Bannayan-Zonana Syndrome

Inherited disorder characterized by excessive growth prenatally and postnatally manifesting with macrocephaly and scaphocephaly with normal intelligence or mild mental retardation and multiple hamartomas (lipomas, intestinal polyps). As affected infants age, the growth rate slows down and commonly results in normal adult height.

Bannayan-Riley-Ruvalcaba Syndrome; Ruvalcaba-Myhre-Smith Syndrome.

Unknown, but several case reports exist.

Presumed autosomal dominant inheritance with male predominance (up to 80% of cases). Variability in the severity of the condition in affected individuals suggests allelic mutations or possible genetic heterogeneity. The gene for Bannayan-Zonana syndrome has been localized to the q22-23 region within the PTEN (phosphate and tensin) homologue locus of chromosome 10. The Bannayan-Zonana syndrome should be unified into a single entity with other similar, previously considered separate syndromes, namely, Riley-Smith, Ruvalcaba, Cowden, and Lhermitte-Duclos. Clinical and molecular data support the unification with the proposed new nomenclature PTEN-MATCHS syndrome.

Multiple hamartomas with various angiomatous, lymphangiomatous, and lipomatous constituents. Muscle biopsy demonstrates a lipid storage myopathy with increased depositions of lipid droplets in type I fibers. Type II fibers are smaller than normal. Lipid myopathy may result from a defect in long-chain fatty acid oxidation, which is caused by a deficiency of long-chain L-3-hydroxyacyl-CoA dehydrogenase.

Clinical features and muscle biopsy. Electromyography is consistent with a myopathic condition.

Increased birth weight (>4 kg [8.8 lb]) and length (>97th percentile), with normal adult height are typical. Macrocephaly, macroencephaly, scaphocephaly, and delayed closure of fontanelles. Intracranial manifestations include increased incidence of intracranial tumors, hemangiomas, arteriovenous malformations, hemorrhage, and seizure activity. Extracranial arteriovenous malformations occur. Delayed psychomotor development with dyscoordination, myopathy, and hypotonia. Intelligence may be normal or mildly retarded. Increased salivation and drooling. Ophthalmologic features consist of strabismus (exotropia), hypertelorism, and pseudopapilledema. High-arched palate. Hashimoto thyroiditis has been reported in affected individuals. Pectus excavatum. Juvenile intestinal polyposis with increased risk of intussusception. Protein-losing enteropathy and hepatomegaly may occur. Intestinal and skin lipomas tend to regress with age. Thumbs and great toes are broad (clubbing). Skin manifestations include hemangiomas, multiple lipomas, telangiectases, café-au-lait spots, facial acanthosis nigricans-like discoloration, and cutis marmorata. Penis may be enlarged with spotted pigmentation of the glans. Thyroid and breast tumors may be malignant.

Detailed clinical history and examination to evaluate the extent of systemic involvement: neurologic status, intracranial pathology (tumor, hemangiomata), signs of increased intracranial pressure, seizures (anticonvulsant therapy), and mental retardation (sedative premedication may be valuable in the absence of increased intracranial pressure); cardiovascular status (heart failure secondary to arteriovenous malformation, heart failure medication); and respiratory status (myopathy, hypotonia, degree of pectus excavatum, potential respiratory compromise). Evaluate the airway for potential difficulties (high-arched palate, macrocephaly). Anticholinergic premedication may be beneficial if salivation is excessive. Obtain blood work with complete blood count, electrolytes, urea, liver function tests, and thyroid function tests.

If difficult airway management is anticipated, an awake fiberoptic tracheal intubation (mental retardation may reduce cooperation) or inhalational induction should be considered. Standard neuroanesthetic techniques should be used if an intracranial pathology is present. Spikes in intracranial pressure should be avoided and every effort made to maintain cerebral perfusion pressure. A combination of intravenous induction (thiopental or propofol), opioids, muscle paralysis with controlled ventilation to normoor mild hypocapnia, and maintenance with either isoflurane (<1 MAC) or target-controlled infusion of propofol. Position the head carefully (neutral position) and consider a slight head-up tilt position to assist cerebral venous drainage. Postoperative ventilation may be required for some patients (myopathy, hypotonia, pectus excavatum, neurologic symptoms, intracranial surgery).

Patients receiving anticonvulsant medication should be continued on their regimen until surgery. Postoperatively the medications should be given parentally until oral intake resumes. Succinylcholine should be avoided if possible (myopathy with risk of hyperkalemia), and nondepolarizing neuromuscular blocking agents should be titrated to effect with a peripheral nerve stimulator. Thiopentone is the agent of choice for induction, but propofol, etomidate, and benzodiazepines are acceptable alternatives. Sedative premedication may be helpful, but should be avoided in patients with intracranial pathology (raised intracranial pressure, altered level of consciousness).

Lhermitte-Duclos Syndrome: (Dysplastic Gangliocytoma of the Cerebellum; Benign Hypertrophy of the Cerebellum; Diffuse Ganglioneuroma of the Cerebellar Cortex; Neurocystic Blastoma; Hamartoblastoma, Cerebellar Gangliomatosis; Neurocytoma Myelinicum; Gangliocytoma Myelinicum Diffusum; Purkinjeoma.) Approximately 100 cases have been described. The patients present in young adult age with symptoms of cerebellar dysfunction (absent or only minimal signs in 50%), occlusive hydrocephalus, and signs of increased intracranial pressure. However, symptoms may be present shortly after birth. In approximately 60% of patients, Lhermitte-Duclos syndrome occurs isolated, whereas in the remaining 40% an association with Cowden syndrome can be diagnosed. Magnetic resonance imaging usually confirms the clinical diagnosis. Macroscopically, the cerebellar folia and cortex are enlarged. Histologic examination reveals replacement of the cerebellar internal granular cell layer by large dysplastic neuronal cell bodies resembling Purkinje cells. Prominent myelinated tracts with axonal enlargement in the outer molecular layer of the cerebellar cortex are considered typical.

Cowden Syndrome: A disorder characterized by multiple hamartomas and a risk of breast, thyroid and uterine neoplasias.

Riley-Smith Syndrome: Rare syndrome similar to the Bannayan-Zonana Syndrome characterized by macrocephaly, pseudopapilledema hemangiomata, and multiple lipomas. Subcutaneous hemangioma may be present at birth or appear later in childhood.