What Is Walker Warburg Syndrome

Introduction

A rare kind of congenital muscular dystrophy that is autosomal recessive and linked to anomalies in the brain and eyes is called Walker-Warburg syndrome (WWS). WWS is distributed all over the world. Since most of the children pass away before they turn three, this is the most severe type of congenital muscular dystrophy. WWS is characterized by generalized hypotonia, muscle weakness, mental retardation, developmental delay, and sporadic seizures at birth. Type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, abnormalities in the eyes, and congenital muscular dystrophy, which is characterized by hypoglycosylation of α-dystroglycan, are linked to it.

The illness name and synonym for walker-warburg syndrome

• Neurological-ocular dysgenesis (COD)
• Muscular dystrophy and cerebroocular dysplasia, or COD-MD, syndrome

Syndrome Chemke

• Syndrome of Hydrocephalus, Agyria, and Retinal Dysplasia (HARD)

HARD +/- illness

• The Pagon Syndrome
• The Warburg syndrome ¹

Epidemiology

The overall incidence of WWS, a rare disease with global distribution, is unknown. According to a survey conducted in northeastern Italy, there are 1.2 incidences for every 100,000 live births. ²

Subtypes

Different CMD subtypes have been identified. There is a pure form of CMD where the central nervous system is not involved. Furthermore,

•  the merosin-deficient type of CMD (MD-CMD)
• Walker-Warburg syndrome (WWS)
•  Muscle eye-brain disease (MEBD) and
•  Fukuyama-type CMD (FCMD)

have been identified as distinct forms of CMD that affect both the central nervous system and the eyes.

 The central nervous system abnormalities comprise different combinations of white matter abnormalities, brainstem and cerebellar malformations, and cerebral cortical dysplasia. Even though much work has gone into developing criteria for the different CMD subtypes, there may still be ambiguity and confusion regarding how to classify a given patient.³

Clinical features of walker–warburg syndrome (WWS)

Common features

• Congenital muscular dystrophy
• Cobblestone (or type II) lissencephaly
• Cerebellar malformation
• Ventricular enlargement
• Hydrocephalus
• Retinal malformation
• Anterior chamber malformation

Facultative features

• Micrognathia/retrognathia
• Cleft lip and cleft palate
• Glaucoma, cataract, microphthalmia, and colobomas
• Encephalocele
• Dandy-Walker malformation
• Low-set malformed ears
• Contractures
• Cryptorchidism, small penis and testis
• Hydronephrosis

Possible association with WWS

• Central and obstructive apnea
• Seizures
• Delayed gastric emptying⁴

Diagnostic methods and criteria

The diagnosis is established based on four criteria

• Congenital muscular dystrophy characterized by glycosylation of α-dystroglycan
• High creatine kinase level
• Anterior or posterior eye anomalies
• Migrational brain defect with type II lissencephaly and hydrocephalus
• Abnormal brainstem/cerebellum

Differential diagnosis

 Fukuyama congenital muscular dystrophy (FCMD) 

• CMD type 1C
• CMD type 1D 
• Muscle-eye-brain disease (MEB) 
• Congenital muscular dystrophies without brain and eye abnormalities⁵

Case study example

The parents of a 9-month-old boy reported that their child had enlarged eyes and a white reflex in both eyes since birth. Upon examination, the child displayed large eyes, low-set ears, frontal bossing, and a white reflex in both eyes. A broad intercanthal distance and a sizable corneal diameter (16 mm × 16 mm in the right eye and 13 mm × 12 mm in the left) were found during the ocular examination. The keratometry readings were 40.4 D × 34.9 D (avg 37.7 D) in the right eye and 40.2 D × 38.6 D (avg 39.4 D) in the left eye. The right eye's axial length measured 30.9 mm, while the left eye's measured 28.8 mm. In the right and left eyes, the anterior chamber depths were 4.86 mm and 4.80 mm, respectively. In the right eye, the lens thickness was 4.99, while in the left eye, it was 4.93. The left eye's corneal thickness measured 436 mm, while the right eye's measured 555 mm. The right 

eye's intraocular pressure was 40 mmHg, while the left eye's was 32 mmHg. The left eye's axial length measured 28.8 mm, while the right eye's measured 30.9 mm. 

These characteristics all pointed to buphthalmos. Both eyes had a complete cataract. There was no evidence of vitreous hemorrhage or retinal detachment on the unremarkable ultrasound of the posterior segment of the eye. Previous records revealed characteristics suggestive of the Dandy-Walker malformation as well as lissencephaly (prenatal ultrasound and foetal magnetic resonance imaging). The abdominal ultrasound came back normal. The child was consanguineous at birth and had significantly delayed milestones. The POM2 gene has the mutation c.1484G>A, according to the genetic analysis.⁶

^Summary

Walker-Warburg Syndrome (WWS) is a severe form of congenital muscular dystrophy associated with brain and eye anomalies. Common features include muscle weakness, developmental delay, cobblestone lissencephaly, cerebellar malformations, hydrocephalus, and retinal abnormalities. Diagnosis is based on criteria including hypoglycosylation of α-dystroglycan, elevated creatine kinase levels, and brain and eye anomalies. It is crucial to differentiate WWS from other congenital muscular dystrophies without brain and eye involvement. A case study illustrates typical clinical manifestations such as buphthalmos, cataracts, Dandy-Walker malformation, and delayed milestones, often present in affected individuals. Genetic analysis can confirm mutations associated with WWS, aiding in accurate diagnosis and management.