Table 4 Summary of clinical features of patients with variation/aberration within the SETD1B gene
From: A genome-wide DNA methylation signature for SETD1B-related syndrome
Specific SETD1B-related DNAm signature (this study) | Other previously reported patients (not included in this study) | Non-SETD1B DNAm signature | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Clinical features | mut_1 Male 13 years Disrupted SETD1B | mut_2 Male 16 years Disrupted SETD1B | 3_mut Male 34 years Disrupted SETD1B | 4_mut Female 12 years Disrupted SETD1B | 5_mut Male 7 years Disrupted SETD1B | 2_del12q Female 12 years Disrupted SETD1B and KDM2B | 3_del12q Male 3 years Disrupted SETD1B and KDM2B | 4_del12q Female 16 years Disrupted SETD1B | Baple et al. [1] Female 11 years Disrupted SETD1B and KDM2B | Palumbo et al. [3] Female 11 years Disrupted SETD1B and KDM2B | 6_mut Male 8 years VUS SETD1B | 7_mut Male 10 years VUS SETD1B |
Growth parameters at birth | ||||||||||||
Height | 48 cm | NA | NA | – | 47 cm (5th centile) | 52 cm (+ 0.45 SD) | NA | NA | NA | NA | NA | NA |
Weight | 2.9 kg | 2.52 kg (2.5 SD) | 3.6 kg (+ 1.5 SD) | 3.55 kg (+ 1.4 SD) 34.5 cm (+ 1.1 SD) | 2.8 kg (9th centile) | 3.78 kg (+ 1.45 SD) | NA | NA | 4094 g (90–95th centile) | 2650 g (5–10th centile) | 3260.2 (25–50th centile) | NA |
Head circumference | 33 cm | NA | NA | NA | 33 cm (10th centile) | 35 cm (− 0.1 SD) | NA | NA | NA | NA | NA | NA |
Growth parameters at last evaluation | ||||||||||||
Height | 167.5 cm (at 30 years) | 193 cm (+ 1.45SD) | NA | NA | 1.35 m (+ 1.8 SD) | 170 cm (+ 1.2SD) (at 13) | NA | (98th centile) | 157.5 cm (98th centile) | (10–25th centile) | 13 cm (67th centile) | NA |
Weight | 111.8 kg (at 30 years) | 67 kg (− 0.15SD) | NA | NA | 46 kg (>> + 3 SD) | 84.9 kg; + 2.5 SD (according to height) | NA | (98th centile) | 91.5 kg (98–99,6th centile) | (10–25th centile) | 46.8 kg (95th centile) | |
Head circumference | 60 cm (at 30 years) | NA | NA | NA | 51 cm (− 1.2 SD) | 48 cm; − 0.97 SD at 3 years | NA | (98th centile) | 54.8 cm (75th centile) | (10–25th centile) | 54 cm | NA |
Dysmorphisms | ||||||||||||
Head | – | NA | NA | Normal | NA | Prominent forehead | Narrow face, prominent forehead, plagiocephaly | NA | NA | NA | Very fair hair | NA |
Eye | – | Up slant palpebral fissures, proptosis | Thick eye brows | Normal | Thick eyebrows, hypertelorism, sunken eyes, short palpebral fissures | Telecanthu, epicanthus | Hypertelorism | Up slanting palpebral fissures, synophrys | NA | NA | Very Fair (blue) | Upslant palpebral fissures, myopia |
Ear | – | Normal | Normal | Normal | Thick helix | Tags preauriculair | Folded ear ridges | Small, low set and posteriorly rotated | Large, narrow with thick helix and rotated | Large and narrow with a thick helix | NA | NA |
Nose | – | Asymmetric due to cleft lip | Normal | Normal | Normal | Short upturned nose, large nose bridge | NA | Height nasal bridge, square tip | Broad nasal based | Broad base; high root | NA | NA |
Cheeks | Full | Normal | Full | Normal | Full | Full | NA | NA | Full | Full | NA | NA |
Lip | – | Cleft lip | Full lower lip | Normal | Full | Full lower lip; short philtrum | NA | NA | Full and everted lower lip | Full and everted lower lip | NA | Malformation of upper lip, prominent upper lip |
Mouth | – | Cleft jaw bilateral | NA | Normal | NA | Macroglossia; prognathic | NA | Minor micrognathia | Macroglossia | Macroglossia | NA | NA |
Palate | – | Cleft palate | NA | Normal | NA | NA | NA | Narrow palate | High arch | High arch | NA | NA |
Teeth | – | Misaligned due to cleft jaw | NA | Normal | Oligodontia | Irregular, oligodontia | NA | Prominent front incisors | Overcrowded | Overcrowded | NA | Malaligned teeth with increased spacing |
Developmental delay | ||||||||||||
Intellectual disability | Mild – moderate | Mild | Profound | Mild | Profound | + | Moderate | Moderate | moderate to severe | mild-to-moderate | + | |
Motor development | Walk without support | – | Walk without support | Walk without support | Walk without support | Normally but her movements are not fluent | + | Global developmental delay | Walk with a broad-based gait | global developmental delay | global developmental delay | + |
Language delay | + | + | + | + | + | + | + | – | +; few words at 2 years old | – | first words at 3 years | NA |
Anxiety | – | – | + | – | + | – | + | + | – | NA | ||
Autism/autistic behavior | – | – | + | + | + | + | + | – | +; at 4 years | + | – | + |
Epilepsy/seizures/spasms | ||||||||||||
Type | Frontal-temporal | In early childhood absences, alter tonic-clonic seizures | Myoclonic seizures (3y11m) | Myoclonic seizures (2y9m), | NA | NA | Myoclonic seizures | NA | – | Tonic-clonic seizures | No seizures | Tonic-clonic seizures remotely in childhood and more recently complex partial seizures |
Fingers abnormality | NA | Fetal pads | Tapering fingers- mild | – | Tapering fingers-mild | Clinodactyly | Tapering fingers | Tapering fingers with prominent fingertip pads | Tapering finger – mild left 4th finger proximally implanted | Tapering fingers – mild | – | Long fingers, widened tips, 5th finger clinodactyly |
Toes | Foot pronation | Normal | NA | NA | NA | NA | NA | Bilateral hypo-plastic nails on both halluces | Short toes | NA | – | NA |
Hypoglycemia | – | – | – | – | NA | – | NA | NA | + | + | – | NA |
Hypotonia | + | – | – | – | NA | – | + | – | + | – | – | NA |
Additional findings | Obsessive interest for electronic objects and their accumulation, acute pancreatitis, cholecystectomy, liver steatosis | Urinary continence problems | Umbilical hernia at birth, hyperactivity - PDD NOS/ADHD; obstipation | T cell skin lymphoma on the lower back; hypo-plastic nails, patchy eczema, thick ichthyic skin | Cafe-au-lait spot:1 truncal; large hands and feet; urinary continence problems inverted nipples; | His skin is also very fair | Cerebral visual impairment; ptosis | |||||