Table 1.
Phenotype of Individuals with MFDM
|
Individual |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | |
| Reference | this report | Wieczorek5, “patient 2” | Wieczorek5, “patient 3” | Guion-Almeida4, “patient 2” | this report | this report | Wieczorek5, “patient 1” | this report | Guion-Almeida4, “patient 1” | this report | this report | this report |
| Inheritance | sporadic | sporadic | sporadic | sporadic | sporadic | sporadic | sporadic | sporadic | sporadic | sporadic | sporadic | sporadic |
| Sex | M | M | F | M | F | M | F | F | M | M | F | M |
| Consanguinity | - | - | - | - | - | - | - | - | + (f = 1/16) | - | - | - |
| Paternal age (years) | 35 | N/R | N/R | 28 | N/R | 26 | N/R | 31 | 25 | N/R | N/R | N/R |
| Pregnancy complications | N/R | N/R | increased NT and microcephaly | N/R | IUGR | N/R | PROM | - | - | - | polyhydramnios | increased NT |
| Gestation (weeks) | 37 | 42 | 39 | full term (number of weeks not available) | 40 | 39 | 33 | 41+3 | full term (number of weeks not available) | 40 | 41+4 | 42 |
| Birth weight (g) | 2,150 (−2 SD) | 3,180 (−1.5 SD) | 2,850 (−1.25 SD) | 3,100 | 2,610 (−2 SD) | 2,400 (−2.5 SD) | 1,500 (−1.5 SD) | 3,870 (+0.5 SD) | 3,500 | 3,000 (−1 SD) | 3,330 (−1 SD) | 3,161 (−1.5 SD) |
| Birth head circumference (cm) | 30.5 (−1.75 SD) | 33 (−2 SD) | 30 (−3 SD) | N/R | 31 (−2.75 SD) | N/R | 27 (−2 SD) | 32.5 (−2 SD) | N/R | 33 (−1 SD) | 31 (−3.5 SD) | N/R |
| Age at last assessment | 3 years | 7 years, 8 months | 6 years, 5 months | 9 years, 5 months | 2 years, 7 months | 1 year, 2 months | 7 years, 2 months | 2 years | 13 years, 4 months | 2 years, 5 months | 1 year | 7 years, 2 months |
| Head circumference (cm) | (−3.5 SD) | 47 (−3.5 SD) | 43.8 (−5 SD) | 48 (−3.5 SD) | 43.5 (−4 SD) | 43 (−3 SD) | 42.5 (−6 SD) | 42 (−5 SD) | 50 (−3 SD) | 44.5 (−4 SD) | 39.8 (−5 SD) | 46.4 (4 years, 9 months) (−3 SD) |
| Weight (kg) | normal | 24 (+0 SD) | 22.5 (+0 SD) | 24 (−2 SD) | 13.4 (+0 SD) | 8 (−3.5 SD) | 24 (+0 SD) | 10.3 (−2 SD) | 38 (−1.5 SD) | 12.7 (−0.75 SD) | 6.72 (−4 SD) | 22.6 (7 years, 2 months) (+0 SD) |
| Height (cm) | normal | 122 (−1 SD) | 117.4 (+0 SD) | 131 (−1 SD) | 87 (−1.75) | 71 (−3 SD) | 118 (−1 SD) | 84 (−0.25 SD) | 151 (−1.25 SD) | 89 (−0.75 SD) | 69 (−2 SD) | 116.6 (7 years, 2 months) (−1.5 SD) |
| Malar hypoplasia | + | + | + | + | + | + | + | + | + | + | - | + |
| Micrognathia | + | + | + | + | + | + | + | + | + | + | + | + |
| Obliquity of palpebrae | upslanting | upslanting | level | one downslanting | upslanting | downslanting | upslanting | downslanting | + | level | level | level |
| Lower-eyelid cleft | - | + | - | - | - | - | - | - | - | + | bilateral | - |
| Microtia | + | + | + | + | + | + | + | + | + | + | + | N/R |
| Preauricular tags | + | unilateral | bilateral | + | unilateral | unilateral | unilateral | - | + | unilateral | - | unilateral |
| Auditory canal atresia or stenosis | N/R | bilateral | unilateral | - | unilateral | N/R | bilateral | + | - | bilateral | unilateral | - |
| Hearing loss | conductive | conductive | conductive | N/A | conductive | sensorineural | conductive | conductive | - | conductive | conductive | conductive |
| Midline cleft palate (including submucous) | - | + | - | + | + | bifid uvula | - | - | + | + | + | - |
| Choanal atresia | + | bilateral | unilateral | - | N/R | N/R | bilateral | bilateral | - | - | - | bilateral |
| Need for neonatal resuscitation | + | - | - | - | - | + | + | - | - | - | - | - |
| Tracheostomy | + | - | - | - | - | - | - | - | - | - | - | - |
| Global developmental delay | + | mild to moderate | mild | moderate to severe | moderate to severe | + | moderate | moderate | severe | mild to moderate | mild to moderate | moderate |
| Age at walking (months) | 28 | 16 | 24 | 17 | 24–36 | N/R | 24 | 24 | 60 | 19 | NM | 19 |
| Age at first words (months) | NM | 24 | 20 | 24 | NM | N/R | 30 | NM | NM | NM | NM | N/R |
| Brain MRI | normal | delayed myelination at 15 months of age | normal | N/R | N/R | N/R | N/R | N/R | N/R | abnormal white matter on FLAIR | N/R | N/R |
| Seizures | N/R | + | - | + | - | N/R | + | - | + | + | - | - |
| Gastrostomy | + | - | + | - | - | - | - | - | - | N/R | - | - |
| Metopic ridge | + | + | - | + | + | + | - | - | + | N/R | - | + |
| Congenital heart defect | - | ASD | - | - | VSD | ASD | mild PPS | - | ASD | ASD | ASD | - |
| Proximally placed thumb | + | - | + | N/R | N/R | + | - | - | N/R | N/R | - | + |
| Duplicated thumb | - | - | - | - | - | - | - | - | + | N/R | - | - |
| Other anomalies | cryptorchidism and small scrotum | hypoplastic toenails and delayed bone age | myopia, middle ear and vestibular hypoplasia | - | - | cryptorchidism and small scrotum | - | - | - | N/R | - | - |
| Karyotype | 46,XY | N/R | 46,XX | 46,XY | 46,XX | N/R | 46,XX | 46,XX | 46,XY | 46,XY | 46,XX | 46,XY |
| Microarray (hg19) | see Table 2 | normal | N/R | N/R | see Table 2 | N/R | N/R | normal | N/R | normal | N/R | normal |
| EFTUD2 mutation (see Table 2) | deletion of last nine exons | p.Arg262Trp | p.Gln924∗ | p.Ser586fs∗19 | complex rearrangement causing deletion | p.Arg262fs∗1 | p.Ser391fs∗57 | p.Gln719∗ | p.Tyr831∗ | intron 16 5′ splice site | p.Leu637Arg | p.Cys476Arg |
Abbreviations are as follows: N/R, not reported; NT, nuchal translucency; IUGR, intrauterine growth restriction; PROM, premature rupture of membranes; N/A, not assessed; NM, milestone not yet met; FLAIR, fluid attenuated inversion recovery; ASD, atrial septal defect; VSD, ventricular septal defect; and PPS, peripheral pulmonic stenosis.