172 Short case report
An infant with trisomy 15 mosaicism Sedat Isıkay and Kursat B. Carman Clinical Dysmorphology 2013, 22:172–174 Department of Pediatric Neurology, Gaziantep Children’s Hospital, Gaziantep, Turkey
Correspondence to Kursat B. Carman, MD, Gaziantep Children’s Hospital, Gaziantep 27000, Turkey Tel: + 90 342 360 0888; fax: + 90 342 360 0890; e-mail: [email protected] Received 25 January 2013 Accepted 8 August 2013
List of key features Trisomy 15 mosaicism Minor facial abnormalities Anterior anus
Introduction Conceptions with autosomal trisomies are usually aborted spontaneously in the first trimester of pregnancy. Trisomy 15 accounts for 7.6% of all trisomic abortions and 1.68% of all first-trimester pregnancy losses (Prontera et al., 2006). Few cases of mosaic trisomy 15 in liveborn infants have been reported (Codwell et al., 1981; Stallard and Sommer, 1989; Kuller and Laifer, 1991; Lahdetie and Lakkala, 1992; Fryns et al., 1993; Bu ¨hler et al., 1996; Milunsky et al., 1996; Zaslav et al., 1998; Olander et al., 2000; Prontera
et al., 2006). We report here the clinical features of an infant with mosaicism for trisomy 15.
Case report A 2-month-old girl was admitted to the paediatric neurology unit because she had marked hypotonia. She was born by Caesarean section at 38 weeks of gestation after a normal pregnancy and was the first child born to first-cousin parents; the mother was aged 32 years at her birth. Physical and neurological examination revealed a head circumference of 37 cm (25th–50th percentiles), height of 54 cm (10th–25th percentiles), and weight of 4.5 kg (25th–50th percentiles). Her muscle tone was hypotonic and deep tendon reflexes were hypoactive. Talipes equinovarus was noticed on both feet. The patient had trigonocephaly with a prominent forehead,
Fig. 2 Fig. 1
Dysmorphic facial features of infant. c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins 0962-8827
Discrete depression on the posterior surface of the helical rim of ear.
DOI: 10.1097/MCD.0000000000000012
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
An infant with trisomy 15 mosaicism Isıkay and Carman 173
small palpebral fissures, wide epicanthic folds, a broad flat nasal bridge, a small mouth, a high arched palate, and micrognathia (Fig. 1). The ears were low-set and there Fig. 3
were several discrete depressions on the posterior surfaces of the helical rim of both ears (Fig. 2). A transverse palmar crease was present on her right hand. She had anterior placement of her anus (Fig. 3). Laboratory investigations including complete blood count, biochemical studies, and thyroid function tests yielded normal results. Brain MRI, echocardiography, and abdominal ultrasonography also produced normal findings. Cytogenetic analysis of her peripheral blood revealed a mosaic 46,XX/47,XX, + 15 karyotype (Fig. 4). After the initial analysis, we increased the metaphase count up to 100, which showed the abnormal karyotype to be present in 30 of 100 cells.
Discussion We report a liveborn patient with trisomy 15 mosaicism. She presented with hypotonia and dysmorphic features. Trisomy 15 mosaicism is rarely reported and there have been only nine documented liveborn cases (Codwell et al., 1981; Stallard and Sommer, 1989; Kuller and Laifer, 1991; Lahdetie and Lakkala, 1992; Fryns et al., 1993; Bu ¨hler
Anterior placement of anus.
Fig. 4
1
2
3
6
7
8
13
14
15
19
20
4
9
21
5
10
11
12
16
17
18
22
X
Y
Cytogenetic analysis indicating trismony 15.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
174 Clinical Dysmorphology 2013, Vol 22 No 4
Table 1
Clinical and radiologic some features of patients with trisomy 15 mosaicism Codwell Stallard and Kuller and Lahdetie and Fryns et al. Bu¨hler et al. Milunsky Olander Prontera et al. (1981) Sommer (1989) Laifer (1991) Lakkala (1992) (1993) (1996) et al. (1996) et al. (2000) et al. (2006)
Sex Female Newborn Age at examination Developmental + delay Broad nasal + bridge Upturned nose – Large + prominent nose Small mouth + Micrognathia/ + retrognathia Abnormal ears + Abnormal ribs + Talipes + equinovarus Anteriorly + placed anus Congenital + heart disease
Male 6 months
Male Newborn
Female Newborn
Female 3 months
Male 1 month
Female Newborn
Male Newborn
Female 4 years
This study Female 1 month
+
+
+
+
–
+
+
+
+
+
+
–
+
+
+
+
+
+
+ –
– +
– –
+ +
+ +
+ +
– –
– –
+ +
– –
+ –
– –
+ +
+ +
+ +
– +
+ +
+ +
– NA –
– – –
– – –
– – –
– + +
+ + –
+ – –
– + –
+ – +
–
–
–
+
–
+
–
–
+
–
–
+
+
–
+
+
–
–
NA, not available.
