Table 1.
Clinical scoring system for the phenotypic features in POGZ-patients.
| 1. DYSMORPHIC FACIAL FEATURES | CLINICAL SCORES |
|---|---|
| Broad/high forehead/bitemporal narrowing | Scoring from 1 to 4 (mild-to-severe facial dysmorphism)
|
| Hypertelorism | |
| Downslanting or upslanting palpebral fissures | |
| Epicanthus | |
| Ptosis | |
| High-arched/sparse eyebrows | |
| Broad nasal tip | |
| Depressed, flat nasal bridge | |
| Pear-shaped nose | |
| Midface hypoplasia/retrusion | |
| Short philtrum | |
| Downturned corners of mouth (triangular/tented) | |
| Upper lip (cupid’s bow) | |
| Thin vermillion/thin upper lip | |
| Everted upper/lower lip | |
| Open mouth | |
| Macrostomia | |
| Protrusion of the tongue/macroglossia | |
| High-arched palate | |
| Bifid uvula | |
| Mandibula (prognathia or micro-retrognathia) | |
| Pointed chin | |
| Low-set ears | |
| Posteriorly rotated ears | |
| Over-folded/abnormally folded helices | |
| 2. ABNORMALITY OF THE EYE | |
| Strabismus | 1 scoring point/symptom |
| Myopia | |
| Hypermetropia | |
| Anisometropia | |
| Astigmatism | |
| Iris coloboma | |
| Optic nerve atrophy or hypoplasia | |
| Rod-cone dystrophy | |
| Cortical visual impairment | |
| Abnormal electroretinogram | |
| Abnormal visual evoked potentials | |
| 3. ABNORMALITY OF THE NERVOUS SYSTEM | |
| Global developmental delay |
Developmental delay and intellectual disability were scored from score 1 (+, mild) to score 4 (++++, severe) based on the MEAN of the scoring points given for gross motor (A), speech delay (B) and IQ-level (C) (Details seen in Supplementary Table S1):
|
| Gross motor developmental delay | |
| Age at walking | |
| Fine motor developmental delay | |
| Speech delay/No speech | |
| Age at talking | |
| Receptive language disorder | |
| Expressive language disorder | |
| Intellectual disability (IQ, if applicable) | |
| Aplasia/hypoplasia of the corpus callosum | Additional scores:
No score for antiepileptics |
| Cerebral atrophy | |
| Polymicrogyria/simplified gyral pattern | |
| Brainstem hypoplasia | |
| Cerebellar dysplasia/hypoplasia | |
| Periventricular white matter lesion | |
| Delayed myelination | |
| Optic chiasma dysplasia | |
| Dandy-Walker malformation/variant | |
| Ventriculomegaly | |
| Other central nervous system (CNS) abnormality | |
| Sensorineural hearing loss (bilateral/unilateral) | |
| Seizures | |
| EEG abnormality | |
| Hypoglycemic seizures | |
| Febrile seizures | |
| Antiepileptics (mono therapy/combined) | |
| 4. BEHAVIORAL ABNORMALITIES | |
| Autism spectrum disorder | 1 scoring point/behavioral abnormality |
| (Self-)injurious behavior | |
| Anxiety | |
| Attention deficit hyperactivity disorder | |
| Limited social interactions | |
| Low frustration tolerance (tantrums) | |
| 5. ABNORMALITY OF THE MUSCULATURE | |
| Hypotonia (facial, axial, appendicular, generalized, others) |
0 scoring point: no hypotonia/not reported 1 scoring point: if any type of hypotonia was reported |
| 6. NORMALITY OF THE CARDIOVASCULAR SYSTEM | |
| Congenital heart defect | 1 scoring point/cardiovascular defect |
| Atrial septal defect | |
| Persistent ductus arteriosus | |
| 7. ABNORMALITY OF THE SKELETAL SYSTEM | |
| Brachycephaly | 1 scoring point/skeletal abnormality |
| Microcephaly | |
| Plagiocephaly | |
| Head circumference in cm (percentile/-SD) | |
| Cleft palate | |
| Short neck | |
| Brachydactyly/Small hands | |
| Syndactyly | |
| Broad fingers and toes | |
| Clinodactyly | |
| Joint laxity | |
| Scoliosis | |
| Contractures | |
| Short stature | |
| Skeletal anomalies of the lower extremities | |
| 8. ABNORMALITY OF THE DIGESTIVE SYSTEM | |
| Feeding difficulties: dysphagia, swallowing difficulty | 1 scoring point/gastrointestinal abnormality |
| Tube feeding/Gastrostomy tube | |
| Gastroesophageal reflux | |
| Constipation | |
| Cyclic vomiting | |
| Failure to thrive | |
| Overweight/Obesity | |
| Diaphragmatic hernia | |
| Other hernias | |
| Intestinal malrotation, intussusception | |
| Rectal prolapse | |
| 9. PERINATAL MEDICAL HISTORY | |
| Prenatal or postnatal complications and findings (high nuchal translucency, low Apgar scores, microcephaly, etc.) |
0 scoring point: no prenatal/perinatal problem or not reported 1 scoring point: if any type of problem was reported |
| 10. GENITO-URINARY TRACT ABNORMALITY | |
| Duplicated renal collecting system | 1 scoring point/genito-urinary abnormality |
| Ureteropelvic junction obstruction | |
| Renal dysplasia | |
| Cryptorchidism | |
| Hypoplastic scrotum | |
| Hypoplastic testes | |
| Micropenis | |
| Phimosis | |
| Primary amenorrhea | |
| 11. MISCELLANEOUS | |
| Sleep disturbance (obstructive sleep apnea) | 1 scoring point/abnormality |
| Frequent respiratory infections | |
| Recurrent otitis media | |
| Others | |
| CUMULATIVE CLINICAL SCORE: | SUM of the scores given to organ system/category 1–11 |
The detailed clinical scoring for each patient is presented in Supplementary Table S1. In the section of nervous system abnormalities + indicates the severity in the Supplementary Table S1: +: 1 scoring point, ++: 2 scoring points, +++: 3 scoring points, ++++: 4 scoring points. In patients with less clinical details, dysmorphic features were not evaluated for the clinical score due to the lack of clinical information or photos of patients.