Dionisi Vici Sabetta Gambarara Syndrome

Genetic disorder characterized by developmental delay, immunodeficiency, cleft lip/palate, cataract, hypopigmentation, and absent corpus callosum.

Fewer than 10 cases have been reported in the literature.

Autosomal recessive.

Unknown. There is speculation about a defect involving the embryogenic organization of both the CNS and the immune system such as regulating gene products.

Clinical findings and combined immunodeficiency with reduced IgG levels (particularly IgG2 subclass), normal IgA and IgM levels, and low number of circulating T lymphocytes, mainly T4.

Patients present with profound developmental delay associated with agenesis of the corpus callosum, microcephaly, hypotonia, seizures, and, occasionally, severe hypoplasia of the cerebellar vermis. Cortical dysplasia and schizencephaly have been described. One of the main features of this syndrome is a combined immunodeficiency with decreased levels of T4 lymphocytes and serum IgG. This is a result of profound hypoplasia of the thymus and the peripheral lymphoid tissue. Activity of the natural killer cells, however, was reported to be normal. Recurrent infections, particularly pulmonary infections (partially also related to recurrent aspirations) and chronic mucocutaneous candidiasis, are a consequence of this immunodeficiency. The disease is also characterized by hypopigmentation of skin, hair, and retina. Cataract, nystagmus, unilateral or bilateral cleft lip/palate, micrognathia, and postnatal growth retardation are other, but inconstant, features. Cardiac involvement can occur in the form of endocardial fibroelastosis and/or progressive cardiomyopathy with dilatation or hypertrophy of the left ventricle. None of the reported patients has survived beyond age 3 years. Death from cardiac failure has been described, but most often death is the result of bronchopneumonia.

Patients are most often booked for percutaneous gastric tube insertion secondary to failure to thrive. Request a chest radiograph to rule out respiratory tract infection. Obtain an ECG and an echocardiogram if cardiomyopathy is suspected. Continue antiseizure medication up to the morning of surgery.

Airway management may be more difficult than usual because of the micrognathia and cleft lip/palate. Sterile precautions are mandatory for all line insertions because of immunodeficiency. If cardiomyopathy is present, then medical therapy to improve left ventricular function should be optimized before the patient presents for an elective procedure.

Avoid drugs with negative inotropic effect. Avoid or decrease the dose of muscle relaxants in the context of hypotonia. In the presence of a seizure disorder, potentially epileptogenic drugs such as methohexital, ketamine, enflurane, atracurium, cis-atracurium, and meperidine (applies to the latter three only if given in large quantities, because of their metabolites, laudanosine and normeperidine, respectively) should be avoided. Chronic antiseizure medication can lead to induction of hepatic enzymes and therefore accelerate the metabolism of predominantly hepatically eliminated drugs. Antibioprophylaxis should be adapted because of the immunodeficiency.

Aicardi Syndrome: Rare disorder characterized by partial or complete agenesis of the corpus callosum, infantile spasms (spasm-like epilepsy), mental retardation, and an ocular abnormality called lacunae of the retina. Often associated with other features such as microcephaly and porencephalic cysts. Age at onset is generally between 3 and 5 months.

Chediak-Higashi Syndrome: Frequently fatal disease of childhood characterized by albinism, photophobia, hypopigmentation, loss of binocular vision, and marked susceptibility to infections.

Griscelli Syndrome: Albinism with immunodeficiency characterized by partial pigmentary dilution of the skin and hair (silvery gray hair), frequent infections, neurologic abnormalities, and fatal outcome caused by uncontrolled T-lymphocyte and macrophage activation syndrome. Clinical features include the presence of large clumps of pigment in hair shafts and an accumulation of melanosomes in melanocytes.