et al., 1996; Milunsky et al., 1996; Olander et al., 2000; Prontera et al., 2006). The most consistent clinical characteristics of trisomy 15 mosaics are minor facial anomalies and congenital heart disease. Ventricular septal defect, patent foramen ovale, and patent ductus arteriosus have all been reported (Zaslav et al., 1998). However, the echocardiographic investigation of our patient revealed normal findings. Some clinical and radiological features of previous cases are listed in Table 1. Trisomy 15 is usually associated with advanced maternal age. In previous cases, when the parent of origin was studied, most cases occurred as a result of nondisjunction in maternal meiosis I (Zaragoza et al., 1994). In the present case, the mother was 32 years old. Unfortunately, we were not able to show the origin of trisomy in our patient. The origin of the mosaicism may have been due to a trisomic conception undergoing subsequent ‘trisomy rescue’ resulting in a trisomic and apparently normal cell line. Some of these occurrences are associated with uniparental disomy in the apparently normal cell line, which may give rise to features of Prader–Willi or Angelman syndrome depending on parental origin. Apart from hypotonia there were no convincing features of these disorders in our patient. Alternatively, the mosaicism may have resulted from a mitotic error. We were not able to test our patient further to explore the origins of the mosaicism, although we think the most likely origin is either a mitotic error in an originally normal conception or trisomy rescue, resulting in a trisomic cell line and a normal cell line with both a paternal and maternal chromosome 15, as the child had abnormalities in keeping with previously reported cases (Zaslav et al., 1998).
In conclusion, we report a case with trisomy 15 mosaicism. It should be considered in the differential diagnosis of patients presenting with hypotonia and dysmorphic features.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References Bu¨hler EM, Bienz G, Straumann E, Bo¨sch N (1996). Delineation of a clinical syndrome caused by mosaic trisomy 15. Am J Med Genet 62:109–112. Codwell S, Fitzgerald B, Semmens JM, Ede R, Bateman C (1981). A case of trisomy of chromosome 15. J Med Genet 18:146–148. Fryns JP, Kleczkowska A, Lagae L, Kenis H, van den Berghe H (1993). A specific phenotype associated with trisomy 15 mosaicism. Ann Genet 36:129–131. Kuller JA, Laifer SA (1991). Trisomy 15 associated with nonimmune hydrops. Am J Perinatol 8:39–40. Lahdetie J, Lakkala T (1992). Mosaic trisomy found at amniocentesis. Prenat Diagn 12:551–552. Milunsky JM, Wyandt HE, Huang XL, Kang XZ, Elias ER, Milunsky A (1996). Trisomy 15 mosaicism and uniparental disomy (UDP) in a liveborn infant. Am J Med Genet 61:269–273. Olander E, Stamnerg J, Steinberg L, Wulfsberg EA (2000). Third Prader–Willi syndrome phenotype due to maternal uniparental disomy 15 with trisomy 15. Am J Med Genet 93:215–218. Prontera P, Buldini B, Aiello V, Gruppioni R, Bonfatti A, Venti G, Ferlini A, et al. (2006). Trisomy 15 mosaicism owing to familial reciprocal translocation t(1;15): implication for prenatal diagnosis. Prenat Diagn 26:571–576. Stallard R, Sommer A (1989). Trisomy 15 in a mosaic, doubly aneuploid two year old. Am J Hum Genet 45 (Suppl):A92. Zaragoza MV, Jacobs PA, James RS, Rogan P, Sherman S, Hassold T (1994). Nondisjunction of human acrocentric chromosomes: studies of 432 trisomic fetuses and liveborns. Hum Genet 94:411–417. Zaslav AL, Fallet S, Brown S, Ebert R, Fleischer A, Valderama E, Fox JE (1998). Prenatal diagnosis of low level trisomy 15 mosaicism: review of the literature. Clin Genet 53:286–292.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
An infant with trisomy 15 mosaicism Sedat Isıkay and Kursat B. Carman Clinical Dysmorphology 2013, 22:172–174 Department of Pediatric Neurology, Gaziantep Children’s Hospital, Gaziantep, Turkey
Correspondence to Kursat B. Carman, MD, Gaziantep Children’s Hospital, Gaziantep 27000, Turkey Tel: + 90 342 360 0888; fax: + 90 342 360 0890; e-mail: [email protected] Received 25 January 2013 Accepted 8 August 2013
