A 14-month-old baby boy, only child of a third degree consanguineous marriage presented to us with an upper respiratory infection and an episode of simple febrile seizure. There were no episodes of convulsions in the past or in the family. During the antenatal period, only a single screening ultrasonography (USG) at 9th month of pregnancy was done, which was suggestive of fetal hydrocephalus. It was a term elective cesarean section delivery with apparently no neonatal problems. Birth weight was 2,200 g, head circumference was 30 cm, and birth length was 45 cm. The family had migrated from Bangladesh and no other significant history was elicitable. Developmentally there was a gross delay in all the milestones. On examination, baby was failing to thrive with the weight being 6 kg and length being 65 cm. The head circumference was 35 cm (<3rd centile). Bilateral esotropia with right eye microphthalmia was present. Fundus examination of both the eyes was abnormal. Pupils were unequal and nonreactive. Generalized hypotonia with depressed reflexes and bilateral equivocal plantars were present. Power in all the limbs was 3/5. There was no muscle hypertrophy or wasting. Other systemic examination findings were within normal limits.
A detailed ophthalmic examination showed high myopia of the left eye with posterior synechiae, vitreous floaters, peripheral vasculitis, and severe choroidal exudates [Figure 1]. The fundus examination of the right eye was not possible due to posterior synechiae.
Figure 1.
Fundus of the left eye showing peripheral vasculitis and severe choroidal exudates (white arrow)
Serum creatine phosphokinase (CPK) was elevated at 1,463 U/l. Motor nerve conduction studies showed low amplitude of motor response with mild sensory neuropathy in lower limbs. Electromyography (EMG) was apparently normal.
Cranial magnetic resonance imaging (MRI) showed Dandy-Walker variant with moderate hydrocephalus. Corpus callosum was stretched. Polymicrogyria in bilateral frontal regions with irregular gray-white matter junction was seen. Hypoplastic pons, inferior vermis with fusion of collicular plates, and cerebellar cysts were present. Delayed myelination in bilateral parieto-occipital and frontal regions was present [Figure 2a and b]. Right eye ball was smaller than the left eye. Muscle biopsy showed dystrophic changes, with excess infiltration of fat and connective tissue on histology and partial reduction of merosin with normal staining of beta-dystroglycan and laminin alpha 2 on immunostaining. Genetic analysis was not feasible and available.
Figure 2.
(a) Magnetic resonance imaging (MRI) sagittal section showing Dandy–Walker variant with moderate hydrocephalus, hypoplastic pons, and inferior vermis with fusion of collicular plates and cerebellar cysts (white arrows). (b) MRI coronal section showing moderate hydrocephalus, inferior vermis with fusion of collicular plates, and cerebellar cysts (white arrows)
Therefore by considering the clinical, ophthalmic, and radiological findings; the diagnosis of an overlap between Walker–Warburg syndrome (WWS) and muscle-eye-brain disease (MEBD) was made. A brief review of literature is discussed below and we can realize the rarity of this condition.
This case illuminates the complexity yet greater understanding of dystroglycanopathies, an emerging area of unique genetic disorders that are manifested with involvement of both central (brain and eye) and peripheral nervous system (skeletal muscle).
The discussion of these disorders in the literature as dystroglycanopathies led to the creation in Online Mendelian Inheritance in Man (OMIM) of a muscular dystrophy-dystroglycanopathy (MDDG) series [Table 1].[1]
Table 1.
Clinical classification of muscular dystrophy-dystroglycanopathies
The precise molecular mechanisms underlying these phenotypic variations are slowly being elucidated. The cause of the muscular, ocular, or brain disorders in these patients is defective formation of basement membranes (of skeletal muscle, retina, and cerebrum/cerebellum, respectively).[2] Table 2 highlights and compares the features in the patient under discussion with the other Cobblestone Lissencephalies.[3,4,5]
Table 2.
Signs in this patient compared with cobblestone lissencephaly
References
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