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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

From: Diagnosis and management of individuals with Fetal Valproate Spectrum Disorder; a consensus statement from the European Reference Network for Congenital Malformations and Intellectual Disability

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
    Score
Supportive Congenital cardiac defect Confirmed on echo 2
Suggestive Cleft palate   2
Supportive Metopic suture synostosis   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   2
Supportive Joint laxity Beighton 6 or more 1
Supportive Talipes requiring surgery   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