Table 1.
Phenotypic Manifestations of Weaver Syndrome in Patients with EZH2 Mutations
| Phenotypic Manifestation | Proband 1 c.457_459del (p.Tyr153del) | Proband 2 c.2080C>T (p.His694Tyr) | Proband 3 c.394C>T (p.Pro132Ser) |
|---|---|---|---|
| Gestational age at delivery (weeks) | ∼36.5 | 32 | 42 |
| Birth weight (kg) | 4.82 | 3.26 | 4.50 |
| Birth length (cm) | 55.0 | 50.8 | 55 |
| Birth head circumference (cm) | 36.5 | ∼34 | Nk |
| Recent weight (kg) [age measured] | 118 [30 years] | 64.1 [10 years, 11 months] | 103.3 [19 years, 9 months] |
| Recent height (cm) [age measured] | 190.5 [30 years] | 179 [10 years, 11 months] | 177.7 [19 years, 9 months] |
| Excessive growth of prenatal onset | +++ | +++ | +++ |
| Accelerated osseous maturation | ++++ | ++++ | ++++ |
| Neurological Features | |||
| Hypertonia | ++ | – | – |
| Hypotonia | – | ++ | ++ |
| Hoarse, low-pitched cry | ++ | ++ | ++ |
| Intellectual disability | mild | borderline-mild | mild |
| Excessive appetite | ++ | ++ | – |
| Ventriculomegaly | ++ | Nk | – |
| Delayed myelination | Nk | Nk | + |
| Cerebellar hypoplasia (mild) | – | Nk | + |
| Seizures (age of onset) | tonic-clonic [13 years] | – | brief absence [15 years] |
| Poor fine motor coordination | ++ | + | ++ |
| Poor balance and gravitational insecurity | ++ | ++ | ++ |
| Fatty filum terminale | – | – | ++ |
| Craniofacial | |||
| Macrocephaly | +++ | +++ | +++ |
| Large bifrontal diameter | +++ | +++ | +++ |
| Flat occiput | + | – | + |
| Large ears | +++ | + | + |
| Ocular hypertelorism | ++ | ++ | – |
| Downslanted palpebral fissures | + | + | + |
| Long philtrum | ++ | ++ | ++ |
| Retrognathia | + | + | + |
| Cardiovascular | |||
| Patent ductus arteriosus | – | – | + |
| Hands | |||
| Prominent digit pads | ++ | ++ | ++ |
| Single transverse palmar crease | – | – | – |
| Camptodactyly | ++ | + | – |
| Broad thumbs | ++ | ++ | – |
| Thin, deep-set nails | ++ | ++ | ++ |
| Feet | |||
| Clinodactyly, toes | + | + | – |
| Talipes equinovarus | ++ | – | – |
| Short fourth metatarsals | + | – | – |
| Hind foot valgus | – | – | + |
| Limited elbow and knee extension in early life | + | – | + |
| Limited elbow and knee extension after puberty | + | – | + |
| Widened distal femurs and ulnas | ++ | Nk | – |
| Skin | |||
| Excessive loose skin | ++ | ++ | – |
| Inverted nipples | + | – | – |
| Thin hair | + | – | – |
| Increased pigmented nevi | – | ++ | ++ |
| Connective Tissue | |||
| Umbilical hernia | ++ | + | + |
| Inguinal hernia | ++ | – | – |
| Scoliosis (degrees) | 20 | 10 | 16 |
| Endocrine | |||
| Hypothyroidism [age of onset] | ∼25 years | – | – |
| Growth hormone deficiency [age of onset] | ∼27 years | – | – |
Key: + = minimally present, ++ = obviously present, +++ = very prominent, ++++ = severe, – = assessed and found to be absent, Nk = not known.