Ruvalcaba-myhre-smith syndrome Q85.9

Harris D. Riley and William R. Smith 1960; George A. Bannayan 1961.

There is evidence of germ line mutations in the PTEN gene, which is located on the long arm of chromosome 10.

Men and women are equally affected (Note: in contrast to autosomal recessive inheritance, men and women are equally affected even if they are heterozygous).

Mutation analysis of the PTEN gene using direct DNA sequencing.

Characteristic features of Ruvalcaba-Myhre-Smith syndrome are

• Birth weight of 4 kg and more (with high probability)
• Birth height of 53 cm in girls (with high probability)
• Birth height of 55 cm in boys (with high probability)
• general development disruption/delay
• Macrocephaly (in 50 % of those affected)
• Hemangiomas (at 10 to 40)
• multiple lipomas (at 75 %)
• Melanotic spots (lentigines) on the penis (Freckling)
• Macropenis (possible)
• impaired motor function (at 50 %)
• Muscle weakness (at 50 %)
• Scoliosis (at 50 %)
• Hemi-megalencephaly is less frequently detected (Ghusayni R et al. 2018)
• Immunological dysregulations are possible (Eissing M et al.2019).

With this genetic disposition there is an increased risk of developing thyroid cancer or intestinal carcinoma; women have a higher risk of developing breast cancer.

In individual cases therapy experiments with the immunosuppressive effective Sirolimus were made (Bevacqua M et al. 2019).

The Ruvalcaba-Myhre-Smith syndrome belongs to the group of hereditary hamartoma polyposis syndromes. These clinically overlapping syndromes involve mutations of the PTEN gene. Because of this clinical overlap, they are no longer strictly separated (Hereditary Hamartoma Polyposis Syndromes).

1. Bevacqua M et al (2019) Off-Label Use of Sirolimus and Everolimus in a Pediatric Center: A Case Series and Review of the Literature. Paediatric Drugs 21:185-193.
2. Eissing M et al.(2019) PTEN Hamartoma Tumor Syndrome and Immune Dysregulation. Transl Oncol 12:361-367.
3. Golas MM et al(2019) Looking for the hidden mutation: Bannayan-Riley-Ruvalcaba syndrome caused by constitutional and mosaic 10q23 microdeletions involving PTEN and BMPR1A. At J Med Genet 179:1383-1389.
4. Pilarski R et al (2019) PTEN Hamartoma Tumor Syndrome: A Clinical Overview. Cancers (Basel)11:6
5. Ghusayni R et al (2018) Hemimegalencephaly with Bannayan-Riley-Ruvalcaba syndrome. Epileptic Disord. 2018 Feb 1;20(1):30-34.