List of key features Trisomy 15 mosaicism Minor facial abnormalities Anterior anus
Introduction Conceptions with autosomal trisomies are usually aborted spontaneously in the first trimester of pregnancy. Trisomy 15 accounts for 7.6% of all trisomic abortions and 1.68% of all first-trimester pregnancy losses (Prontera et al., 2006). Few cases of mosaic trisomy 15 in liveborn infants have been reported (Codwell et al., 1981; Stallard and Sommer, 1989; Kuller and Laifer, 1991; Lahdetie and Lakkala, 1992; Fryns et al., 1993; Bu ¨hler et al., 1996; Milunsky et al., 1996; Zaslav et al., 1998; Olander et al., 2000; Prontera
et al., 2006). We report here the clinical features of an infant with mosaicism for trisomy 15.
Case report A 2-month-old girl was admitted to the paediatric neurology unit because she had marked hypotonia. She was born by Caesarean section at 38 weeks of gestation after a normal pregnancy and was the first child born to first-cousin parents; the mother was aged 32 years at her birth. Physical and neurological examination revealed a head circumference of 37 cm (25th–50th percentiles), height of 54 cm (10th–25th percentiles), and weight of 4.5 kg (25th–50th percentiles). Her muscle tone was hypotonic and deep tendon reflexes were hypoactive. Talipes equinovarus was noticed on both feet. The patient had trigonocephaly with a prominent forehead,
Fig. 2 Fig. 1
Dysmorphic facial features of infant. c 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins 0962-8827
Discrete depression on the posterior surface of the helical rim of ear.
DOI: 10.1097/MCD.0000000000000012
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
An infant with trisomy 15 mosaicism Isıkay and Carman 173
small palpebral fissures, wide epicanthic folds, a broad flat nasal bridge, a small mouth, a high arched palate, and micrognathia (Fig. 1). The ears were low-set and there Fig. 3
were several discrete depressions on the posterior surfaces of the helical rim of both ears (Fig. 2). A transverse palmar crease was present on her right hand. She had anterior placement of her anus (Fig. 3). Laboratory investigations including complete blood count, biochemical studies, and thyroid function tests yielded normal results. Brain MRI, echocardiography, and abdominal ultrasonography also produced normal findings. Cytogenetic analysis of her peripheral blood revealed a mosaic 46,XX/47,XX, + 15 karyotype (Fig. 4). After the initial analysis, we increased the metaphase count up to 100, which showed the abnormal karyotype to be present in 30 of 100 cells.
Discussion We report a liveborn patient with trisomy 15 mosaicism. She presented with hypotonia and dysmorphic features. Trisomy 15 mosaicism is rarely reported and there have been only nine documented liveborn cases (Codwell et al., 1981; Stallard and Sommer, 1989; Kuller and Laifer, 1991; Lahdetie and Lakkala, 1992; Fryns et al., 1993; Bu ¨hler
Anterior placement of anus.
Fig. 4
1
2
3
6
7
8
13
14
15
19
20
4
9
21
5
10
11
12
16
17
18
22
X
Y
Cytogenetic analysis indicating trismony 15.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
174 Clinical Dysmorphology 2013, Vol 22 No 4
Table 1
Clinical and radiologic some features of patients with trisomy 15 mosaicism Codwell Stallard and Kuller and Lahdetie and Fryns et al. Bu¨hler et al. Milunsky Olander Prontera et al. (1981) Sommer (1989) Laifer (1991) Lakkala (1992) (1993) (1996) et al. (1996) et al. (2000) et al. (2006)
Sex Female Newborn Age at examination Developmental + delay Broad nasal + bridge Upturned nose – Large + prominent nose Small mouth + Micrognathia/ + retrognathia Abnormal ears + Abnormal ribs + Talipes + equinovarus Anteriorly + placed anus Congenital + heart disease
Male 6 months
Male Newborn
Female Newborn
Female 3 months
Male 1 month
Female Newborn
Male Newborn
Female 4 years
This study Female 1 month
+
+
+
+
–
+
+
+
+
+
+
–
+
+
+
+
+
+
+ –
– +
– –
+ +
+ +
+ +
– –
– –
+ +
– –
+ –
– –
+ +
+ +
+ +
– +
+ +
+ +
– NA –
– – –
– – –
– – –
– + +
+ + –
+ – –
– + –
+ – +
–
–
–
+
–
+
–
–
+
–
–
+
+
–
+
+
–
–
NA, not available.
