BOY WITH SEIZURES (WEST SYNDROME) AND DISTAL 7q DUPLICATION SYNDROME DUE TO AN UNBALANCED 7q;9p TRANSLOCATION

Summary: Boy with seizures (West syndrome) and distal 7q duplication syndrome due to an unbalanced 7q;9p translocation: We report a 15 month old boy with prominent metopic suture, epicanthal folds, strabismus, low-set ears, microretrognathia, large anterior fontanel, bilateral simian creases, muscular hypotonia, and severe psychomotor retardation. He also had West syndrome. An electroencephalogram showed hypsarrythmia, and cranial MR indicated a myelinisation delay. Standard karyotyping showed additional material on one chromosome 9p. Using FISH, a terminal 7q duplication spanning 26 Mb in size and a terminal 9p deletion sized (at least) 9.1 Mb were identified. The father had a karyotype of t(7;9)(q33;p23) and the mother's karyotype was normal. The boy presented typical facial features of the distal 7q duplication syndrome but no genital anomalies attributable to his distal 9p deletion. We assume that the severe epilepsy is likely due to the trisomy 7q. Key-words: West syndrome - Trisomy 7q33[arrow right]qter - Monosomy 9pter[arrow right]p23 INTRODUCTION Duplication of the distal long arm of chromosome 7 is associated with multiple abnormalities and developmental delay. Approximately 50 patients with distal trisomy 7q and unbalanced translocations have been reported to date (1, 3, 5, 6, 9, 11), including a girl with distal trisomy 7q and distal monosomy 9p (9), a combination also occurring in the boy presented here. Novales et al. (7) grossly classified the partial duplications of chromosome 7q by phenotype and chromosomal location; the duplications of 7q22[arrow right]q31, 7q31[arrow right]qter, and 7q32[arrow right]qter were found to display characteristic clinical features. In their report of five patients with 7q duplication and review of 36 previous patients, Forabosco et al. (3) proposed that the prognosis mainly relates to the size of the duplicated segment: duplications distal of 7q32 did not recognizably reduce life expectancy but larger duplications frequently conferred early mortality. The phenotype varies with the size of the duplicated segment. A distal 7q duplication syndrome characterised by high forehead, frontal bossing, low-set ears, downslanting palpebral fissures, strabismus, cleft palate, hydrocephalus, muscle hypotonia, and developmental delay) has been tentatively identified (1,3,6). Larger duplications (7q21[arrow right]qter) have been associated with additional craniofacial and malformations of internal organs and severe mental retardation (2, 3, 7, 12). We present a boy with facial abnormalities suggestive of the distal trisomy 7q syndrome, infantile spasms (West syndrome), severe developmental delay, trisomy 7q33[arrow right]qter, and monosomy 9pter[arrow right]p23. CASE REPORT A 15 month old Turkish boy (Fig. 1a) was referred because of facial anomalies and developmental delay. After an uneventful pregnancy, he had been born at term by spontaneous delivery to a 32 year old mother and a nonconsanguineous 28 year old father. Birth weight was 3,000 g (-0.7 SD), length 49 cm (-0.1 SD), and occipitofrontal circumference (OFC) 34 cm (+0.2 SD). He had tonic seizures on days 15 and 40 and an electroencephalogram (EEG) indicating hypsarrythmia (Fig. 1c). At the age of 15 months, weight was 9,000 g (-2 SD), length 75 cm (-0.8 SD), and OFC 47 cm (-1 SD). He had large anterior fontanel, prominent metopic suture, hypotelorism, telecanthus, epicanthal folds, strabismus, low-set ears, downcurved upper lip, and microretrognathia (Fig. 1a). He also had bilateral simian creases, and camptodactyly of the 4th and 5th fingers. His first toes were long and broad (Fig. 1b). The right testis was in the inguinal canal and the left testicle was not palpable. He had muscular hypotonia and head control for short periods of time. He used no meaningful words. Cranial magnetic resonance imaging revealed delayed myelinisation. Skeletal X-rays, abdominal ultrasonography, and an echocardiogram were normal. …