HARD is an acronym that stands for Hydrocephalus, Agyria, and Retinal Dysplasia. A very rare and severe autosomal recessive syndrome that becomes quickly lethal. Most of the syndromic children die in the first 3 years of life because of respiratory failure, pneumonia, seizures, hyperthermia, and ventricular fibrillation. It is characterized with major neurologic impairments, including 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. Other features that have been reported in association with HARD Syndrome include coloboma, Persistent Hyperplastic Primary Vitreous (PHPV) also known as Persistent Fetal Vasculature, cataracts, glaucoma, buphthalmos, anterior chamber dysgenesis, optic atrophy, and optic nerve hypoplasia. It is the most severe form of congenital muscular dystrophy with most children dying before the age of 3 years.
Walker-Warburg Syndrome; Warburg Syndrome; Chemke Syndrome; Pagon Syndrome (N.B.: It is different from Pagon Bird Detter Syndrome); Cerebroocular Dysgenesis (COD); Cerebroocular Dysplasia-Muscular Dystrophy Syndrome (COD MD).
Autosomal recessive. Several mutations were found in the protein O-Mannosyltransferase (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein genes.
This condition has a worldwide distribution. The overall incidence is unknown, but a survey in Northeastern Italy has reported an incidence rate of 1.2 per 100,000 live births.
Caused by mutation in the gene encoding protein O-mannosyl transferase. It could be related to a primitive meningeal pathology (neurocristopathy).
Clinical features. Prenatal diagnosis is possible.
The clinical manifestations present at birth are generalized hypotonia, muscle weakness, developmental delay with mental retardation, and occasional seizures. 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.
Precautions before anesthesia
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 ...