Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome-wide copy number analysis in 82 patients without imprinting defects

Inoue, Takanobu; Nakamura, Akie; Fuke, Tomoko; Yamazawa, Kazuki; Sano, Shinichiro; Matsubara, Keiko; Mizuno, Seiji; Matsukura, Yoshika; Harashima, Chie; Hasegawa, Tatsuji; Nakajima, Hisakazu; Tsumura, Kumi; Kizaki, Zenro; Oka, Akira; Ogata, Tsutomu; Fukami, Maki; Kagami, Masayo

doi:10.1186/s13148-017-0350-6

Table 1 Clinical features of three SRS-compatible and two SRS-like patients with PCNVs

From: Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome-wide copy number analysis in 82 patients without imprinting defects

	SRS-compatible			SRS-like
Patient	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Genetic cause	4p16.3 deletion	Mosaic trisomy 18	19q13.11-12 deletion	7q11.23 deletion
Karyotype	46,XX	46,XY [14]/47,XY,+18 [6]	46,XX	46,XY	NE
Sex	Female	Male	Female	Male	Female
Present age (years)	9	1 9/12	4	19	7
Gestational age (weeks:days)	34:1	40:4	34:3	40:0	40:5
Birth length in cm (SDS)^a	38 (−2.37)	41 (−4.60)	37.5 (−2.62)	45 (−2.36)	45 (−2.61)
Birth weight in g (SDS)^a	1246 (−3.13)	1700 (−4.80)	1156 (−3.67)	2734 (−1.45)	2276 (−2.91)
Birth OFC in cm (SDS)^a	27.0 (–2.17)	31.0 (−1.96)	24.0 (−3.79)	32.5 (−0.69)	32.4 (−0.92)
Height at 24 months in cm (SDS)^{b, c}	70 (−4.87)	・・・	74.8 (−3.63)	85.2 (−3.06)	72.3 (−3.66)
BMI at 24 months (SDS)^{b, c}	−3.34	・・・	−4.18	+0.27	+1.00
Present height in cm (SDS)^b	104.5 (−3.82) at 8 years	73.3 (−3.38)	86.1 (−3.28) at 3 10/12 years	156.4 (−2.38) at 16 years	106.0 (−2.64)
Present weight in kg (SDS)^b	11.6 (−7.86) at 8 years	8.77 (−2.28)	8.9 (−5.06) at 3 years	50.8 (−1.25) at 16 years	20.3 (−0.58)
Present OFC in cm (SDS)^b	46.1 (−4.29) at 8 years	47.8 (+0.20) at 1 7/12 years	42.5 (−3.96) at 2 years	Unknown	Unknown
GH treatment	−	−	3 1/12 years~	5 ~ 16 years	−
SGA^d	+	+	+	+	+
Postnatal growth failure^{c, e}	+	・・・	+	+	+
Relative macrocephaly at birth^f	−	+	−	+	+
Protruding forehead	+	+	+	−	−
Body asymmetry	−	+	−	−	−
Feeding difficulties and/or low BMI	+	+	+	−	−
NH-CSS	4/6	5/5	4/6	3/6	3/6
Triangular face	+	+	+	+	+
Fifth finger clinodactyly	−	−	−	−	+
Fifth finger brachydactyly	−	−	+	+	+
Present characteristic features of genetic syndrome caused by PCNV	Pre- and postnatal growth failure, Protruding forehead, Tube feeding, Greek warrior helmet appearance, Severe global developmental delay, Atrial septal defect, Epilepsy, Hearing loss	Prenatal growth failure, Tube feeding, Ventricular septal defect	Pre- and postnatal growth failure, Slender habitus, Long face, Cutis aplasia (posterior occiput), Moderate global developmental delay	Pre- and postnatal growth failure, Long philtrum, Medial eyebrow flare, Moderate global developmental delay	Pre- and postnatal growth failure, Prominent lips with open mouth, Hearing loss, Fifth finger clinodactyly, Moderate global developmental delay
Absent characteristic features of genetic syndrome caused by PCNV	Distinct mouth, Short philtrum	Overlapping fingers, Rocker bottom feet, Apnea, Single umbilical artery, Prominent occiput, Microcephaly, Inguinal hernia Umbilical hernia, Cleft lip, Cleft palate	Microcephaly	Prominent lips with open mouth, Hearing loss, Fifth finger clinodactyly, Cardiovascular anomalies, Hypercalcemia, Periorbital fullness, Joint hypermobility, Soft lax skin	Long philtrum, Medial eyebrow flare, Cardiovascular anomalies, Hypercalcemia, Periorbital fullness, Joint hypermobility, Soft lax skin
Congenital heart disease	Atrial septal defect	Ventricular septal defect	−	−	−
Development
Motor developmental delay	+	−	+	+	+
Age at head control (months)	Unknown	4	7	Unknown	3
Age at sitting without support (months)	−	6	9	Unknown	10
Age at walking without support (months)	−	14	26	Unknown	24
Speech delay	+	+	+	+	+
IQ/DQ (age at examination)	10 (9 years)	78 (1 9/12 years)	50 (2 10/12 years)	50 (8 years)	50 (5 years)
Other findings	Severe neonatal asphyxia, Periventricular leukomalacia	−	−	−	−

SRS Silver-Russell syndrome, PCNV pathogenic copy number variation, NE not examined, SDS standard deviation score, OFC occipitofrontal circumference, BMI body mass index, GH growth hormone, SGA small for gestational age, NH-CSS Netchine-Harbison clinical scoring system, IQ intelligence quotient, DQ developmental quotient
^aBirth length, weight and OFC were evaluated by the sex- and the gestational age-matched Japanese reference data (http://jspe.umin.jp/medical/keisan.html).
^bPostnatal height, BMI, weight and OFC were evaluated by the sex- and the age-matched Japanese reference data (http://jspe.umin.jp/medical/keisan.html) (http://jspe.umin.jp/medical/taikaku.html).
^cIf we did not get information at 24 ± 1 months, we used the data at the nearest measure available older than 25 months.
^dBirth length and/or birth weight ≤–2 SDS.
^eHeight at 24 ± 1 months ≤–2 SDS or height ≤ –2 SDS below mid-parental target height. Mid-parental target height was calculated as follows: [(father’s height + mother’s height)/2] +6.5 cm for boys and –6.5 cm for girls.
^fHead circumference at birth ≥1.5 SDS above birth length and/or weight SDS.

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ISSN: 1868-7083

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