Table 1

Detailed phenotypic description of the seven tested patients

Patient	1	2	3	4	5	6	7
FGFR1 mutation	c.494T>C p.L165S*	c.572T>C p.L191S*	c.1468G>C p.G490R	c.1867G>T p.D623Y	c.1884 T>G p.N628K	c.2174 G>A p.C725Y	–
Sex	M	M	M	F	M	M	F
Previous report⁵	Patient 3	–	Patient 5	–	Patient 2	Patient 4	–
Consanguinity	+	−†	−	−	−	−	−
Brain
HPE	AL	L	SL	L	SL	L	AL
CCA	+	+	nr	Partial	Partial	Partial	nr
Pituitary	Normal	nr	nr	nr	Normal	Normal	nr
Diminished cortical thickness	+	+	−	−	−	−	+‡
Face
CLP	Median	–	Bilateral	–	Bilateral	–	Cleft palate only
Eye	Hypotelorism	Hypotelorism	hypertelorism	Normal	Normal	Normal	Hypertelorism§
Hands
Ectrodactyly	+	+	+	−	+	+	+
Digit number (right/left)	2/2	3/3	3/3	5/5	4/4	5/5	2/3
Other		6 metacarpal bones on the left side, with partial fusion of the 4th and 5th	Bifurcation of the thumbs		Fused 2nd and 3rd metacarpal bones		Forearm hypoplasia
Feet
Ectrodactyly	+	+	+	+¶	+	+	−
Digit number (right/left)	1/1	2/2	2/2	5/5	2/3	4/3	5/5
Other			Equinovarus deformity
Pituitary insufficiency	nr	nr	nr	CDI, HH, normal GH secretion, low response to TRH	CDI, HH	CDI, HH, normal GH secretion	nr
Genitalia	Normal	nr	Micropenis, cryptorchidism	Normal	Micropenis, cryptorchidism	Micropenis, cryptorchidism	Normal
Growth retardation	+	+	+	+ Good response to GH treatment	+ 160 cm (target: 176.5±8.5 cm)	+ 161.6 cm (target: 172.5±8.5 cm)	nr
DD/ID	Severe	Severe	Severe	Mild	Moderate	Mild	na
other	Generalised hypertonia, no smile, seizures (grand mal)	No language, spasticity	No language, wheelchair bound		Wheelchair bound (spastic paraplegia)	IQ 63 (Stanford-Binet score), at 6 years 8 months
Follow-up	Died at the age of 5 years	Died at the age of 4 years (respiratory infection)		Mainstream school with support	Lives in an institution	Works in a sheltered workshop	TOP

Positions of the mutations refer to coding DNA reference sequence CCDS6107.2 and Uniprot protein sequence P11362-1.
*Homozygous mutations.
†Low level consanguinity could not be assessed, the parents being lost to follow-up.
‡Patient 7 has severe microcephaly (head circumference of 15 cm at 20 weeks), hydrocephaly, and severe disruption of the telencephalic architecture.
§Patient 7 has severe facial anomalies: absence of nasal wing on the right side, right microphthalmia and eye defect.
¶Patient 4: Left foot: fusion of first and second toes, large gap between second and third rays, syndactyly of toes 3–5, absence of the third phalange of digits 3 and 4. Right foot: central large gap with partial syndactyly of toes 3–5, absence of the third phalange of digits 2 and 3.
AL, alobar; CCA, corpus callosum agenesis; CDI, central diabetes insipidus; CLP, cleft lip and palate; DD, developmental delay; F, female; GH, growth hormone; HH, hypogonadotropic hypogonadism; HPE, holoprosencephaly; ID, intellectual disability; L, lobar; M, male; na, not applicable; nr, not reported; SL, semilobar; TOP, termination of pregnancy; TRH, thyrotropin releasing hormone.