A Girl with 15q Overgrowth Syndrome and dup(15)(q24q26.3) that Included Telomeric Sequences

María de los Ángeles Gutiérrez-Franco; María de la Luz Madariaga-Campos; Ana I. Vásquez-Velásquez; Esmeralda Matute; Guevara-Yáñez Roberto; Horacio Rivera

doi:10.3343/kjlm.2010.30.3.318

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Gutiérrez-Franco, Madariaga-Campos, Vásquez-Velásquez, Matute, Roberto, and Rivera: A Girl with 15q Overgrowth Syndrome and dup(15)(q24q26.3) that Included Telomeric Sequences

Case Report

Korean J Leg Med 2010;30(3):318-324.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.3.318

A Girl with 15q Overgrowth Syndrome and dup(15)(q24q26.3) that Included Telomeric Sequences

María de los Ángeles Gutiérrez-Franco, M.D.¹, María de la Luz Madariaga-Campos, M.S.¹, Ana I. Vásquez-Velásquez, M.S.², Esmeralda Matute, Ph.D.³, Guevara-Yáñez Roberto, M.S.⁴, Horacio Rivera, M.D.^2,⁵

¹Department of Genetics, Institute of Biological Sciences, Autonomous University of Guadalajara, Mexico

²Division of Genetics, CIBO, Mexican Institute of Social Welfare, Mexico

³Institute of Neurosciences, CUCBA, University of Guadalajara, Mexico

⁴BIOGEN Laboratory, Guadalajara, Mexico

⁵Human Genetics Doctorate Program, CUCS, University of Guadalajara, Guadalajara, Mexico

Corresponding author: Horacio Rivera, M.D. División de Genética, CIBO, Instituto Méxicano del Seguro Social, Sierra Mojada 800, C.P: 44340, Guadalajara, México Tel: +52-33-36189410, Fax: +52-33-36181756 E-mail: hrivera@cencar.udg.mx

Revised 4 December 20095 February 2010 Accepted 25 February 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Distal 15q trisomy or tetrasomy is associated with a characteristic phenotype that includes mild to moderate intellectual disability, abnormal behavior, speech impairment, overgrowth, hyperlaxity, long face, prominent nose, puffy cheeks, pointed chin, small ears, and hand anomalies (mainly arachno- and camptodactyly). We present the case of a 13-yr-old girl with the main clinical features of 15q overgrowth syndrome and a 46,XX,dup(15)(q24q26.3)[117]/46,XX[3].ish dup(15)(q24q26.3) (SNPRN+,PML+,subtel++,tel++) de novo karyotype. The findings in this case are consistent with those in the previous distal 15q trisomy cases that presented with overgrowth and mental retardation. Further, the rearranged chromosome had a double set of directly oriented telomeric and sub-telomeric sequences.

Keywords: Chromosome 15, Distal 15q duplication, 15q overgrowth syndrome, Interstitial telomere

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Fig. 1.

Images of the patient as a newborn (A and B) and at 13 yr of age (C and D). (A) Note the sloping forehead, palpebral fissures oriented slightly downwards and outwards, bulbous nose with prominent bridge and septum, puffy cheeks, midline crease in the lower lip, and micrognathia. (B) Additional postaxial rudimentary digits and overlapping fingers in both hands. (C) Note the high forehead, elongated face, large nose, and pointed prominent chin. (D) Arachno-camptodactyly in both hands.

Fig. 2.

The patient's dup(15)(q24q26.3). (A) 3 G-banded chromosome 15 pairs with the duplicated homolog on the right. Note the distinct satellites on the normal member. (B) A partial metaphase after FISH with the dual-color Prader-Willi/Angelman (SNRPN) Region and 15q subtel clone 154P1 probe set labeled red and green, respectively; note the double 15q subtel green signal directly oriented. (C) A partial metaphase after FISH with the pantelomeric probe (red signal); note 2 signals in the same direct orientation.

Table 1.

