Child with predominant midline stereotypies and infrequent seizures.

Description

A 4-year-old boy, sixth born of third-degree consanguineous marriage, presented with a brief unprovoked generalised seizure at 1.5 years of age. Following this, he developed progressive ataxia, vision loss, autistic features with poor eye contact, midline motor stereotypies and cognitive decline. He had unremarkable perinatal and family history. Examination revealed microcephaly, bilateral optic atrophy and ataxia. Electroencephalography (EEG) revealed generalised delta–theta slowing with a paucity of sleep markers (figure 1). Photic stimulation was unremarkable. MRI of the brain revealed diffuse atrophy (cerebellar>>cerebral) (figure 2). A visual evoked potential showed no clear waveforms on either side. Clinical exome sequencing revealed a novel homozygous c.1078C>T (p.Q360*) pathogenic stop gain variant in exon 11 of the MFSD8 gene. This mutation was likely pathogenic and was confirmed by Sanger sequencing. At 6 years of age, the child had no further seizures with midline motor stereotypies, microcephaly, breathing difficulties, insomnia and in a bed-bound state.

Figure 1

Sleep electroencephalographic 10 s epoch (average montage; sensitivity: 10 μV/mm; sweep: 30 mm/s) showing generalised delta–theta slowing along with paucity of sleep markers.

Figure 2

Fluid-attenuated inversion recovery (A) and T1 (B) weighted images of MRI of the brain showing peritrigonal white matter hyperintensities (small arrows) along with diffuse atrophy (cerebellar>>cerebral) (large arrows).

The neuronal ceroid lipofuscinosis (NCLs), previously referred to as Batten’s disease, is a group of most common autosomal recessive lysosomal storage disorders. They have a common symptom complex of neuroregression, epilepsy and various ophthalmological abnormalities.1 MFSD8-related NCL-7 typically begins between 2 and 11 years of age. The initial features usually include infrequent seizures, neuroregression and occasionally stereotypical hand movements.1 2 The characteristic early photosensitivity described for CLN-2 disease may not be often seen.3 4 The other classical EEG findings described in NCL are abundant posterior lead discharges and generalised background slowing. The novel features seen in our case were infrequent seizures, presence of predominant midline stereotypies, lack of abundant posterior discharges and photosensitivity.4 Hence, it is important to consider the possibility of NCL in a child with infrequent seizures and midline stereotypies. Genetic diagnosis and counselling play a crucial role in the management of these children.

To conclude, NCL-7 can present with global development delay, midline stereotypies, seizures which are well controlled with anti-seizure drugs with and without autistic features.

Neuronal ceroid lipofuscinosis (NCL) usually presents with refractory epilepsy, neuroregression and various ophthalmological abnormalities.

However, NCL-7 can present with infrequent seizures and midline stereotypies.