Pediatrics and (2011) 52, 287e289

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CASE REPORT Siblings With 22q13.3 and 15q26 Inherited From a Maternally Balanced Translocation

Pen-Hua Su a,b, Jia-Yuh Chen a,b,*, Suh-Jen Chen a a Department of , Chung Shan Medical University Hospital, Taichung, Taiwan b Department of Pediatrics, School of , Chung Shan Medical University, Taichung, Taiwan

Received Feb 24, 2010; received in revised form Aug 24, 2010; accepted Sep 28, 2010

Key Words We describe two siblings with generalized , expressive language delay, develop- accelerated growth; mental delay, mild facial dysmorphism, and accelerated growth. In addition, the male sibling deletion 22q; had testis dysgenesis. Cytogenetic evaluation revealed an unbalanced maternally inherited duplication 15q translocation t(15;22)(q26;q13.3) resulting in partial 22q and trisomy 15q. The combination of deletion 22q and duplication 15q has not been described previously. Copyright ª 2011, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.

1. Introduction seven cases with cytogenetically visible and two cryptic terminal deletions of 22q13.3 have been described. These is associated with several clinically rele- patients demonstrated a generalized developmental vant cytogenetic anomalies. Cat-eye syndrome is usually delay, abnormal or accelerated growth, hypotonia, severe e delays in expressive speech, and mildly dysmorphic facial associated with a chromosome 22 derived bisatellited 4,5 supernumerary chromosome.1 DiGeorge syndrome or features. velocardiofacial syndrome is associated with a deletion or To date, only one case of trisomy 15q26.1 has been microdeletion of chromosome 22q11.2,3 Although chromo- described in the literature. The 35-year-old and profoundly some abnormalities involving band 22q11 have been well mentally retarded male demonstrated multiple dysmorphic studied, little is known about chromosome abnormalities stigmata, including large dysplastic ears, short neck, of 22q13, the most distal band. In the literature, only mandibular prognathism, large bulbous deviated nose, large thick lips, severe kyphoscoliosis, pectus excaratum, horseshoe kidney, and crytorchidism.6 Here, we describe two siblings with an unbalanced * Corresponding author. Department of Pediatrics, Chung Shan maternally inherited translocation t(15;22)(q26.1;q13.3) Medical University Hospital, No. 110, Section 1, Chien-Kuo North Road, Taichung City 402, Taiwan. resulting in partial monosomy 22q and partial trisomy 15q. E-mail address: [email protected] (J.-Y. Chen). This translocation has not been previously described, and

1875-9572/$36 Copyright ª 2011, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved. doi:10.1016/j.pedneo.2011.06.008 288 P.-H. Su et al some obvious differences in growth rate between the genders in these cases were observed.

2. Case Report

Case 1 (Proband 1) presented at 30 days of age for evalu- ation of hypotonia. He had a birth weight of 2750 g (10th percentile); birth length of 51 cm (50th percentile); head circumference (HC) of 34 cm (10the25th percentile); and was born after 36 weeks of gestation to a 30-year-old gravida 2, para 2 woman. His Apgar scores were 9 at 1 minute and 10 at 5 minutes. During the newborn period, he Figure 1 and ideogram of G-banding showing was noted to have a down-slanting palpebral fissure, (A) Mother; balanced translation t(15;22)(q26.1q13.3) and bulbous nasal bridge, long philtrum, retro- and micro- (B) proband; the der(22)t(15;22)(q26.1;q13.3)mat. gnathia, crumpled ears, a persistent foramen ovale, and feeding difficulties. The patient received hernioplasty because of an incarcerated inguinal hernia and testis 3. Discussion dysgenesis. He presented with sensorineural hearing loss and developmental delay, and was rolling at 13 months, Although abnormal rearrangement of proximal chromosome sitting at 15 months, crawling at 21 months, pulled to 15q is commonly seen in cases of inv dup(15), trisomy of the a stand at 24 months, and walked alone at 30 months. On distal region of chromosome 15q is rare. Duplication 15q physical examination at 30 months of age, his length was syndrome was initially described by Fujimoto et al.7 Dupli- th th th 92 cm (25 e50 percentile), weight was 14 kg (50 cation of distal 15q has now been described in at least 28 th percentile), and HC was 52 cm (>97 percentile). A brain additional cases.8 The breakpoints are all mapped between magnetic resonance imaging showed a mild delay in mye- bands 15q21 and 15q23, except for two families with lination and a thin appearance of the corpus callosum. Bone breakpoints at 15q25 and two families with breakpoints at age was mildly advanced to 3 years at 2 years and 7 months 15q15. The clinical phenotype includes postnatal growth of age. The body height of this patient’s father was 160 cm deficiency and severe to profound mental retardation. and that of his mother was 158 cm. However, two patients with duplication of 15q25/qter Case 2 (Proband 2) is the elder sister of Case 1 and presented with only mild retardation. Most of the duplication presented at 2 years and 9 months of age for evaluation 15q cases result from unbalanced translocations, all but one of developmental delay. She was born weighing 3250 g of which were the offsprings of a balanced carrier parent. th th (25 e50 percentile) after a 39-week gestation after Despite the fact that the second chromosome involved in the cesarean delivery because of meconium stain. Fetal move- reciprocal translocation has varied, the clinical phenotype is ments were not noted during pregnancy. In the newborn consistent. A summary and comparison of the anomalies of period, the patient was noted to have congenital pneumonia, patients with isolated trisomy 15q and monosomy 22q, as feeding difficulties, and hypotonia. She presented with well as our sibling cases, are listed in Table 1. developmental delay and was rolling at 8 months, sitting at 9 months, crawling at 11 months, pulled to stand at 20 months, walked alone at 27 months, and babbled but did not produce any words until 42 months. On physical exami- Table 1 Summary of findings. nation at 2 years and 9 months of age, her length was 95 cm Study Trisomy Case 1 Case 2 Deletion (75the90th percentile), weight was 18 kg (>97th percentile), 15q26 22q13.3 and HC was 51 cm (>97th percentile). She had a down- Down-slanting palpebral þ þþ slanting palpebral fissure, bulbous nose, broad nasal fissure bridge, long philtrum, and micrognathia. Brain magnetic Bulbous nose þþ resonance imaging showed delayed myelination, a thin Broad nasal bridge þ þþ appearance of the corpus callosum, hydrocephalus, and Long philtrum þ þþ cerebellum atrophy. The bone age was advanced to 5 years at High-arch palate þ 3 years and 9 months of age. Micrognathia þ þ Heart defects þ 2.1. Cytogenetic analysis Developmental delay/ þ þþþ mental retardation Cytogenetic analysis was performed on Probands 1 and 2 as Joint defects þ well as their parents. The results of Giemsa-trypsin banding Sensorineural hearing loss þ showed a derivative chromosome 22 suggestive of an Slender fingers and toes þ þ unbalanced translocation (Figure 1B). The paternal chro- Hypotonia þ þþþ mosomes were normal (46, XY). A balanced translocation þþþ between the long arm of and the long arm þ Z condition present; Z condition not present; Z condition of chromosome 22 in the mother was detected (Figure 1A). present or absent. The breakpoints were at 15q26.1 and 22q13.3. Siblings with deletion 22q13.3 and trisomy 15q26 289

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