eTable 4. Recommended management of treatment in the 21 patients with a genetic diagnosis.

Patient	Phenotype (cardinal symptoms)	OMIM disease gene	Associated disease	Individually recommended measures
1	Severe global developmental delay, regression, dysmorphism	del 15q11q13	Angelman syndrome	Preventive (EEG monitoring initiated), symptomatic (speech therapy modified)
2	Severe global developmental delay, congenital cataract, microcephaly	COL4A1	BSVD	Preventive (ophthalmological monitoring modified, nephrological monitoring initiated)
3	Mild global developmental delay, dystonia, gait disorder	SGCE	DYT11	Curative (trihexyphenidyl), symptomatic (physiotherapy modified)
4	Moderate global developmental delay, short stature, facial dysmorphism	ANKRD11	KBG syndrome	None
5	Severe global developmental delay, short stature, dysmorphism	KAT6A	MRD32	Preventive (EEG, cardiological, ophthalmological, and orthopedic monitoring initiated), symptomatic (ergotherapy and speech ‧therapy modified)
6	Severe global developmental delay, spastic tetraplegic cerebral palsy, microcephaly	RNASEH2B	AGS2	Preventive (cardiological monitoring discontinued, ‧orthopedic and ophthalmological monitoring initiated), symptomatic ‧(physiotherapy ‧modified)
7	Severe global developmental delay, regression, movement disorder, myelinization disorder	RNASEH2C	AGS3	Preventive (neurological and ophthalmological monitoring ‧initiated), symptomatic (physiotherapy adjusted)
8	Moderate global developmental delay, ataxia, stereotypes	MYT1L	MRD39	None
9	Severe global developmental delay, leukodystrophy, cerebellar hypotrophy	TREX1	AGS1	None
10	Mild global developmental delay, regression, hypotonia	TH	Segawa syndrome	Curative (L-Dopa), preventive (EEG monitoring initiated), symptomatic (physiotherapy adjusted, ergotherapy initiated)
11	Severe global developmental delay, microcephaly, autism, stereotypes	MBD5	MRD1	Preventive (EEG monitoring initiated)
12	Mild global developmental delay, neurodegenerative disorder	FA2H	SPG35	Preventive (EEG-, urological, ophthalmological, and orthopedic monitoring initiated), symptomatic (physiotherapy modified, baclofen/Botox discussed)
13	Moderate global developmental delay, regression, neuropathy, pyloric stenosis	ARSA	MLD	Curative (inclusion in an MLD study), preventive (referral for specialist consultation)
14	Severe global developmental delay, severe encephalopathy, dystonia	GLE1	LCCS1, LAAHD	None
15	Severe global developmental delay, tapetoretinal degeneration, coordination disorder	RPIA	RPIA defiziency	Preventive (EEG monitoring initiated), symptomatic (physiotherapy modified)
16	Moderate delay in motor development, connective tissue weakness	IGHMBP2	DSMA1, CMT2S	Symptomatic (physiotherapy modified)
17	Severe global developmental delay, hypotonia, hearing and vision deficiencies	CHD2	EEOC	Preventive (EEG monitoring initiated)
18	Severe global developmental delay, microcephaly, muscular hypotonia	CHAMP1	MRD40	Symptomatic (speech therapy modified)
19	Moderate global developmental delay, short stature, deafness	del Xq28 (SSR4, PLXNB3, SRPK3, IDH3G)	CDG1Y	Preventive (coagulation and EEG monitoring, gastroenterological referral initiated), symptomatic (physiotherapy modified)
20	Severe global developmental delay, cardiac abnormalities, muscular hypotonia, facial dysmorphism	SON	ZTTK syndrome	Preventive (nephrological and dental monitoring, hearing test initiated; avoidance of radiography), symptomatic (speech therapy modified)
21	Severe global developmental delay, cardiac abnormalities, epilepsy, renal cyst	SON	ZTTK syndrome	Preventive (nephrological and dental monitoring, hearing test initiated; avoidance of radiography), symptomatic (ergotherapy adjusted, speech therapy initiated)

AGS2, Aicardi–Goutières syndrome 2; AGS3, Aicardi–Goutières syndrome 3; BSVD, brain small vessel disease with or without ocular anomalies; CDG1Y, congenital disorder of glycosylation type 1y; CMT2S, Charcot–Marie–Tooth disease, axonal, type 2S; DSMA1, spinal muscular atrophy, distal, autosomal recessive 1; DYT11, dystonia 11; EEOC, epileptic encephalopathy childhood onset; KBG syndrome, designation composed of the initials of the surnames of the first three patients described; LAAHD, lethal arthrogryposis with anterior horn cell disease; LCCS1, lethal congenital contracture syndrome 1; MLD, metachromatic leukodystrophy; MRD1, mental retardation, autosomal dominant 1; MRD32, mental retardation, autosomal dominant 32; MRD39, mental retardation, autosomal dominant 39; MRD40, mental retardation, autosomal dominant 40; OMIM, Online Mendelian Inheritance in Man; SPG35, spastic paraplegia, autosomal recessive 35; ZTTK syndrome, Zhu–Tokita–Takenouchi–Kim syndrome