Mutation in NRAS in familial Noonan syndrome – case report and review of the literature

Ekvall, Sara; Wilbe, Maria; Dahlgren, Jovanna; Legius, Eric; van Haeringen, Arie; Westphal, Otto; Annerén, Göran; Bondeson, Marie-Louise

doi:10.1186/s12881-015-0239-1

BMC Medical Genetics

Table 2 Clinical features of patients with Noonan syndrome caused by NRAS mutations

From: Mutation in NRAS in familial Noonan syndrome – case report and review of the literature

#	1	2	3	4	5	6	7	8	9	9 M	10	11	12	12 F
Patient	De Filippi et al. [20]	Runtuwene et al. [21]	Denayer et al. [22]	Denayer et al. [22]	Denayer et al. [22]	Cirstea et al. [14]	Cirstea et al. [14]	Cirstea et al. [14]	Cirstea et al. [14]	Cirstea et al. [14]	Kraoua et al. [23]	Kraoua et al. [23]	Present study	Present study
NRAS mutation	p.G13D	p.I24N	p.I24N	p.P24L	p.T50I	p.T50I	p.T50I	p.G60E	p.G60E	p.G60E	p.G60E	p.G60E	p.G60E	p.G60E
Origin of mutation	de novo	de novo	de novo	Inherited	ND	de novo	de novo	de novo	Inherited	ND	ND (probably inherited)	de novo	Inherited	ND (probably inherited)
Paternal age at conception	ND	26 years	ND	ND	ND	50 years	34 years	31 years	47 years	44 years	45 years	47 years	34 years	ND
Age at last examination	3 years	30 years	13 years	19 years	2.5 years	14 years	7 years	3.3 years	20 years	50 years	24 years	3 months	28 years	62 years
Gender	Male	Male	Male	Male	Male	Male	Male	Female	Male	Female	Male	Female	Female	Male
Prenatal findings	ND	Polyhydramnios	ND	ND	ND	Nuchal edema, Polyhydramnios	Polyhydramnios	Single umbilical artery	-	-	Polyhydramnios	Pyelectasis	-	-
Congenital heart defect	-	-	-	ND	Coarctation aortae, Patent foramen ovale	HCM	PS	Mild HCM, Mitral valve dysplasia, PS	-	-	-	PS	ASD, HCM	Cardiac murmur
Rythm disturbance	ND	-	ND	ND	-	SVES	-	-	-	-	-	-	-	-
Typical facial features	+	+	+	+	+	+	+	+	+	+	+	+	+	+
Stature	5–10^th centile	Mild short	<3^rd centile	10^th–25^th centile	10^th–25^th centile	10^th centile^a	<3^rd centile	<3^rd centile	>10^th centile	10^th centile	3^rd centile	3^rd–10^th centile	50^th centile^a	50^th centile
Macrocephaly	Relative	>90^th centile	>97^th centile	ND	25^th–50^th centile	+	Relative	-	+	+	Relative	Relative	+	Relative
Pterygium colli/Webbed neck	-	+	ND	ND	+	+	-	+	+	+	+	+	+	+
Thorax deformity	-	Pectus excavatum	Pectus excavatum	ND	Pectus excavatum	+	-	Pectus excavatum	+	+	Mildly depressed thorax	Pectus excavatum	-	-
Easy bruising	-	-	ND	+	ND	-	-	-	-	-	+	ND	+	-
Cryptorchidism	-	+	+	ND	+	+	+	NA	+	NA	-	NA	NA	-
Ophthalmological problems	ND	-	Strabismus, Bilateral keratoconus of the cornea	ND	ND	Myopia	-	-	-	Myopia	-	-	Astigmatis, Myopia, Strabismus	-
Motor delay/Muscular hypotonia	-	Motor delay	Mild	ND	ND	Mild	+	+	+	+	Mild	+	-	-
Mental development	Normal	Mild learning difficulties	Normal	Learning difficulties	Normal	Normal	Borderline	Speech delay	Normal-borderline	Normal	Speech delay, dyscalculy	NA	ADHD, normal IQ	Normal
Keratosis pilaris/Hyperkeratosis	ND	-	ND	ND	ND	Severe	-	+	+	+	ND	-	-	-
Hair abnormalities	-	-	ND	ND	ND	Curly hair	Curly hair	Sparse thin hair	Curly hair	-	-	Curly hair	-	Curly hair
Lentigines/Café-au-lait spots	+	Some lentigines	-	-	-	-	-	-	-	-	+	+	+	+
Leukemia/Cancer	JMML	-	-	-	-	-	-	-	-	-	-	-	-	-
Other	-	Oligospermia	-	Inadequate visio-spatial orientation skills, Inguinal hernia, Delayed pubertal development	-	Pes equinovarus	-	Palpebral ptosis	Ichtyosiform eczema, Acanthosis nigricans, Scoliosis	Mother of patient 9	Palpebral ptosis, Inguinal hernia, Scoliosis	Palpebral ptosis, Unilateral pyelectasis	-	Sensory-neural hearing deficit, Father of patient 12

ASD atrial septal defect, HCM hypertrophic cardiomyopathy, JMML juvenile myelomonocytic leukemia, NA not applicable, ND not determined, PS pulmonic stenosis, SVES supraventricular extrasystole
^aReceived growth hormone treatment from the age of 8 years, when partial growth hormone deficiency had been noted

Back to article page

ISSN: 1471-2350

Contact us

General enquiries: ORSupport@springernature.com