Riley-Smith Syndrome

A rare form of PTEN-MATCHS (phosphatase and tensin homologue-macrocephaly, autosomal dominant, thyroid disease, cancer, hamartomata, skin abnormalities) Syndrome. Close to Bannayan-Zonana Syndrome and characterized by macrocephaly, pseudopapilledema, hemangiomata, and multiple lipomas. Subcutaneous hemangioma may be present at birth or appear later in childhood. Multiple signs can be associated (head, chest, abdominal, and genital).

Macrocephaly Multiple Lipomas and Hemangiomata Syndrome; Macrocephaly, Pseudopapilledema and Multiple Hemangiomata Syndrome; Rovsing Syndrome.

First described in 1986 as a different disease. It has been proposed recently that three medical conditions, i.e., the Bannayan-Zonana Syndrome, the Riley-Smith Syndrome, and the Ruvalbaca-Myhre-Smith Syndrome are similar entities and should be most appropriately represented as the Bannayan-Riley-Ruvalbaca Syndrome.

Autosomal dominant.

Not known. Male predominance. However, females can be affected, although in a milder form which explains why it remains mostly undiagnosed.

Results from mutations in the phosphatase and tensin homologue (PTEN) gene. Gene map location is 10q23.3. The homologies displayed by the structure of PTEN suggested to the investigators that it may suppress tumor cell growth by antagonizing protein tyrosine kinases and that it may regulate tumor cell invasion and metastasis through interactions at focal adhesions.

Clinical. It is based on the association of macrocephaly, multiple lipomas, intestinal hamartomatous polyps, vascular malformations, and abnormal pigmentation of the penis. The definite diagnosis is determined genetically.

Multiple signs can be observed with relative frequencies: head anomalies (macrocephaly, scaphocephaly, down-slanting palpebral fissures, strabismus, amblyopia, prominent Schwalbe lines, hypertelorism, exotropia, pseudopapilledema tongue, polyps, high-arched palate), chest anomalies (pectus excavatum, supernumerary nipples), genital anomalies (enlarged penis, enlarged testis), abdominal anomalies (ileal hamartomatous polyps, colonic hamartomatous polyps, intussusceptions, rectal bleeding), neurological anomalies (hypotonia, seizures, thick corpus callosum, intracranial hemangioma), orthopedic anomalies (scoliosis, joint hyperextensibility, macrodactyly), and dermatological lesions (tan macules on the glans and the shaft of the penis, acanthosis nigricans, angiokeratoma, café-au-lait spots, lipomas, hemangiomas, cutis marmorata). The lipomas spontaneously regress with age. Motor and speech development are delayed, mild mental retardation, and incoordination are lifelong features. A myopathy caused by abnormal lipid storage can occur with proved muscle carnitine deficiency. Patients may have an increased risk of intracranial tumors. An increased incidence of Hashimoto thyroiditis has been suggested.

The presence of brain edema and raised intracranial pressure must be assumed until proven otherwise. Proper evaluation of the neurological functions, including CT scan must be obtained before anesthesia. It is essential to check the hemoglobin level and coagulation profile because of the risk of bleeding from the hemangioma. The association with arteriovenous malformations may impact the heart and lead to high output cardiac failure, even in the small infant, it is imperative to assess carefully the cardiac function and obtain an ECG and echocardiogram before induction of anesthesia. The severity of the muscle involvement (myopathy) must be evaluated as well as the respiratory function. Because the thyroid gland can be involved in this process, thyroid hormone level must be measured and appropriate treatment provided before anesthesia.

Difficult direct laryngoscopy and tracheal intubation must be expected in the presence of a high-arched palate. Spontaneous ventilation must be maintained until confirmation that face-mask ventilation can be provided. A laryngeal mask airway should be available in case of a failure to intubate the trachea. Fiberoptic technique for the most difficult cases might be a good alternative. One must be careful with intraoperative positioning (because of the presence of hypotonia, myopathy, and orthopedic deformations). Special precautions have to be provided for the protection of the protruding eyes. Locoregional anesthesia should be carefully discussed with the patient and/or parents because of the presence of an arterivenous malformation (possibly intracranial) which could influence the hemodynamic response. The association with spinal and epidural hemangiomas makes regional anesthesia relatively contraindicated.

It is recommended to avoid the use of succinylcholine because of the association of hypotonia and myotonia. The antiepileptic treatment should be continued to the day of the surgery.

Cowden Syndrome: An autosomal dominant condition with variable expression that results from a mutation in the PTEN gene on the chromosome arm 10q. Associated with hamartomatous neoplasms of the skin and mucosa, gastrointestinal tracts, bones, central nervous system, eyes, and genitourinary tract. The skin is involved in 90 to 100% of cases, the thyroid gland in 66% of cases. It is associated with several types of malignancy, including a marked increase in the incidence of breast and thyroid cancer.

Bannayan-Zonana Syndrome: Closely related to Cowden Disease. An autosomal dominant condition characterized with multiple hamartomas (especially multiple angiomas and multiple encapsulated lipomas), macrocephaly, developmental delay, and hypotonia. However, the incidence of malignancy transformation is very low when compared to Cowden Disease.