Van der Knaap Disease: A Case Series Highlighting Clinical and Radiological Features

Megalencephalic Leukoencephalopathy (MLC) presents with enlarged head circumference, delays in developmental milestones, and recurrent seizures. The present case series, was conducted over ten years, and assessed by Magnetic Resonance Imaging (MRI) and clinical features in familial and non-familial cases of van der Knaap disease. Twelve patients were evaluated, of whom five were familial and seven non-familial, 8 males and 4 females. Macrocephaly was invariably present along with delays in gross motor milestones in six of the 12 cases (50%), and a seizure disorder was present in eight of the 12 cases (66.7%). Of the eight patients with seizures, 7 (87.5%) had generalised tonic-clonic seizures, while simple partial seizures was observed in only 1 (12.5%) case. Motor and intellectual impairment were more severe in patients with extra-temporal lobar subcortical cysts, present in seven of the 12 (58.3%) cases. The classical MRI features include diffuse white matter involvement (T2/FLAIR hyperintensity) with subcortical cysts in the anterior temporal region (rarely in the frontoparietal region), sparing of deeper structures, and varying degrees of cerebral atrophy; diffuse white matter involvement and anterior temporal subcortical cysts were observed in 100% of our cases. Early MRI should be considered for asymptomatic siblings of an affected family to enable early diagnosis and treatment initiation. Clinicians should maintain a high index of suspicion for van der Knaap disease; when clinically suspected, MRI of the brain should be performed for diagnosis. Screening of other family members should also be advised to detect asymptomatic cases. Because the MRI features are highly suggestive of van der Knaap disease, further investigations such as genetic testing may be avoided. As it is an autosomal recessive disorder, patients and their relatives should be counseled to prevent consanguineous marriages and thereby reduce transmission of the disease.