One Syndrome, Different Phenotypes: Fragile X Syndrome

Abstract

Aim: The main findings in fragile X syndrome are varying degrees of mental retardation, a long, narrow face, a prominent forehead and chin, and large ears. The purpose of this study was to evaluate patient and family histories, clinical characteristics, laboratory findings, and close clinical follow-up of cases diagnosed with fragile X syndrome.

Material and Method: Clinical and physical examination characteristics and laboratory results of cases diagnosed with fragile X syndrome were evaluated retrospectively.

Results: Five male patients aged 5-14 years were included in the study. Varying degrees of mental retardation and a coarse facial appearance were present in all cases. The most common presentation symptom in our polyclinic was mental retardation. Hyperactivity was present in two patients, self-harm behavior in one, and forgetfulness and enuresis in one. Neuromotor retardation was present in all patients, who were therefore receiving special education, while atypical autism was diagnosed in one case and a history of drug use due to ADHD was present in another. Metabolic, blood count, and biochemical parameters were with normal ranges. Cranial imaging was normal in two patients, while a moderate increase in subarachnoid space in the bilateral hippocampal areas was observed in Case 1, hypoplasia in the splenium and the posterior 1/3 of the body of the corpus callosum in Case 3, and hyperintensity on T2A/FLAIR in the posterior periventricular area in Case 4. No problems were encountered during 6-9-month follow-up. Two brothers of one case were also referred for special education following genetic counseling provided for the families. 

Conclusion: Increasing numbers of patients with undiagnosed mental retardation are presenting to pediatric general and side branch polyclinics. Fragile x syndrome is the first condition that should be considered in patients with a long/narrow face, a prominent forehead/jaw, large ears, macroorchidism, and mental retardation.

Keywords

• childhood,Fragile X syndrome,mental retardation

Bir Sendrom, Farklı Fenotipler; Fragile X Sendromu

Abstract

Amaç: Fragile-X sendromunda değişen derecelerde zihinsel gerilik, uzun ve dar yüz, öne çıkan alın ve çene yapısı, büyük kulaklar temel bulgulardır. Bu çalışmada Fragile X sendromu tanısı konulan olguların özgeçmiş-soygeçmiş, klinik özellikleri, laboratuvar bulguları ve yakın klinik izlemlerinin değerlendirilmesi amaçlanmıştır.

Gereç ve Yöntem: Fragile X sendromu tanısı koyulan olguların klinik ve fizik muayene özellikleri, laboratuvar sonuçları retrospektif olarak değerlendirildi.

Bulgular: Yaşları 5-14 yaş arasında değişen 5 erkek olgu çalışmaya dahil edildi. Olguların tamamında değişen derecelerde mental retardasyon ve kaba yüz görünümü mevcuttu. Hastalarımızın polikliniğe en sık başvuru yakınması zihinsel gerilikti. İki hastada hiperaktivite, bir hastada kendine zarar verme, bir hastada unutkanlık ve enürezis mevcuttu. Çalışmaya dahil edilen olguların tamamında nöromotor retardasyon olduğu ve bu nedenle özel eğitim aldığı, bir olgunun atipik otizm tanısı olduğu, bir hastanın ise DEHAB nedeni ile ilaç kulanım öyküsü olduğu belirlendi. Metabolik, hemogram ve biokimyasal parametreler normal aralıktaydı. İki hastanın kranial görüntülemesi normaldi, diğer hastaların kranial görüntülemesinde; Olgu 1’de bilateral hipokampal alanda subraknoid mesafede ılımlı artış, Olgu 3’te korpus kallosum gövde 1/3 arka kısım ve spleniumda hipoplazi, Olgu 4’te periventrikuler posterior alanda T2A/FLAIR’de hiperintensite izlendi. Olguların 6-9 aylık izleminde herhangi bir sorunla karşılaşılmadı. Ailelere verilen genetik danışmanlık sonrasında bir olgunun iki erkek kardeşinde de Fragile X sendromu tanısı konularak özel eğitime yönlendirildi. 

