Table 1. Phenotype of the patients with a PUF60 variant and the patients with a 8q24.3 deletion comprising PUF60.
| Patients with a PUF60 variant | Patients with a 8q24.3 deletion | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P1 | P2 | P3 | P4 | P5 | Dauber et al,8 P6 | Verheij et al,6 P1 | Dauber et al,8 P1 | Dauber et al,8 P2 | Dauber et al,8 P3 | Dauber et al,8 P4 | Dauber et al,8 P5 | Wells et al,7 P1 | |
| Gender | F | M | M | M | F | F | M | F | M | F | F | F | F |
| Age | 3 y | 14 y | 7 y | 17 y | 12 y 2 m | 21 y | 4 m | 10 y | 6 y | 17 y | 9 y | 11 y | 28+6 WG |
| Facial features | |||||||||||||
| Square face | + | + | − | + | + | + | + | + | + | + | + | + | + |
| Full cheeks | + | − | + | + | + | − | + | + | + | + | + | + | − |
| Bitemporal narrowing | + | − | + | + | − | ND | + | ND | ND | + | + | + | + |
| Prominent forehead | + | + | + | + | + | + | + | + | + | − | + | + | − |
| Low set eyebrows | + | + | + | + | + | + | + | − | + | − | + | + | + |
| Wide nasal bridge | + | + | − | + | + | − | + | ND | + | − | + | + | + |
| Broad nasal tip | + | + | + | + | + | + | + | + | + | + | + | + | + |
| Anteverted nares | + | + | + | + | − | + | + | + | + | + | + | + | + |
| Long philtrum | + | + | + | + | + | + | + | + | + | + | + | + | + |
| Thin upper lip | + | − | + | + | + | + | + | + | + | + | + | + | + |
| Micro- or retrognathism | + | − | − | + | − | + | + | + | − | − | − | + | + |
| Short neck | + | − | − | + | + | + | + | − | + | + | + | + | + |
| Branchial arch anomalies | Branchial cleft cysts | − | − | Branchial cleft cysts, uvula dimple | − | − | Branchial arch remnant, fistula | Bilateral preauricular pits | − | − | Bilateral preauricular pits | − | − |
| Eye anomalies | |||||||||||||
| Coloboma | + (IRC) | − | − | − | − | − | + (IRC) | + (IC) | + (IRC) | − | − | − | − |
| Other | Bilateral microphtalmia and optic nerve hypoplasia | Strabismus | − | −a | Bilateral optic nerve hypoplasia | − | Hyperopia | ||||||
| Cardiac defects | |||||||||||||
| VSD | + | − | + | − | − | + | + | − | − | + | − | + | − |
| Other | − | − | Truncus arteriosus | Aortic insufficiency | AVSD | Bicuspid aortic valve | − | − | − | Truncus arteriosus | Aortic coarctation | AVSD, hypoplastic aortic arch | |
| Laryngo-tracheo-broncomalacia | − | − | + | − | − | − | + | − | − | − | − | + | − |
| Growth | |||||||||||||
| IUGR | + | − | + | − | − | + | + | + | − | + | + | − | + |
| Short stature | + | − | + | + | + | + | + | + | + | + | + | + | NA |
| Micromelia | + | − | + | − | − | + (asymmetric) | ND | ND | ND | ND | ND | ND | + |
| Microcephaly | − | − | + | − | − | + | + | + | + | − | − | + | − |
| Skeletal anomalies | |||||||||||||
| Joint laxity/dislocation | +b | − | + | + | + | +b | +b | − | + | +c | + | +b | − |
| Distal limb anomalies | + a, b | + a | − | + b, f, i | j, k | + c | + d, e | − | − | − | + | + a, h | + a, f, g |
| Vertebral anomalies | − | − | Fusion of the left facet joints of C5−C6 | Unfused arch of C7, scoliosis | − | Hemivertebrae, scoliosis | − | + | − | Fusion of L5-S1 | − | Hemivertebrae, scoliosis | Mild scoliosis, abnormal third sacral vertebra |
| Feeding difficulties | + | − | + | − | + | − | + | − | − | + | + | + | NA |
| Neurology | |||||||||||||
| Developmental delay | + | + | + | + | + | + | + | − | + | + | + | + | NA |
| Seizures | − | − | − | −d | − | + | + | − | − | − | − | + | − |
| Brain malformation | Posterior pituitary ectopia | ND | − | ND | CC hypoplasia | Enlarged 3rd and lateral ventricles, thin CC | Hypoplastic CC, cerebral atrophy, enlarged ventricles | − | Cerebral atrophy | − | Ischemic encephalomalacia | Volume loss in the left temporal lobe | − |
| Renal anomalies | − | − | − | Hypoplastic kidneys | Pelvic left kidney with unilateral VUR | − | − | Left renal agenesis | − | Left polycystic kidney | Ectopic fused kidneys | Right kidney hypoplasia with renal cyst | − |
| Other | Naevus flammeus on the forehead and eyelids, pectus excavatum | Autistic features | Autistic features, pectus excavatum, scoliosis | Trilobar left lung | Cleft palate, BPD, pes planus, hemifacial microsomia | Coarse hair, CHL | Recurrent infections, hiatus hernia | − | Forehead capillary hemangioma | Cyclic vomiting | Small medial alveolar cleft | ||
| De novo PUF60 variants (NG_033879.1; NM_078480.2) | c.24+1G>C chr8:g. 144911449C>G | c.1342C>T p.(Arg448*) | c.1448T>C p.(Val483Ala) | c.407_410delTCTA p.(Ile136Thrfs*31) | c.901A>T p.(Lys301*) | c.505C>T p.(His169Tyr) | Deletion | Deletion | Deletion | Deletion | Deletion | Deletion | Deletion |
Abbreviations: AVSD, atrioventricular septal defect; BPD, bronchopulmonary dysplasia; CC, corpus callosum; CHL, conductive hearing loss due to middle ear malformation; IC, iris coloboma; IRC, irido–retinal coloboma, IUGR, intrauterine growth retardation; NA, not applicable; ND, not determined, VSD, ventricular septal defect; VUR, vesicoureteral reflux; WG, weeks of gestation.
Distal limb anomalies: a: clinodactyly of the fifth digit; b: valgus deformity of the feet; c: absent right thumb, hypoplastic metacarpal and scaphoid bones; d: bilateral post-axial polydactyly; e: oligodactyly and fusion of the third and fourth metatarsal of the left foot; f: brachymesophalangy of the fifth digit; g: rocker-bottom feet; h: Bilateral transverse palmar creases; i: overlying proximal thumb; j: brachydactyly, k: flat feet with short halluces and sandal gap deformity.
No focused ophthalmological examinations have been performed since the age of 3 years.
Hip dislocation.
Elbow subluxation with malformation of the great sigmoid cavity.
EEG showed epileptiform discharges with absence of seizures.