Cytogenetic and clinical findings in 16 patients with a “pure” distal 15q duplication∗

	Coco and Penchaszadeh [9]	Yip et al. [11]	Chandler et al. [12]	Abe et al. [13]	Okubo et al. [14]	Faivre et al. [15]	Roggenbuck et al. [16]			Bonati et al. [17]	Kant et al. [18]	Tatton-Brown et al. [6]				Present case	Distal 15q duplication [2-6]
											Kant et al. [18]	Family A		Family B
							Case 1 Twin 1	Case 2 Twin 2	Case 3		Case A	Case II-3	Case III-2	Case II-2	Case II-6
Sex/Age	M/20 mo	M/9 mo	F/13 yr 4 mo	F/9 mo	M/5 yr	M/22-wk fetus	F/1 d^†	F/4 yr 6 mo	M/21 mo	M/4 yr 8 mo	F/3 yr 4 mo	F/adult	M/18 mo	F/38 yr	M/33 yr	F/13 yr 10 mo
Duplicated segment	15q22→qter	15q21→qter	15q24→qter	15q24.3→q26.3	15q25→qter	15q25→qter	15q24→q26.3	15q24→q26.3	15q24→q26.3	15q25.2→qter	15q26.1→qter	15q26.1→qter	15q26.1→qter	15q26→qter	15q26→qter	15q24→qter	15q2→qter
Rearrangement and occurrence	inv(15) (p1q22) mat	dir dup dn mosaic 46,XY	dir dup dn	dir dup dn	inv(15) (p11.2q25) mat	add (15) (p11)dn mosaic 46,XY	dir dup dn	dir dup dn	dir dup dn	add(15) (p11)dn	t(15;21) (26.1;p12) uk	inv(15) (p12q26.1) pat	inv(15) (p12q26.1) pat	t(14;15) (p11.2;q26) mat	t(14;15) (p11.2;q26) mat	dir dup dn mosaic 46,XX	Diverse
Mental or psychomotor retardation	+	+	+	+	+	NA	NA	+	+	+	+	NR	+	NR	NR	+	+
Defective speech		NA	+	NA	+	NA	NA	+	+	+	+	NR	+	+	+	+	+
Height		<3 percentile	NL	<3 percentile	>97 percentile	>97 percentile	NR	<3 percentile	NL	>97 percentile	97 percentile	>97 percentile	>97 percentile	>97 percentile	>97 percentile	>97 percentile	>97 percentile
OFC		NL	<3 percentile	NL	>97 percentile	NL	Anencephaly	<3 percentile	<3 percentile	<3 percentile	97 percentile	NR	>97 percentile	NL	NL	NL	>97 percentile
Long distinctive face	+	-	+	-	+	NR	NR	+	-	-	+	+	Mildly dysmorphic	+	+	+	+
Prominent or bulbous nose	-	+	-	-	-	NR	NR	-	+	-	+	+	-	+	+	+	+
Pointed or prominent chin		-	-	-	+	NR	NR	-	-	-	-	+	+	+	+	+	+
Puffy cheeks	NR	+	-	+	+	-	NA	+	-	NR	-	+	-	+	+	+	+
Congenital heart disease	-	Hypertrophic ventricular septum	Patent ductus arteriosus	Patent ductus arteriosus	NR	NR	NR	-	VSD and ASD		NR	NR	-	-	-	-	+
Renal anomalies	NR	-	Horseshoe	-	-	NR	NR	-	-	-	NR	Horseshoe	Right agenesis	-	-	-	+
Abnormal fingers	Short, stubby	Brachydactyly	Arachnodactyly	Syndactyly	NR	NR	NR	Syndactyly, long tapered fingers and incurved toes	Clinodactyly	NR	NR	NR	Tapered fingers, overlapping toes	Clinodactyly, overlapping toes	NR	Poly, arachno, and camptodactyly	+

The fetus reported in ref. [10] was not included because of the lack of a detailed description;

^† dead.

Abbreviations: mat, maternal; dn, de novo; uk, unknown; pat, paternal; NA, not applied; NR, not reported; NL, normal; OFC, occipitofrontal circumference.

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