Table 1

Clinical features of three patients with de novo mutations in SCN8A

Patient123
Sex and ageFemale, 7 yearsMale, 33 yearsMale, 33 years
OFC (centile)51.5 cm (>P50)55.2 cm (P5–P10)55,8 cm (P10)
SeizuresFrequent, intractable seizures with an onset at the age of 6 weeksFirst seizures at age 18 months, including absences and tonic–clonic seizuresNone
DD/IDSevere DD since birth Not able to sit independently No speechModerate to severe DD
Walking at age 6 years
First words at age 6 years
Developmental level at adult age comparable to a 4–5 years old
DD since birth
Walking after 18 months
Relatively normal speech, but cannot write or read
Adult IQ of 55
Neurological symptomsNeonatal hypertonia
Severe dysregulation of muscle tone
Neurogenic bladder due to tethered cord
Nystagmus
Jerky pursuit
Spastic tetraplegia
None
Brain MRIProgressive cerebral atrophyCerebellar atrophyCerebral atrophy
DysmorphismsTapering fingers
Mild facial dysmorphisms, including synophrys, broad nasal tip and upslanted palpebral fissures
NonePtosis, asymmetric skull, broad forehead, high palate with narrow uvula, small jaw
Clinodactyly second fingers
Pectus excavatum
Miscellaneous
(non)-neurological
Precocious puberty
(6 years)
Convex scoliosis
Severe feeding difficulties
Unexplained spontaneous fractures
Decline in motor, and to a lesser extent in cognitive functioning since the age of 29 years Recurrent falls Swallowing difficultiesInguinal and umbilical hernia Behaviour problems Mild hypothyroidism
Mutations (de novo)SCN8A:
c.2952C>G
p.(Asn984Lys) near D2S6
SCN8A:
c.4351G>A
p.(Gly1451Ser) in D3S6
SCN8A: c.172G>A p.(Asp58Asn) in Nterm RING1: c.284G>A; p.(Arg95Gln)
  • Reference sequences SCN8A: NM_014191.2 and RING1: NM_002931.3. Mutation nomenclature is according to the Human Genome Variation Society guidelines.

  • DD, developmental delay; ID, intellectual disability; OCF, occipitofrontal circumference.