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Introduction: Prader-Willi syndrome (PWS) is a genetic disorder caused by the absence of expression of the paternal copy of genes in chromosome region 15q11-13. The genetic subtypes of PWS are deletion (∼70%) and maternal uniparental disomy (mUPD ; 25-30%). Diagnosis was confirmed by methylation test, and genetic subtypes were established using FISH or multiplex ligation-dependent probe amplification and microsatellite analyses. Methods: The sleep unit database was used to analyse all identified cases with PWS (14 patients). Standard overnight polysomnography (PSG) was performed in sleep laboratory. Obstructive sleep apnoea (OSA) was defined by an obstructive apnoea-hypopnoea index, AHI >1/h. Age, symptoms of OSA, tonsillar size and BMI-Z-score were obtained in all cases. Results: Subjects included were 9 months to 11 yrs old. OSA was diagnosed in 11 of 14 (78%) cases, with both obstructive and central apneic events, with mean AHI=7, 0. Those with OSA were significantly older (P < 0.01) and more likely to have enlarged tonsils (P< 0.01) than those without OSA. There was difference in BMI Z-score or the presence of symptoms of OSA, p=0.02. GH was deferred in 5 (36%) pending treatment for OSA Conclusions: OSA was frequently present in children with PWS referred simply to meet the requirement for PSG before starting GH, and indication for operation of enlarged tonsils. We recommend routinely performance of PSG prior to GH therapy, and upper airway surgical intervention. Further studies are necessary to determine optimal treatment for some children with PWS and sleep- disordered breathing.

Pulmonary alveolar proteinosis, (PAP) is a rare disease of unknown etiology, characterized by accumulation of lipoproteinaceous material within alveoli. The prognosis is highly variable, and for over three decades the pathophysiology and treatment of this disease remained a mystery. With recent developments in molecular genetics, our understanding of the pathogenesis of PAP has improved significantly.Four forms of PAP are recognised in children: congenital, acquired, secondary and idiopathic. In adults, and occasionally in older children and adolescents, PAP is usually an autoimmune disease ; antibodies to granulocyte macrophage colony-stimulating factor (anti-GM-CSF) are present in 90 percent of cases. Autoimmune PAP with anti-GM-CSF antibodies has been reported in only a few children, who presented in late childhood or adolescence. Thus, unlike adults with PAP, it appears that the majority of infants and children with PAP do not have the autoimmune form of the disease. As an example, in a study of 15 children with PAP, none had anti-GM-CSF antibodies in the serum, and only one had anti-GM-CSF antibodies in bronchoalveolar lavage fluid. We present a rare case of autoimmune PAP in a 10-year old male patient, diagnosed by HRCT, lung biopsy and lab analyses (positive anti- GM-CSF antibodies in serum). Patient was treated with corticosteroids, hidrochloroquine, GM-CSF and supportive therapy. Lung transplantation was performed one and half year after diagnosis.

Fetal alcohol syndrome prevalence in rural Krapinsko –Zagorska county

We present the results of active case ascertainment of fetal alcohol syndrome (FAS). This study included a sample of urban schoolchildren attending 1st to 4th grade elementary school and their mothers. Out of 912 mothers, 575 (63.04%) participated in the interview. Prenatal alcohol consumption was admitted by 15.47% and binge drinking by 3.13% of interviewed mothers. We evaluated 466 (51.09%) schoolchildren for signs of FAS or partial fetal alcohol syndrome (PFAS) using revised Institute of Medicine (IOM) diagnostic criteria. Nineteen students had features consistent with FAS or PFAS. The observed prevalence of FAS is 3 children and of PFAS is 16 children among 466 students, based on 51% participation rate. The estimated prevalence of FAS is 6.44/1000, of PFAS 34.33/1000 and overall prevalence of FAS/PFAS 40.77/1000. This is the first study of FAS prevalence in Croatia and as far as we are aware the second study in Europe.

