Patient | 1 | 2 | 3 |
---|---|---|---|
Sex and age | Female, 7 years | Male, 33 years | Male, 33 years |
OFC (centile) | 51.5 cm (>P50) | 55.2 cm (P5–P10) | 55,8 cm (P10) |
Seizures | Frequent, intractable seizures with an onset at the age of 6 weeks | First seizures at age 18 months, including absences and tonic–clonic seizures | None |
DD/ID | Severe DD since birth Not able to sit independently No speech | Moderate 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 symptoms | Neonatal hypertonia Severe dysregulation of muscle tone Neurogenic bladder due to tethered cord | Nystagmus Jerky pursuit Spastic tetraplegia | None |
Brain MRI | Progressive cerebral atrophy | Cerebellar atrophy | Cerebral atrophy |
Dysmorphisms | Tapering fingers Mild facial dysmorphisms, including synophrys, broad nasal tip and upslanted palpebral fissures | None | Ptosis, 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 difficulties | Inguinal 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.