Table 4 Diagnostic Criteria For Fetal Valproate Spectrum Disorder. For diagnostic criteria to be met all essential criteria must be fulfilled in addition to two suggestive criteria or one suggestive plus a supportive score of 3 or more
Grade | Criterion | Comments | |
|---|---|---|---|
Essential | Confirmed exposure to VPA during pregnancy | Any dose or duration | |
Essential | Has no other recognisable diagnosis which would explain the phenotype | As evidenced on assessment by a clinical geneticist or other professional with relevant expertise | |
Essential | Normal microarray-CGH and Fragile X studies | Part of diagnostic work-up | |
Essential | Other teratogenic disorders with clinical overlap excluded | In particular fetal alcohol syndrome / spectrum disorder | |
Suggestive | Facial dysmorphism consistent with VPA exposure (flat philtrum, thin upper lip, full, everted lower lip, short anteverted nose, small mouth, epicanthic folds, neat arched eyebrows, broad nasal root) see Fig. 3 | Include review of photographs at a younger age and take into account variability of phenotype with age (see Fig. 3) | |
Suggestive | Cognitive profile consistent with current knowledge of that associated with valproate exposure | a) discordant from parents b) in infancy: motor and speech delay, c) school aged: IQ, verbal reasoning, communication and executive functioning deficits | |
Suggestive | Presence of social communication difficulties/autism spectrum disorder | Occurs in 6–15% | |
Suggestive | Spina bifida | 20 fold risk | |
| Â | Â | Â | Score |
Supportive | Congenital cardiac defect | Confirmed on echo | 2 |
Suggestive | Cleft palate | Â | 2 |
Supportive | Metopic suture synostosis | Â | 2 |
Supportive | Radial ray defect | Includes mild variants with flat thenar eminences | 2 |
Supportive | Genitourinary malformations | Hypospadias, abnormal collecting system, hydronephrosis | 2 |
Supportive | Laryngomalacia/stridor | Â | 2 |
Supportive | Joint laxity | Beighton 6 or more | 1 |
Supportive | Talipes requiring surgery | Â | 1 |
Supportive | Digital anomalies | Overlapping toes, camptodactyly, clinodactyly | 1 |
Supportive | Ophthalmological anomalies | Coloboma, strabismus, refractive error | 1 |
Supportive | Enuresis/poor bladder control | Requiring investigation | 1 |