Intellectual deficit affects about 1-3% of the population. The cause of mental retardation is unknown in large number of patients and presents significant diagnostic problem. Data from the literature suggest that a proportion of cases are due to constitutional chromosome aberrations, and some 7% are associated to rearrangements of subtelomeric chromosome regions. We present the results of cytogenetic and FISH study in our sample of 55 children with developmental delay. The aim of this study was to determine the frequency and types of subtle structural rearrangements of subtelomeric regions in our group of patients and review the data reported in literature. The children involved in this study had mild to moderate mental retardation, dysmorphic features, malformations, behavioral anomalies, uncomplicated pregnancy and birth. No cases with familial history of mental retardation were included in this study. The analysis was carried out on slides obtained by peripheral blood culture using high resolution GTG-, RBG- and CBG-banding method and commercially available FISH subtelomere screening tool. For understanding the mechanism of origin of structural rearrangement additional analysis using WCP-, CEP- and LSI-probes were performed. All children had normal karyotype at 450-550 band level. Rearrangements involving subtelomeric regions were detected in 4 (7.2%) out of 55 children. There was one familial case, one de novo rearrangement and in two children the parents were not available for cytogenetic and FISH studies. The investigation disclosed one deletion and three unbalanced translocations. This study confirms that rearrangements of subtelomeric chromosome region are significant cause of developmental delay, and that subtelomeric screening and detection of subtelomeric rearrangements in patients with intellectual deficit is important for carrier identification, genetic counseling and prenatal diagnosis.

Dentova bolest

Mukopolisaharidoza tip II (Hunterova bolest) je jedna od sedam tipova danas klasifciranih i prepoznatih mukopolisaharidoza. To je nasljedna bolest čiji se gen nalazi na X kromosomu. Žene imaju dva X kromosoma, od kojih je jedan uredan, dok drugi može nositi promijenjeni gen. Zbog postojanja jednog kromosoma sa zdravim genom, žene ne obolijevaju od MPS II, ali mogu prenijeti oboljeli gen na potomstvo. Ženski potomci mogu biti nositelji bolesti. Muškarci, koji imaju jedan X kromosom, obolijevaju od MPS II ako naslijede od majke nositeljice X kromosom s bolesnim genom. To znači da su uglavnom svi pacijenti koji boluju od ove bolesti dječaci. Postoji i mogućnost nastanka nove mutacije pri čemu majka djeteta nije nositeljica promijenjenoga gena. MPS II pojavljuje se učestalošću 1:155000 živorođene muške djece.

Prenatal care and pregnancy outcome depend on mothers’ health knowledge, educational level, urban or rural surroundings, personal believes and family support. Two most common noxious agents in pregnancy, that can significantly affect its outcome, are alcohol drinking and cigarette smoking. We present the results of a questionnaire done on a sample 656 mothers, living in the centre of Zagreb, a highly urban area. The educational level is high with 41.46% of the mothers finishing high school, 11.28% having a college degree and 44.96% having university diploma. Maternal age span at the time of the study was 26 to 56 years (median 39.5 years). 24% of the mothers admit drinking alcohol and 33% of mothers smokes cigarettes. Although 97% know about the negative effects of alcohol consumption during pregnancy, 13.56% of mothers admitted drinking alcohol during pregnancy, 5% drank alcohol daily during the pregnancy and 2.7% of the mothers engaged at least once during pregnancy in binge drinking. 15.83% of mothers admitted smoking cigarettes during pregnancy, with 1.82% of mothers smoking more than 10 cigarettes per day. Conclusion: we evaluated drinking and smoking habits in an urban and highly educated sample of women. Although the health education and knowledge is high, with almost 2- fold decrease in drinking and smoking habits during pregnancy, there are still 13.56% of mothers drinking and 15.83% of mothers smoking during pregnancy. These data show the necessity for further development and implementation of public health programmes for the prevention of negative pregnancy outcomes.

