Table 1.

Dysmorphic, neurological, osteoarticular, cardiac and ectodermal features, and neoplasias in the subjects with Costello syndrome, heterozygous for the c.34G>A missense change (Gly12Ser) in HRAS, included in the study

	Features
	Patient 1	Patient 2	Patient 3	Patient 4	Patient 5
Sex	F	M	F	F	F
Age (years)	15	16	24	24	14
Growth*
OFC (s.d.)	0	+2	0	−2	+1
Height (s.d.)	−4,5	−4,5	−4,5	−6	−6
Weight (s.d.)	−3,5	−3,5	−3,5	−4	−3
Facial
‘Coarse’ face	+	+	+	+	+
Epicanthus	+	+	+	+	+
Strabismus	+	+	+	+	−
Depressed and wide nasal bridge	+	+	+	+	+
Bulbous tip of nose	+	−	+	+	+
Fleshy and cocked auricular lobes	+	+	+	+	+
Low set/posteriorly angulated ears	+	+	+	+	+
Full cheeks	+	+	+	+	+
Macrostomy/thick lips	+	+	+	+	+
Hoarse and deep voice	+	+	+	+	+
Mental development (IQ)	52a	41a	52a	48a	51a
Dystonia (GDS/UDRS)	8/6	7/5	12/9	−	6/4
Epilepsy	−	−	−	−	−
MRI anomalies	−	−	Ch	−	Ch
Long Term Memory
Verbal learning (IR/DR)	9°/9°	16°/25°	<1/2°	2°/5°	1°/2°
Visual learning (IR/DR)	1°/<1°	<1°/1°	<1°/<1°	<1°/9°	16°/2°
Spatial learning (IR/DR)	2°/9°	5°/5°	9°/1°	25°/37°	16°/5°
Mental age	6.8	7.8	12.2	11.0	7.0
Heart
Hypertrophic cardiomiopathy	+	+	+	+	+
Valvular anomalies	−	−	MVP	PVS	−
Arrhythmias	PAC	PVC	−	rBBB	−
Osteoarticular
Short neck	+	+	+	+	+
Ulnar deviation of fingers	+	+	+	+	+
Interphalangeal laxity of fingers	+	+	+	+	+
Limited extension of joints	H, A	E, H, A	E, H, A	E, A	E
Spine	Hl	K	Hl, S	S	S
Skin and adnexa
Deep palmar and plantar creases	+	+	+	+	+
Dark pigmentation	+	+	+	+	+
Thin dystrophic nails	+	+	+	+	+
Redundant skin	+	+	+	+	+
Hyperkeratosis	−	+	+	+	+
Curly hair	+	+	+	+	+
Neoplasias
Papillomata	+	+	+	+	−
Other neoplasias	−	+	+	+	−

^*Growth parameters referred to time of examination; A, Achilles tendon; Ch: Chiari 1 malformation; E, elbow; H, hip; Hl, hyperlordosis; Hy: hydrocephalus; IQ, intelligence quotient; MVP: mitral valve prolapse; PVS: pulmonary valve stenosis; PAC: premature atrial contraction; PVC: premature ventricular contraction; rBBB: right bundle brunch block; K, kyphoscoliosis; MRI: magnetic resonance imaging; S, scoliosis. IR, immediate recall. DR, delayed recall.

^aWechsler intelligence scale. GDS, Global Dystonia Scale. UDRS, Unified Dystonia Rating Scale. OFC, Occipitoprontal circumference. S.D. standard deviations from standard median valves based on centers for disease control and prevention (CDC) Sex-specific OFC, height and weight-for-age growth charts.