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.