Balkan Journal of Medical Genetics

MUSCLE HEMANGIOMATOSIS PRESENTING AS A SEVERE FEATURE IN A PATIENT WITH THE PTEN MUTATION: EXPANDING THE PHENOTYPE OF VASCULAR MALFORMATIONS IN BANNAYAN-RILEY-RUVALCABA SYNDROME
Soysal Y, Acun T, Lourenço CM, Marques W Jr, Yakıcıer MC
*Corresponding Author: Assistant Professor Yasemin Soysal, Department of Medical Genetics, Afyon Kocatepe University, Faculty of Medicine, Ali Çetinkaya Kampüsü, Afyonkarahisar, 03100, Turkey; Tel.: +90-5423463576; Fax: +90-2722463300; E-mail: yasemin_soysal@yahoo.com
page: 45

MATERIALS AND METHODS

Clinical Report. The proband was an 8-yearold female, referred to the Neurogenetic Division, University of São Paulo-Clinics Hospital, Ribeirao Preto, São Paulo, Brazil, because of recurrent facial palsy. She was the second child of healthy and non onsanguineous parents. Further family history was unremarkable. She was born by vaginal delivery at term; her birth weight, length, and occipitofrontal circumference (OFC) were not recorded at that time. Her growth parameters were normal during childhood. At 2 years of age, she developed recurrent attacks of facial palsy with full recovery days after the episode; there were no other similar cases in her family. Her medical history included one episode of seizures at 3 years of age, but she did not use anticonvulsants. At 7 years of age, she developed gait problems because of pain in her left leg and was evaluated by an orthopedic surgeon who diagnosed hemangiomas. The hemangioma was excised. After histopathological examination, the lesion was diagnosed as an angiolipoma. However, she had another hemangioma in the same leg several months later. At that time her parents noticed that her leg became thinner. New hemangiomas appeared in her right leg, but the parents decided not to operate until they had a defi nite diagnosis. Her teachers noticed learning disabilities in school. At the age of 8, her weight and height were in the 50th percentile and her OFC was greater than the 97th percentile for her age. Her parents’ OFC were in the normal range. When she was 10, her left leg was amputated because of the hemangioma. On phenotypic inspection, a mild facial dysmorphism consisting of a high forehead, a triangular face, pointed chin, down-slanting palpebral fi ssures, and a high-arched palate were observed. Several verrucae vulgares on her arms and hands and small café-au-lait spots on her arms and trunk were identifi ed. Neurological examination identifi ed a mildly asymmetric face, normal eye movements, brisk osteotendinous refl exes, and no signs of cerebellar ataxia. Interestingly, the patient had facial palsy. The weakness in her left leg included a moderate degree of muscle atrophy and aqueous retraction. Her biochemical and serological tests (including thyroid function and karyotype) were all normal. Electroencephalogram (EEG) monitoring recorded as normal. Electromyography (EMG) revealed the presence of myopathic potential units, but nerve conduction velocities were normal. Abdominal ultrasound monitoring recorded as normal. Magnetic resonance imaging (MRI) of the brain showed a small cavitation on the atrium of left lateral ventricle compatible with increased perivascular space. An MRI of the lower limbs showed normal fi ndings in left leg; her right leg displayed the presence of arteriovenous malformation of the right buttock thorough the right lower limbs and severe muscle atrophy. Because of the combination of macrocephaly, angiomyolipomas, and myopathy, we hypothesized that she might have Bannayan-Zonana syndrome, and performed a thyroid ultrasound and colonoscopy. The thyroid ultrasound showed no abnormal fi ndings; colonoscopy showed a few polyps in the sigmoid colon. The results of biopsy on the polyps were compatible with hamartomatous type lesions. In our patient, the existence of hemangiomas, severe vascular malformation leading to amputation of an extremity, macrocephaly, dermatologic and neurologic fi ndings, and facial dysmorphisms in childhood supported a diagnosis of BRRS and an evaluation of PTEN mutation analysis. After we obtained written informed consent from her parents (Ethical Committee for Medical Research document number 12219/2004), we carried out a direct DNA sequencing of the whole PTEN gene exons. Characterization of the PTEN Mutation. We extracted genomic DNA from peripheral blood leukocytes by means of a commercial kit (QIAamp 51104; Qiagen, Hilden, Germany). We then amplifi ed genomic DNA using primers fl anking the exons of PTEN. Primer sequences and their Tm values are given in Table 1. Reaction conditions were as follows: after initial denaturation at 98C for 1 min., three steps were repeated for 35 cycles (denaturation for 8 seconds at 98C, annealing for 8 seconds at 60C and extension for 15 seconds at 72C). The reaction was fi nished with a fi nal extension for 1 min. at 72C. The polymerase chain reaction (PCR) products were directly sequenced by a sequencing service company, Iontek (Istanbul, Turkey), to detect mutation. We used the Mutation Surveyor software package (v 3.10, SoftGenetics, LLC, State College, PA, USA) for mutation screening.