Mukopolisaharidoze su nasljedne metaboličke bolesti nakupljanja. Pojavljuju se učestalošću od 1:30 000 ljudi. To je heterogena skupina bolesti uzrokovana poremećajem, odnosno manjkom enzima u lizosomima koji su zaduženi za razgradnju mukopolisaharida (glikozaminoglikana - GAG). Mukopolisaharidi su šećeri koji se normalno nalaze u ljudskom tijelu i čine sastavni dio vezivnog tkiva. Zbog nerazgradnje, odnosno djelomične razgradnje mukopolisaharida dolazi do njihova pretjeranog nakupljanja u stanicama i izvanstaničnom tkivu tijela i razvoja bolesti. Mukopolisaharidoze se uglavnom nasljeđuju autosomno recesivno, što znači da oba roditelja moraju imati po jedan oštećeni gen za isti enzim. Roditelji su zdravi, imaju svaki po jedan zdravi i jedan promijenjeni gen za određeni enzim. Dijete ima 25% šanse da nasljedi po jedan bolesni gen od svakog roditelja. Prisutnost oba bolesna gena u djeteta dovodi do razvoja bolesti. Ovisno o enzimima koji nedostaju, dolazi do nakupljanja određene vrste mukopolisaharida i određene kliničke slike. Danas je poznat nedostatak jedanaest vrsta enzima koji dovode do razvoja sedam kliničkih tipova mukopolisaharidoza. To su progresivne bolesti gdje klinička slika ovisi o trajanju bolesti, tj. količni nakupljenih mukopolisaharida u tijelu. Djeca s ovim poremećajem rađaju se zdrava, bez simptoma bolesti, koji postaju vidljivi s vremenom kako dolazi do nakupljanja šećera u tijelu. Mukopolisaharidoze su multiorganske bolesti koje zahvaćaju gotovo sve organe i organske sustave u tijelu stvarajući karakterističnu i tešku kliničku sliku s ranom smrću u dječjoj ili adolescentnoj dobi, ovisno o tipu bolesti i individualnim razlikama među oboljelima. Enzimska aktivnost od samo 0, 1% dovoljna je da klinička slika bolesti bude blažega tijeka.

MPS VI is a rare autosomal recessive lysosomal storage disease due to the arylsulphatase B deficiency. The treatment is now available by replacement of the lacking enzyme (ERT). We present the 18 month follow-up of two affected sibs on arylsulphatase B (Naglazyme) ERT. At the beginning of the therapy the brother M.C. (17) had cardiomyopathy with mitral and tricuspidal regurgitation, asthma with low saturation levels of 89-92%O2, and his stamina was 126 meters measured in the 6/12 minutes walk test (6/12MWT) and 31 stairs measured in the 3 minutes stair climb test (3MSC). His sister V.C. (16) had no signs of pulmonary or cardiac disease, her stamina was 357/735 meters on the 6/12MWT and 117 stairs in the 3MSC. They both had increased liver size, measuring 11 to 12 cm in the midclavicular line, and 4-fold increase in urinary glycosaminoglycans (GAG) levels. After 12 months of treatment, the girl showed marked increase in stamina to 416/864 meters and 131 stairs, increased range of motion (ROM) in 7 joints, a decrease in liver size to 11 cm and a decrease in spleen size to normal. The boy showed significant improvement in the first 12 months with increase of oxygen saturation levels to 95- 98%O2, ROM in 6 joints and stamina to 150.5/252 meters and 56 stairs. However, cardiomyopathy soon progressed rapidly with signs of cardiac failure, decrease in saturation, difficulty in breathing, fatigue and loss of mobility. The condition subsequently significantly improved after the introduction of the adequate cardiac therapy. Conclusion: After 6-month of treatment ERT considerably improved stamina and ROM in our two patients with advanced form of MPS VI disease. Liver and spleen size was also reduced. Urinary GAG levels returned to normal. ERT was in general well tolerated and without serious side effects.

At Children’s University Hospital Zagreb we provide enzyme replacement therapy (ERT) for patients with mucopolysaccharidosis (MPS) type I, II and VI. We report on two patients, a brother M.C. age 16 and sister V.C. age 15, with MPS VI who are undergoing treatment for 7 months ERT with arylsulfatase B (Naglazyme). Before the beginning of treatment the boy had cardiomyopathy, mitral/tricuspidal regurgitation and asthma with low baseline saturation levels. His 6-minute walk test was 126 meters and he was unable to complete the 12-minute walk test (6/12MWT). In 3-minute stair climb (3MSC) test he was able to climb 31 stairs. The girl had no clinical signs of pulmonary/heart disease, 6/12MWT was 357/735 meters, while 3MSC was 117 stairs. Both had evidence of enlarged liver/spleen with enlarged abdominal diameter. Urinary GAG levels were 4 times above normal range. Naglazyme was administered once a week in a dose of 1mL/kg in 250mL saline for 4.5 hours. After six months of treatment both had evidence of greater stamina, increased saturation levels, while 6/12MWT increased to 140/227 meters in the boy and 409.5/836.4 meters in the girl. The 3MSC increased to 60 stairs for the boy and 131 stairs (maximum available) in 2 minutes and 10 seconds for the girl. Liver/spleen size was reduced and shoulder joint mobility increased in both patients. Urine GAG levels returned to normal values. The 6-months follow up of our patients showed that ERT for MPS VI improved endurance, significantly reduced urinary GAG levels and was in general well tolerated.

