Walker-Warburg syndrome caused by mutations in POMT1 gene

*Correspondence: [e-mail].

Abstract

Case Presentation: This case report refers to a male newborn at 39 weeks of gestational age, born from a non-consanguineous couple. The physical exam showed macrocrania, with occipital protuberance, wide anterior fontanel, diastasis of sutures, occipital encephalocele and buphthalmos. Ophthalmological evaluation confirmed congenital glaucoma and cataracts. At the neurological exam we observed reduced spontaneous movement associated with truncal hypotonia, appendicular hypertonia and abolished osteotendinous reflexes. Cranial tomography showed significant lissencephaly and hydrocephalus, probable corpus callosum agenesis, Dandy-Walker variant. Ventriculoperitoneal shunt was implanted on the third day of life due to symptomatic hydrocephalus. The patient presented refractory neonatal seizures related to brain malformation. He received a 20 mg/kg phenobarbital attack followed by maintenance of 5 mg/kg. The Levetiracetam was started due to poor seizure control and abnormalities in neonatal polygraphy. Karyotype by amniocentesis 46, XY and CK 4164 U/L. NGS panel neuromuscular diseases was performed and showed two heterozygous pathogenic mutations in the POMT1 gene.

Discussion: The POMT1 and POMT2 gene are part of the enzymatic complex of the protein O-mannosyltransferase (POMT), present in several tissues, especially in the skeletal striated muscles, brain and testes, where they act in the glycosylation of α-dystroglycan proteins, whose function is to stabilize and protect muscle fibers and direct neuron migration during early development. Mutations in the POMT1 gene are associated to three phenotypes: a severe form of muscular dystrophy (Walker-Warburg syndrome), a slightly less severe muscle-eye brain disease (MEB) and a limb girdle muscular dystrophy-dystroglycanopathy. The Walker-Warburg syndrome is characterized by type II lissencephaly, cerebellar and ocular abnormalities as observed in our patient.

Final Comments: The dystroglycanopathies are a group of rare and complex neuromuscular diseases that need to be considered in the differential diagnosis of patients with brain and eye malformation, being fundamental a careful neurological examination of these patients. The correct diagnosis is essential to organize the patient’s multidisciplinary approach and to offer genetic counselling.

 

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Artikel online veröffentlicht:
12. Mai 2025