Özlem KARA, Fatma DEMİREL, Suna EMİR, Meltem TAYFUN, Derya TEPE, Hacı Mehmet DEMİR

Nöroﬁ bromatozis Tip 1 Tanılı Çocuklarda Endokrin Sorunlar

Amaç: Nöroﬁ bromatozis Tip1 (NF 1) klinik bulguları çocukluk çağında ortaya çıkmaya başlayan ve pek çok sistemietkileyen otozomal dominant geçişli bir hastalıktır. Birçok endokrin problem özellikle de büyüme ve püberte sorunları NF1e eşlik edebilmektedir. Bu çalışma ile NF 1 tanılı hastalarımızın büyüme, pübertal sorunlar ve endokrin problemlerinindeğerlendirilmesi amaçlanmıştır. Gereç ve Yöntemler: Kliniğimizde izlenmekte olan 38 hastanın antropometrik, klinik ve laboratuvar verileri geriye dönükolarak incelendi. Bulgular: Çalışmaya 38 olgu alındı, (18 kız, 20 erkek); %55.3ü sporadik, %44.7si ailevi tip NF 1 olgusuydu. Olguların6sında maternal geçiş, 11de paternal geçiş öyküsü vardı. Ortalama başvuru yaşı 10.8 ± 4.4 (2.1 ile 19 yaş) ve 24 hasta(%63.2 ) püberte dönemindeydi. Boy kısalığı 38 hastanın 11de (%28.9), obezite 5 olguda (%13.2), fazla tartılı olma 5olguda (%28.9) saptandı. Püberte bozukluğu 7/38 (%18.4) de olup; 2 gecikmiş püberte, 1 santral püberte prekoks,1prematür telarş,2 prematür pubarş ve 1 pübertal jinekomasti olgusu saptandı. Skolyoz 5 olguda (%13.2) görüldü. Hi- potroidi 3/38 (%7.9) da görüldü; 2 olguda otoimmün troidit, 1 olguda konjenital hipotroidi (dishormonogenezis) vardı. Dvitamini eksikliği ve yetersizliği sırasıyla %44.7 ve %10.5 saptandı.Sonuç: NF 1 hasta grubunda vitamin D eksikliği, obezite, boy kısalığı, erken ve geç püberte en yaygın görülen endokrinsorunları oluşturmaktadır. Bu nedenle NF 1 tanılı hastaların endokrinolojik açıdan periyodik olarak izlenmesi erken tanıve uygun tedavi almalarını sağlayacaktır.

Endocrine Problems in Children with Neuroﬁ bromatosis Type 1

Objective: Neuroﬁ bromatosis type 1(NF1) is one of the most common autosomal dominant multisystem diseases.Many endocrine problems especially related to puberty and growth may accompany NF1. We evaluated growth,pubertal development and endocrine problems in patients with NF1. Material and Methods: We obtained the anthropometric variables, and clinical and laboratory data of 38 patients (18girls and 20 boys) with sporadic (55.3%) or familial NF-1 (44.7%). Six patients had affected mothers and 11 had affectedfathers). The mean age at referral was 10.8±4.4 years (range 2.10 to 19 years) and 24 patients were pubertal (63.2%).The average age at diagnosis was 6.6 years and the mean follow-up period was 4.2 years.Results: Short stature was recognized in 11 of the 38 children (28.9%). One of them had an endocrine disorder(hypothyroidism). Obesity was diagnosed in 5 cases (13.2 %) and another 5 cases were overweight (13.2%). Puberty wasabnormal in 7/38 of the children (18.4%). Two cases of delayed puberty, 1 central precocious puberty (1 male with opticglioma), 1 premature telarche, 2 premature pubarche and 1 pubertal gynecomastia cases were found. Lisch noduleswere seen in 9 cases (23.7%). Scoliosis was diagnosed in 5 cases (13.2%). Hypothyroidism was detected in 3/38(7.9%) children. Two of them had autoimmune thyroiditis and one had congenital hypothyroidism (dyshormonogenesis).The frequencies of vitamin D deﬁ ciency and insufﬁ ciency in the winter were 44.7% and 10.5% respectively. Therevitamin D levels were not adequate in our NF1 patients.Conclusion: Vitamin D deﬁ ciency, obesity, short stature and pubertal disorders were the most common endocrineproblems in our study group. We believe that patients with NF1 should see an endocrinologist routinely.

PDF

___

1. Carmi D, Shohat M, Metzker A, Dickerman Z. Growth, puberty, and endocrine functions in patients with sporadic or familial neuroﬁ bromatosis type 1: A longitudinal study. Pediatrics1999;103:1257-62.
2. Virdis R, Street ME, Bandello MA, Tripodi C, Donadio A, Villani AR, et al. Growth and pubertal disorders in neuroﬁ bromatosis type 1. J Pediatr Endocrinol Metab 2003;16:289-92.
3. Virdis R, Sigorini M, Laiolo A, Lorenzetti E, Street ME, Villani AR, et al. Neuroﬁ bromatosis type 1 and precocious puberty. J Pediatr Endocrinol Metab 2000 ;13:841- 4.
4. Habiby R, Silverman B, Listernick R, Charrow J. Precocious puberty in children with neuroﬁ bromatosis type 1.J Pediatr 1995;126:364-7.
5. Karantza M, Geffner M. Growth and growth hormone in children with neuroﬁ bromatosis type 1. Growth Genet Horm 2005;21:33-8.
6. Alemzadeh R, Lifshitz F. Childhood obesity. In: Lifshitz F, (ed). Pediatric Endocrinology. (4th ed). New York: Marcel Dekker, 2003:823-58.
7. Sağlam H, Tarım Ö. Prevalence and correlates of obesity in school children from the city of Bursa, Turkey. J Clin Res Ped Endo 2008;1:80-8
8. Misra M, Pacaud D, Petryk A, Collet-Solberg PF, Kappy M. Vitamin D deﬁ ciency in children and its management: Review of current knowledge and recommendations. Pediatrics 2008;122:398-417.
9. Conwell LS, Trost SG, Brown WJ, Batch JA. Indexes of insulin resistance and secretion in obese children and adolescents: A validation study. Diabetes Care 2004; 27:314-9.
10. Szudek J, Birch P, Friedman JM. Growth in North American white children with neuroﬁ bromatosis 1 (NF1). J Med Genet 2000;37:933.
11. Boulanger JM, Larbrisseau A. Neuroﬁ bromatosis Type 1 in a pediatric population: Ste-Justines experience. Can J Neurol Sci 2005;32:225-31.
12. Cnossen MH, Stam EN, Cooiman LC, Simonsz HJ, Stroink H, Oranje AP, et al. Endocrinologic disorders and optic pathway gliomas in children with neuroﬁ bromatosis type 1. Pediatrics 1997;100:667- 70.
13. Vassilopoulou-Sellin R, Klein MJ, Slopis JK. Growth hormone deﬁ ciency in children with neuroﬁ bromatosis type 1 without suprasellar lesions. Pediatr Neurol 2000;22:355-8.
14. Nanda A. Autoimmune diseases associated with neuroﬁ bromatosis type1. Pediatr Dermatol 2008;25:392-3.
15. Stevenson DA, Wiskochil DH, Carey JC, Sheng X, Murray M, Moyer-Mileur L. Pediatric 25-hydroxyvitamin D concentrations in neuroﬁ bromatosis Type 1. J Pediatr Endocrinol Metab 2011;24: 169-74.
16. Andıran N, Çelik N, Akça H, Doğan G. Vitamin D deﬁ ciency in children and adolescents. J Clin Res Pediatr Endocrinol 2012;4: 25-9.