HARD is an acronym for hydrocephalus, agyria, and
retinal dysplasia. Very rare and severe autosomal recessive syndrome quickly lethal,
with major neurologic impairment. It is characterized by type II
lissencephaly in association with retinal dysplasia, obstructive
hydrocephalus, and agenesis of the corpus callosum. Affected infants
typically have severe growth failure, severe microcephaly, seizures,
microphthalmia, and cataracts.
Walker-Walburg Syndrome; Warburg Syndrome; Chemke
Syndrome; Pagon Syndrome (different from Pagon Bird Detter Syndrome);
Cerebroocular Dysgenesis (COD); Cerebroocular Dysplasia Muscular Dystrophy
Syndrome (COD MD).
Caused by mutation in the gene encoding protein
O-mannosyl transferase. Could be related to a primitive meningeal pathology
Clinical features. Prenatal diagnosis is possible.
Present at birth with polyhydramnios,
decreased fetal movement and growth retardation. It is usually lethal within the
first few months of life. This complex polymalformative disease involves the
head with neurologic malformations (microcephaly, microtia, agyria,
hydrocephalus type II, lissencephaly, corpus callosum and pellucidum
agenesis, disorganized brain cytoarchitecture, cerebellar malformation,
ventriculomegaly and polymicrogyria), ear (absent auditory canals, low-set and
bat ears), eyes (retinal detachment, cataract, microphthalmia, retinal
pigmentary changes, anterior chamber malformation, hyperplastic primary
vitreous, optic nerve hypoplasia, coloboma, glaucoma, and corneal clouding),
and mouth (cleft lip/palate). Profound mental retardation and seizures are
constant. Other features can include imperforate anus, genital abnormalities
(cryptorchidism, small penis and testes), renal dysplasia, congenital
contractures, and muscular dystrophy.
Evaluate neurologic function
(clinical, history, CT, MRI, EEG), renal function (clinical, echography
laboratory investigations including urea, creatinine, electrolytes), and
muscular function (clinical, serum creatine kinase level).
Careful intraoperative positioning is
needed because of contractures and muscular anomalies. Avoid procedures that
can increase intracranial or intraocular pressure, considering the
neurologic and ocular malformations. Ocular signs for measurement of the
depth of anesthesia cannot be used in these patients.
Atropine must be avoided because of
ocular lesions. Consider interaction between antiepileptic treatment and
anesthetic drugs. Succinylcholine use is not recommended because of muscular
dystrophy and risk of hyperkalemic response. Ketamine probably should be
avoided because of its effect on intracranial and intraocular pressure.
HARDE Syndrome (Walker-Walburg Harrod Doman Keele Syndrome):
Presents all the characteristics of the HARD syndrome plus encephalocele.
Lissencephaly, malformation of the cerebellum, mental impairment, seizures,
hypotonia, and eventually spastic quadriplegia accompany the clinical
presentation. Dandy-Walker malformation, cleft lip/palate, microcephaly, and
microphthalmia occasionally present.
Harrod Syndrome: Autosomal recessive condition characterized by
mental retardation, unusual facial appearance, hypotelorism, high arched
palate, numerous genitourinary anomalies, hydrocephalus, and pyloric
Dobyns WB, Pagon RA, Armstrong D, et al: Diagnostic criteria for
Walker-Warburg syndrome. Am J Med Genet
Karadeniz N, Zenciroglu A, Yavuz Gurer YK, et al: De novo translocation
t(5;6)(q35;q21) in an infant with Walker-Warburg syndrome [letter]. Am J Med Genet
Walker AE: Lissencephaly. Arch ...