Journal of Clinical Research in Pediatric Endocrinology
We present a case study of an year-old boy with Bannayan-Riley-Ruvalcaba syndrome (BRRS) with macrocephaly, lipomatosis, and penile. PDF | The term of Bannayan-Riley-Ruvalcaba syndrome (BRRS) has been suggested first by M. Michael Cohen Jr. in a letter to the American Journal of Medical. Received Date: Accepted Date: J Clin Res Pediatr First described in (1), Bannayan-Riley-Ruvalcaba syndrome (BRRs, OMIM.
Fecal occult blood test was negative. At clinical evaluation, the thyroid gland was noted to be enlarged and US of the gland showed lobes of 40x20x15 mm diameter with nonhomogeneous echotexture, due to several hypoechoic areas of a few millimeters in diameter. Neurologic examination revealed a severe psychomotor retardation, with slow and uncoordinated movements together with proximal limbs asthenia: The analysis revealed a de-novo mutation c. After discharge, the patient was followed up three times a year.
A physical examination, abdominal and thyroid US, endocrinological, orthopedic and dermatological consultations were performed, and fecal occult blood test and laboratory tests including blood cell count and thyroid hormone and antibody levels were assessed at each visit. At the age of 13 years, an arteriovenous malformation was detected in the left hand: It became necessary to perform a percutaneous embolization of the radial artery because it was very dilated 4.
At the age of 14 years, one of the thyroid nodules increased in size, reaching 13 mm in maximum diameter: Total thyroidectomy was performed and histology demonstrated a well capsulated oxyphilic adenoma without capsule invasion or metastases in the lymph nodes. Starting at age 15 years Figure 1the patient also underwent a neuropsychiatric evaluation at each follow-up visit, because of progressive development of the eating disorder and aggressiveness; he was treated with pimozide and delorazepam.
Now, at the age of 22, he is followed up twice yearly. Fecal occult blood test never turned positive, however, a first colonoscopy is scheduled at 23 years. Obesity is severe, with a body mass index value of Every 2 years MRI of the brain is performed. The patient is on substitutive therapy with levothyroxine and assessment of thyroid hormone levels is performed regularly. Neuropsychiatric visits are continued on a monthly basis.
Bannayan Ruvalcaba Riley Syndrome
Case Report B This female patient was referred to our Department because of her suspected syndromic macrocephaly at the age of 5 years and 3 months. She was born at a gestational age of 35 weeks by caesarian section because of premature rupture of membranes. At birth, she weighed g 90th percentile and was 50 cm long 90th percentile with a head circumference of Although development was assessed as normal in her first year of life, a divergence was noted between her length always at 97th percentile and her head circumference, that rapidly increased to exceed the 97th percentile.
Therefore, she underwent brain US several times. MRI revealed dilation of cerebral ventricles. However, her neuropsychomotor development was normal. At age 3 years, an inguinal lipoma developed and its diameter increased up to 3 cm, needing to be removed. At physical examination at age 5 years, the patient was found to have macrocephaly head circumference: Standard karyotype was 46,XX.
A possible diagnosis of BRRs presenting with mild symptomatology was suspected due to the association between macrocephaly and lipoma. Since the time of this diagnosis at age 5 years and 7 months, the patient is being followed up twice yearly.
The follow-up visits include physical examination, orthopedic and dermatological consultations, performing a fecal occult blood test, blood cell count, dosage of thyroid hormone and antibodies, and finally thyroid and abdomen US.
At age 6 years and 7 months, the dermatological assessment revealed development of multiple small subcutaneous lipomas, a few millimeters in diameter, on her chest and abdomen. Thyroid function tests were always normal with negative results for anti-thyroperoxidase and anti-thyroglobulin antibodies.
OMIM Entry - # - COWDEN SYNDROME 1; CWS1
At 8 years of age, abdominal US revealed mild splenomegaly with homogeneous echo texture. Two consecutive thyroid US assessments revealed a growing hypoechoic nodule that rapidly reached a size of 23x9x16 mm, involving the isthmus and left lobe.
Histology demonstrated follicular capsulated adenoma with neither invasion nor nodal involvement. Now she is on substitution therapy with levothyroxine and is followed up twice yearly with thyroid function tests. At the age of 9 years, mild right lumbar scoliosis was noticed during the orthopedic follow-up: Search for fecal blood turned positive at 10 years of age and at the same time microcytic anemia was noticed.