Number 27 VOL. 27 (2), 2024	Number 27 VOL. 27 (1), 2024
Number 26 Number 26 VOL. 26(2), 2023 All in one	Number 26 VOL. 26(2), 2023
Number 26 VOL. 26, 2023 Supplement	Number 26 VOL. 26(1), 2023
Number 25 VOL. 25(2), 2022	Number 25 VOL. 25 (1), 2022
Number 24 VOL. 24(2), 2021	Number 24 VOL. 24(1), 2021
Number 23 VOL. 23(2), 2020	Number 22 VOL. 22(2), 2019
Number 22 VOL. 22(1), 2019	Number 22 VOL. 22, 2019 Supplement
Number 21 VOL. 21(2), 2018	Number 21 VOL. 21 (1), 2018
Number 21 VOL. 21, 2018 Supplement	Number 20 VOL. 20 (2), 2017
Number 20 VOL. 20 (1), 2017	Number 19 VOL. 19 (2), 2016
Number 19 VOL. 19 (1), 2016	Number 18 VOL. 18 (2), 2015
Number 18 VOL. 18 (1), 2015	Number 17 VOL. 17 (2), 2014
Number 17 VOL. 17 (1), 2014	Number 16 VOL. 16 (2), 2013
Number 16 VOL. 16 (1), 2013	Number 15 VOL. 15 (2), 2012
Number 15 VOL. 15, 2012 Supplement	Number 15 Vol. 15 (1), 2012
Number 14 14 - Vol. 14 (2), 2011	Number 14 The 9th Balkan Congress of Medical Genetics
Number 14 14 - Vol. 14 (1), 2011	Number 13 Vol. 13 (2), 2010
Number 13 Vol.13 (1), 2010	Number 12 Vol.12 (2), 2009
Number 12 Vol.12 (1), 2009	Number 11 Vol.11 (2),2008
Number 11 Vol.11 (1),2008	Number 10 Vol.10 (2), 2007
Number 10 10 (1),2007	Number 9 1&2, 2006
Number 9 3&4, 2006	Number 8 1&2, 2005
Number 8 3&4, 2004	Number 7 1&2, 2004
Number 6 3&4, 2003	Number 6 1&2, 2003
Number 5 3&4, 2002	Number 5 1&2, 2002
Number 4 Vol.3 (4), 2000	Number 4 Vol.2 (4), 1999
Number 4 Vol.1 (4), 1998	Number 4 3&4, 2001
Number 4 1&2, 2001	Number 3 Vol.3 (3), 2000
Number 3 Vol.2 (3), 1999	Number 3 Vol.1 (3), 1998
Number 2 Vol.3(2), 2000	Number 2 Vol.1 (2), 1998
Number 2 Vol.2 (2), 1999	Number 1 Vol.3 (1), 2000
Number 1 Vol.2 (1), 1999	Number 1 Vol.1 (1), 1998

About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact