Table 1.
Clinical, Radiological, and Biochemical Features of Individuals with Biallelic UBE3B Mutations
|
Family 1 |
Family 2 |
Family 3 |
||
|---|---|---|---|---|
| Individual 1 | Individual 2 | Individual 3 | Individual 4 | |
| Origin | Israel | Italy | Tunisia | |
| Parental consanguinity | + (first cousins) | - | - | + (first cousins) |
| Sex | F | F | M | F |
| Pregnancy/Neonatal Period | ||||
| Oligohydramnios | - | - | + | - |
| Respiratory problems | stridor due to laryngomalacia | apnea | - | stridor due to laryngomalacia |
| Feeding difficulties/GER | + | (+) (improved at 5 years) | + | + |
| Frequent infections | recurrent otitis media | - | recurrent bronchitis until 1 year | recurrent respiratory infections |
| Growth | ||||
| Failure to thrive | + | + | + | + |
| Short stature | - | + | + | + |
| Microcephaly | + | + | + | + |
| Motor and Cognitive Development | ||||
| Delayed motor milestones | + | + | + | + |
| Absent speech | + (3 years 3 months) | + (7 years 7 months) | + (3 years 1 month) | + (17 months) |
| Severe intellectual disability | + | + | + | severe developmental delay |
| Craniofacial | ||||
| Blepharophimosis | + | + | + | + |
| Ptosis | + | + (left) | - | + |
| Upward-slanting palpebral fissures | - | + | + | - |
| Telecanthus | + | + | + | + |
| Hypertelorism | - | + | + | + |
| Depressed nasal bridge | + | + | + | + |
| Anteverted nares | + | + | + | + |
| Low-set/dysplastic ears | + | + | + | + |
| Palatal anomalies | high arched palate | + (submucous cleft palate) | - | - |
| Micrognathia | + | + | + | + |
| Small mouth | + | + | + | + |
| Neurological | ||||
| Abnormal brain image | chiari type I malformation, ventricular dilatation, hypoplastic CC | agenesis of the CC rostrum, anterior commissure not evident | reduced size of the pituitary gland, partial empty sella | hypoplastic CC |
| Axial hypotonia | + | + | - | + |
| Ocular impairment | + (astigmatism) | + (astigmatism, mild strabism, and myopia) | - | - |
| Hearing impairment | + (conductive) | - | - | - |
| Ectodermal Anomalies | ||||
| Sparse thin hair/eyebrows | + | + | + | + |
| Eczema | - | - | + | - |
| Thin skin | + | + | + | + |
| Cardiac | ||||
| Congenital heart disease | + (ASD, VSD, aortic coarctation) | - | - | + (ASD) |
| Gastrointestinal | ||||
| Gastrectasia | - | + | - | - |
| Constipation | - | (+) (resolved at 6y) | + | - |
| Distension of gall-bladder | - | + | - | - |
| Intestinal malrotation | + | - | - | - |
| Skeletal/Limb | ||||
| Clinodactyly of 5th fingers | - | + | + | - |
| Congenital dislocation of the hip | + | - | - | + |
| Urogenital abnormalities | mild left pyelectasis | double right kidney, right pyelectasis | - | Hypoplastic labia majora |
| Endocrine and Laboratory Anomalies | ||||
| Thyroid anomalies | - | elevated TSH (until 5 years) and reduced thyroid gland volume | - | - |
| Low growth hormone levels | NA | - | + | NA |
| Low ACTH level | NA | - | + | NA |
| Anomalies of cholesterol levels | low HDL cholesterol | low total cholesterol | - | low total cholesterol |
| Others | severe hyperlaxity | torticollis, delayed bone age | - | partial epilepsy |
| UBE3B mutation paternal allele | c.1741+2G>C | c.545−2A>G | c.545−2A>G | c.2180A>C (p.Gln727Pro) |
| UBE3B mutation maternal allele | c.1741+2G>C | c.2223_2224delAG (p.Arg741Serfs∗3) | c.2223_2224delAG (p.Arg741Serfs∗3) | c.2180A>C (p.Gln727Pro) |
Abbreviations: ASD, atrial septal defect; CC, corpus callosum; GER, gastresophageal reflux; HDL, high-density lipoprotein; NA, not available/not performed; VSD, ventricular septal defect.