Esophagogastroduodenoscopy and colonoscopy showed 3 pedunculated polyps the largest one was 15 mm in sizein the transverse and descending colons, which were all endoscopically removed. Histology revealed benign hamartomatous lesions with chronic inflammation. At present, this patient is being followed up twice yearly for her iatrogenic hypothyroidism with thyroid hormone dosage and intestinal polyps with fecal occult blood test and abdomen US. Once a year, she undergoes orthopedic, dermatologic and ophthalmologic examinations and MRI of the brain is performed every two to three years.
Now at the age of 12 years Figure 2she is developing well, has no further relapses of lipomas, nor intestinal polyps, her scoliosis does not get worse, has completely normal neuropsychomotor development with brilliant results at school and a fully satisfying quality of life. Discussion BRRs is a pleiotropic genetic condition, encompassing macrocephaly, lipomas, hemangiomas and intestinal polyps, skeletal malformations, and penile glans maculae in males.
Neuropsychomotor development is delayed in approximately half of the patients. All these features combined in different ways may present in a particularly broad phenotypic spectrum.
Currently, diagnostic criteria for BRRs are not universally shared, although the syndrome is usually diagnosed if at least 3 of the 4 major features macrocephaly, lipomatosis, hemangiomas, and speckled penis are found, according to Marsh and Laury et al 10, In some cases, presence of two features are considered sufficient We report two cases, followed up at our Institution, which well illustrate the variability of syndrome presentation, being at opposite ends of its phenotypic spectrum.
Clinical manifestations of the first patient were more severe, including almost all features of BRRs, while in the second patient, macrocephaly was the sole relevant clue to diagnosis and the other features were mild and subtle. A careful work-up of this patient enabled us to detect several other features of BRRs such as follicular adenoma diagnosed by thyroid US and intestinal polyposis by fecal occult blood test and colonoscopy.
Clinical features of the two patients are summarized and compared in Table 1. Findings in patient B strengthen the need for a meticulous evaluation of the clinical manifestations of BRRs, as there may be some cases that present with very subtle features, few signs and no family history of disease. These signs need to be investigated specifically, as was the case in our girl patient. The early recognition of the condition is of paramount importance, mostly because of its oncologic implications.
Actually, affected individuals with PHTS develop both benign and malignant tumors in a variety of tissues, such as breast, uterus and thyroid, and screening procedures for early cancer detection are crucial. Screening protocols are well defined for adult patients with CS, while recommendations for BRRs are less robust It is also important to detect intestinal polyps through fecal occult blood test, eventually followed by colonoscopy.
Due to the higher risk of developing intracranial tumors, periodic brain MRI is also indicated. Of particular interest to pediatric endocrinologists is the involvement of the thyroid gland in patients with BRRs. In fact, both of our cases developed thyroid neoplasm. Besides malignancies, multiple adenomatous thyroid disease and lymphocytic thyroiditis are also frequently encountered in BRRs patients.
In previous series of thyroid nodules in BRRs, mean age at diagnosis was 14 years and our report is consistent with this finding, supporting the need for extend screening recommendations to the pediatric ages, as also suggested by other authors To our knowledge, Hurthle-cell adenoma or carcinoma has never been reported in PHTS and our case represents the first report. Although both our patients developed thyroid neoplasm and underwent total thyroidectomy, in both cases histology revealed the presence of benign neoplasm in spite of suspect cytology.
When this syndrome is not associated with mutations or deletions of the PTEN gene, the cause of the condition is unknown. In some cases, an affected person inherits the mutation from one affected parent.
Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. Males are affected more often than females.
Majority of infants have increased birth weight and length and about half of affected infants have macrocephaly without enlargement of ventricles. Some patients may have intracranial arteriovenous malformations which can bleed.
Growth usually slows during childhood, so affected adults are of normal height and body size. There may be a delay in developmental milestones like speech, sitting, crawling, walking, and low intelligence quotient. Other reported abnormalities include ocular abnormalities like strabismus, widely spaced eyes, and deviation of one eye away from other exotropiaabnormal elevation of optic disc which appears edematous pseudopapilloedema and visual impairment amblyopia.
About a quarter of patients have seizures. In some cases, patients may have musculoskeletal abnormalities like hypotonia, myopathy, hyperextensibility of joints, scoliosis, pectus excavatum, and high arched palate.
Myopathy is thought to be due to abnormal accumulation of lipids within the muscles lipid storage myopathy.
OMIM Entry - ^ - MOVED TO
Other lesions include lipomas and angiolipomas that are seen underneath the skin. Some affected individuals also develop hemangiomas and lymphangiomas. Symptoms develop depending upon the size and location of these lesions. Intestinal polyps may cause bleeding, intussusception, or may prolapse via rectum.