured under stimulation with phytohemaglutinin by standard cytogenetic laboratory methods. Cytogenetic analysis of metaphase chromosomes was performed by GTG banding and also Ag-NOR staining and a small metacentric extra chromosome was present with only one chromosome 21.
His karyotype was designated as 46,XY,der(21)?t(?;21)(?;pl3) according to ISCN 2009. Parental karyotypes were also analyzed with GTG and were normal. FISH analysis was performed to determine the origin of the unknown part of derivative chromosome 21. Subtelomeric FISH was carried out with ToTefSfysion probes (\fysis Inc. Downer Grove, IL, USA) in accordance with the manufacturer's instructions. Hybridized metaphases were analyzed on an epifluorescence microscope (Zeiss Axiplan) equipped with a CCD camera (Photometries Sensys) and with MacProbe software v.4.1. program. FISH analysis indicated that the unknown part of the derivative chromosome 21 originated from chromosome 3 and his karyotype was redesignated as 46,XY,der(21)t(3;21)(q35;pl3) (Figs 2,3).
Partial trisomy of the long arm of chromosome 3 (dup3q) is a rare chromosomal abnormality that resembles Brachmann-de Lange syndrome which is also known as Cornelia de Lange Syndrome. Less than 100 cases of the duplication 3q syndrome have been reported to date. The first case of partial duplication 3q was described and the similarities with Cornelia de Lange Syndrome in 1966 by Falek et al. (3). Although the phenotypes of the cases have similarities with Cornelia de Lange Syndrome recently they were found to be etiologically different. The phenotypes of both syndromes overlap but convulsions, ocular, renal and cardiac anomalies are more frequent in dup(3q) syndrome, while limb anomalies, hirsutism and synophrys are more characteristic of Brachmann-de Lange syndrome (8). We present here a 9 month old boy with a de novo unbalanced translocation resulting in trisomy for distal 3q. Most cases with partial duplication of 3q are the result of malsegregation of a parental balanced translocation involving chromosome 3 (9). The most frequently duplicated segment spans from 3q21 to 3qter (13). So these patients were trisomie for a segment of 3q of variable length. Duplications involving segments distal to 3q27 are less common, and are less severely affected, usually with no major malformations or severe mental retardation (4, 14). A gene or genes at 3q26.31-q27.3 are most likely mandatory for the characteristic phenotype (5). This chromosomal abnormality is characterized by normal birth weight with postnatal growth retardation and presents characteristic dysmorphic features such as hypertrichosis, synophrys, low frontal hairline, microcephaly, hypertelorism, upslanting palpebral fissures, wide nasal bridge, anteverted nares, prominent maxilla, long philtrum, downturned corners of mouth, high arched palate, cleft palate, micrograthia, low-set dysplastic ears and short webbed neck. Fifth finger clinodactily, hypoplastic nails, simian crease, talipes equinovarus can also be present. Furthermore severe postnatal growth deficiency, severe mental deficiency, brain and ocular anomalies, seizures, congenital heart disease, renal and genitourinary malformations (especially cryptorchidism), omphalocele, and chest deformities were reported. Comparison with four cases with distal 3q duplications reported in the literature revealed typical common findings (Table I) (5, 11). Clinical features that are similar to our case include microcephaly, low frontal hair line, wide hemangioma at the forehead, forehead hirsutism, prominent ears, synophrys, curved eyelashes, hypertelorism, wide and high nasal bridge with anteverted nostrils, long philtrum, thin lips, high palate, absence of phrenulum at the tongue, micrognatia, low occipital hairline, wide spaced nipples, hypertrichosis, atypical simian line, bilateral cryptorchid testes, tetralogy of Fallot, pulmonary artery hypoplasia and pulmonary valve dysplasia. Besides these features sacrococcygeal teratoma is seen in the present patient.
Sacrococcygeal teratomas are common congenital teratomas showing an incidence of approximately 1:35,000^10,000 live births and a female-to-male ratio of approximately 4:1 (7). Although chromosomal aberrations have been found in teratomas, there is no publication with partial trisomy 3q. Mosaic trisomy of most of the long arm of chromosome 1, mosaic terminal 7q monosomy/distal 2p trisomy have been reported in patients with a sacrococygeal teratoma. Autosomal translocation between the chromosomes 1 and 15, balanced de novo translocation between the chromosomes 2 and 7, unbalanced translocation between the chromosomes 10 and 17 that resulted from a maternal balanced autosomal translocation were also reported (1, 2, 6, 10, 12). The role of chromosomal abnormalities in the pathogenesis of teratomas has not been fully elucidated but these findings suggest that amplification of certain genetic loci might be responsible (2, 10).
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BY M. DUNDAR1, A. UZAK 1, M. ERDOGAN1, C. SAATCI1, S. AKDENIZ2, G. LULECI2, I. KESER2 AND S. KARAUZUM2
(1) Erciyes University, Medical Faculty, Department of Medical Genetics, Kayseri, Turkey.
(2) Akdeniz University, Medical Faculty, Department of Medical Biology and Genetics, Antalya, Turkey.
ADDRESS FOR CORRESPONDENCE:
Dr. Munis Dundar, MD., PhD.
Erciyes University, Medical Faculty,
Department of Medical Genetics
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