Sonuçlar: Genel pediatri polikliniği ve çocuk yan dal polikliniklerine her gün çok sayıda tanısı konulamayan mental retarde hasta başvurmaktadır. Uzun/dar yüz, öne çıkan alın/çene yapısı, büyük kulaklar, makroorşidizm ve zihinsel geriliği olan hastalarda ilk düşünmemiz gereken Fragile X sendromudur

Keywords

• çocukluk çağı,Fragile X sendromu,zihinsel gerilik

References

1. Referans 1 Saldarriaga W, Tassone F, Gonzalez-Teshima LY, Forero-Forero JV, Ayala-Zapata S, Hagerman R. Fragile X syndrome. Colombia medica 2014;45:190-198.
2. Referans 2 Verkerk AJ, Pieretti M, Sutcliffe JS, Fu YH, Kuhl DP, Pizzuti A, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell 1991;65:905-914.
3. Referans 3 Crawford DC, Acuna JM, Sherman SL.FMR1 and the fragile X syndrome, human genome epidemiology review. Genetics in medicine 2001; 3:359-371.
4. Referans 4 Hagerman RJ, Hagerman PJ. Fragile X Syndrome. 3rd ed. Baltimore,The John Hopkins University Press. 2002.
5. Referans 5 Turner G, Daniel A, Frost M. X-linked mental retardation, macro-orchidism, and the Xq27 fragile site. J Pediatr 1980;96:837-841.
6. Referans 6 Sobesky WE, Taylor AK, Pennington BF, Bennetto L, Porter D, Riddle J, et al. Molecular/clinical correlations in females with fragile X. Am J Med Genet 1996;64(2):340–5.
7. Referans 7 Pretto DI, Mendoza-Morales G, Lo J, Cao R, Hadd A, Latham G, et al. CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles. J Med Genet 2014;51(5):309–18.
8. Referans 8 Çarman, K.B. Normal neuromotor development of children.Osmangazi Journal of Medicine 2016;38:17-19.

9. Referans 9 Kravis EB. Epilepsy in fragile X syndrome. Developmental medicine and child neurology, 2002;44,724-728.
10. Referans 10 Lozano R, Azarang A, Wilaisakditipakorn T, Hagerman JR. Fragile X syndrome: A review of clinical management. Intractable & Rare Diseases Research 2016;5(3):145-157.
11. Referans 11 Akash Rajaratnam, Jasdeep Shergill, Maria Salcedo-Arellano, Wilmar Saldarriaga, Xianlai Duan, Randi Hagerman. Fragile X syndrome and fragile X-associated disorders. F1000Research 2017, 6(F1000 Faculty Rev):2112
12. Referans 12 Hagerman RJ, Synhorst DP. Mitral valve prolapse and aortic dilatation in the fragile X syndrome. Am J Med Genet 1984;17:123-131.
13. Referans 13 Kronk R, Bishop EE, Raspa M, Bickel JO, Mandel DA, Bailey DB Jr. Prevalence, nature, and correlates of sleep problems among children with fragile X syndrome based on a large scale parent survey. Sleep 2010;33:679-687.
14. Referans 14 Mindell JA, Meltzer LJ, Carskadon MA, Chervin RD. Developmental aspects of sleep hygiene: Findings from the 2004 National Sleep Foundation Sleep in America Poll. Sleep Med 2009;10:771-779.
15. Referans 15 Hatton DD, Buckley E, Lachiewicz A, Roberts J. Ocular status of boys with fragile X syndrome: A prospective study. J AAPOS 1998;2:298-302.
16. Referans 16 Nowicki ST, Tassone F, Ono MY, Ferranti J, Croquette MF, Goodlin-Jones B, Hagerman RJ. The Prader-Willi phenotype of fragile X syndrome. J Dev Behav Pediatr 2007;28:133-138.