Table 1.
Clinical findings in five families with mutations in FAM50A.
| Individual | K8100 IV-1 | K8100 IV-2 | K9648 II-3 | K9656 II-1 | K9667 II-2 | K9677 II-1 |
|---|---|---|---|---|---|---|
| FAM50A variant | c.764A>G; p.Asp255Gly | c.764A>G; p.Asp255Gly | c.616T>G; p.Trp206Gly | c.761A>G; p.Glu254Gly (de novo) | c.817C>T; p.Arg273Trp (de novo) | c.763G>A; p.Asp255Asn (de novo) |
| Ethnicity | Caucasian | Caucasian | Mixed (African-American, Middle Eastern, Mixed European) | Caucasian | Caucasian | Caucasian |
| Clinical characteristics | ||||||
| Growth | ||||||
| Birth (gestational weeks) | 40 | 40 | 34 | 35 | 38.5 | ND |
| Length, cm (%) | 47 (5) | 45.7 (<3) | 43.2 (15) | 47 (50) | 48.3 (25) | 53.3 (95) |
| Weight, kg (%) | 3.2 (30) | 2.9 (15) | 2.4 (60) | 2.5 (40) | 2.8 (20) | 4.4 (97) |
| HC, cm (%) | 36.2 (55) | 36 (50) | NA | NA | 34.3 (20) | 39 (>97) |
| Postnatal (years–months) | 28 | 24 | 7–10 | 9–7 | 8–3 | 25–10 |
| Height, cm (%) | 154.9 (<3) | 154.9 (<3) | 106.2 (<3) | 120.5 (<3) | 122 (9) | 160.5 (<3) |
| Weight, kg (%) | 70 (15) | 43.2 (<3) | 19.4 (<3) | 38.4 (85) | 27.9 (63) | 61.9 (<3) |
| HC, cm (%) | 58.6 (85) | 58.5 (85) | 50.2 (5) | 54 (75) | 52.1 (30) | 60.25 (>97) |
| Development | ||||||
| Delay | Global, special education, ambulatory, speaks in short phrases | Global, special education, ambulatory (walked at 3 yrs) single words | Global, not ambulatory, no speech | Global, regular classes with support | Global, no speech, special education, ambulatory for short distances | Global |
| IQ | 66 | ND | ND | ND | <50 | 63 |
| Somatic findings | ||||||
| Craniofacial | Macrocephaly, epicanthal folds, depressed nasal bridge, downslanted palpebral fissures, cleft palate, bow-shaped mouth, microretrognathia | Broad forehead, epicanthal folds, depressed nasal bridge, downslanted palpebral fissures, low-set ears, micrognathia | Prominent forehead, bitemporal narrowing, proptosis, hypotelorism, tubular nose, single median incisor, hypodontia, low-set ears, large left ear, prominent lips | Bilateral epicanthal folds, infraorbital creases, wide nasal root, short and lightly upturned nose with underdeveloped nares, slightly posteriorly rotated ears, faint hemangiomas between brows and at back of neck | Bulbous nose, excessively folded helices | Prominent tall forehead, overfolded helices, micrognathia |
| Ocular | Strabismus | — | Axenfeld–Rieger with glaucoma, nystagmus | Strabismus | Exotropia | Exotropia, keratoconus, nystagmus |
| Cardiac | ASD, PDA | — | Tetralogy of Fallot, right ventricle dilation | ASD | — | — |
| Skeletal | Small feet, pes cavus, hammertoes | Small feet, pes cavus, hammertoes | Small hands/feet, short limbs, crease across dorsum of feet, foot eversion/inversion, coxa valga, mild scoliosis | Joint hypermobility | Small hands/feet | Stiff joints, small hands and feet, club foot |
| Gastrointestinal | — | — | G-tube | Inguinal hernia | Hiatal hernia, dysphagia, constipation | Umbilical hernia, imperforate anus |
| Genitourinary | — | — | Horseshoe kidney, micropenis, undescended testis | Unilateral renal agenesis, micropenis, small scrotum | Cryptorchidism | — |
| Skin | Capillary hemangiomas of nasal bridge and eyelids | Facial capillary hemangiomas | Sacral dimple, lipoma | ND | ND | Hemangiomas |
| Neurologic | Seizures | Seizures | Hypotonia | Hypotonia | Hypotonia/hypertonia, jerky movements, tethered cord | Seizures, tremor, hypotonia, incontinent |
| Other | Obstructive sleep apnea | Aggressive, quick tempered | Sleep disturbance | 2 vessel umbilical cord, obesity, gynecomastia | Sleep disturbance, incontinent | Impulsive, mood disorder, hypothyroidism, hypodontia |
| MRI | Enlarged 3rd ventricle, extra-axial fluid | Asymmetric ventricles | Decreased white matter, small corpus callosum, small brain stem | — | — | — |
ASD, atrial septal defect; G-tube, gastrostomy tube; HC, head circumference; IQ, intelligence quotient; MRI, magnetic resonance imaging; ND, no data; PDA, patent ductus arteriosus; yrs, years; (—) not present.