et al., 1996; Milunsky et al., 1996; Olander et al., 2000; Prontera et al., 2006). The most consistent clinical characteristics of trisomy 15 mosaics are minor facial anomalies and congenital heart disease. Ventricular septal defect, patent foramen ovale, and patent ductus arteriosus have all been reported (Zaslav et al., 1998). However, the echocardiographic investigation of our patient revealed normal findings. Some clinical and radiological features of previous cases are listed in Table 1. Trisomy 15 is usually associated with advanced maternal age. In previous cases, when the parent of origin was studied, most cases occurred as a result of nondisjunction in maternal meiosis I (Zaragoza et al., 1994). In the present case, the mother was 32 years old. Unfortunately, we were not able to show the origin of trisomy in our patient. The origin of the mosaicism may have been due to a trisomic conception undergoing subsequent ‘trisomy rescue’ resulting in a trisomic and apparently normal cell line. Some of these occurrences are associated with uniparental disomy in the apparently normal cell line, which may give rise to features of Prader–Willi or Angelman syndrome depending on parental origin. Apart from hypotonia there were no convincing features of these disorders in our patient. Alternatively, the mosaicism may have resulted from a mitotic error. We were not able to test our patient further to explore the origins of the mosaicism, although we think the most likely origin is either a mitotic error in an originally normal conception or trisomy rescue, resulting in a trisomic cell line and a normal cell line with both a paternal and maternal chromosome 15, as the child had abnormalities in keeping with previously reported cases (Zaslav et al., 1998).
In conclusion, we report a case with trisomy 15 mosaicism. It should be considered in the differential diagnosis of patients presenting with hypotonia and dysmorphic features.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References Bu¨hler EM, Bienz G, Straumann E, Bo¨sch N (1996). Delineation of a clinical syndrome caused by mosaic trisomy 15. Am J Med Genet 62:109–112. Codwell S, Fitzgerald B, Semmens JM, Ede R, Bateman C (1981). A case of trisomy of chromosome 15. J Med Genet 18:146–148. Fryns JP, Kleczkowska A, Lagae L, Kenis H, van den Berghe H (1993). A specific phenotype associated with trisomy 15 mosaicism. Ann Genet 36:129–131. Kuller JA, Laifer SA (1991). Trisomy 15 associated with nonimmune hydrops. Am J Perinatol 8:39–40. Lahdetie J, Lakkala T (1992). Mosaic trisomy found at amniocentesis. Prenat Diagn 12:551–552. Milunsky JM, Wyandt HE, Huang XL, Kang XZ, Elias ER, Milunsky A (1996). Trisomy 15 mosaicism and uniparental disomy (UDP) in a liveborn infant. Am J Med Genet 61:269–273. Olander E, Stamnerg J, Steinberg L, Wulfsberg EA (2000). Third Prader–Willi syndrome phenotype due to maternal uniparental disomy 15 with trisomy 15. Am J Med Genet 93:215–218. Prontera P, Buldini B, Aiello V, Gruppioni R, Bonfatti A, Venti G, Ferlini A, et al. (2006). Trisomy 15 mosaicism owing to familial reciprocal translocation t(1;15): implication for prenatal diagnosis. Prenat Diagn 26:571–576. Stallard R, Sommer A (1989). Trisomy 15 in a mosaic, doubly aneuploid two year old. Am J Hum Genet 45 (Suppl):A92. Zaragoza MV, Jacobs PA, James RS, Rogan P, Sherman S, Hassold T (1994). Nondisjunction of human acrocentric chromosomes: studies of 432 trisomic fetuses and liveborns. Hum Genet 94:411–417. Zaslav AL, Fallet S, Brown S, Ebert R, Fleischer A, Valderama E, Fox JE (1998). Prenatal diagnosis of low level trisomy 15 mosaicism: review of the literature. Clin Genet 53:286–292.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