U Klinici za dječje bolesti Zagreb provodimo enzimsko nadomjesno liječenje bolesnika s mukopolisaharidozom (MPS) tip I., II. i VI. Prikazujemo rezultate jednogodišnjeg liječenja enzimima dvoje bolesnika s MPS VI. - M. C. u dobi 16 godina i V. C. u dobi 15 godina. Prije početka liječenja mladiću je dijagnosticirana kardiomiopatija, mitralna te trikuspidalna regurgitacija i astma sa niskim saturacijama kisika. 6- minutni test hodanja iznosio je 126 metara, a 12- minutni test hodanja nije bio u stanju završiti (6/12MWT). U 3- minutnom testu uspinjanja uz stepenice (3MSC) mogao je prijeći 31 stepenicu. Djevojka nije imala znakova plućne i srčane bolesti, 6/12MWT iznosio je 357/735 metara, dok je 3MSC iznosio 117 stepenica. Oboje su imali povećanu slezenu i jetru uz širi opseg abdomena. Koncentracija GAG u urinu bila je 4x viša od normale. Naglazyme je primjenjivan jednom tjedno u dozi od 1mL/kg u 250mL fiziološke otopine kroz 4.5 sata. Nakon 12 mjeseci liječenja oboje bolesnika pokazalo je veću izdržljivost, višu saturaciju kisika u krvi uz znatno poboljšanje testova hodanja i uspinjanja uz stepenice. Veličina jetre i slezene je djelomično smanjenja, a opseg pokreta je povećan u više zglobova. Koncentracije GAG u urinu vratile su se na normalne vrijednosti. 12- mjesečno praćenje bolesnika s MPS VI. na enzimskoj nadomjesnoj terapiji Naglazymeom pokazalo je da je kod njih došlo do bitnog poboljšanja fizičke izdržljivosti uz značajan pad vrijednosti GAG-a u urinu, a bez težih nuspojava liječenja.

Duchennova i Beckerova mišićna distrofija teške su i progresivne mišićne bolesti koje dovode do slabosti i zatajanja mišića. Brojna istraživanja potvrdila su učinak kortikosterodine terapije na očuvanje mišićne funkcije U ovome radu iznosimo naša iskustva u liječenju pacijenata s DMD-om i BMD-om kortikosteroidom Deflazacortom u dozi 0.6mg/kg/dan u ciklusima kroz 20 dana s 10 dana pauze. Liječenje je provedeno u 2 nepokretna pacijenta s DMD, 1 pacijentom s DMD-om koji je pokretan, ali s izraženim znakovima mišićne slabosti. U terapiju je uključen i 1 pacijent s BMD. Pacijenti su praćeni kroz godinu dana, svaka 3 mjeseca, kada su mjerene mišićna funkcija i snaga te spirometrija. Praćene su nuspojave liječenja mjerenjem tjelesne mase, tlaka, oftalmološkim praćenjem te laboratorijskim pretragama. Povoljni učinci terapije zabilježeni su u 3 bolesnika. Kod jednog nepokretnog pacijenta i pacijenta s BMD tijekom godine dana nije došlo do pogoršanja preostale mišićne funkcije i snage. Kod pokretnog bolesnika s DMD-om javilo se znatno poboljšanje mišićne funkcije – prelazak 10 metara poboljšao se sa 30 na 15 sekundi, uspinjanje uz 4 stepenice sa 40 na 13 sekudni, ustajanje s poda sa 45 na 30 sekundi, dok se ustajanje sa stolice poboljšalo sa 10 na 6 sekundi. Mišićna snaga poboljšala se u 5 mišićnih skupina, a spirometrija je pokazala zadržavanje restrikcijskih smetnji ventilacije na blažem stupnju. Po jedan bolesnik imao je pojavu značajnijeg porasta tjelesne mase te masne kože s aknama. Značajna je pojava početne katarakte u jednoga pacijenta, što još nije opisano kod navedene terapije. Druge nuspojave nisu zabilježene.

Fetalni alkoholni sindrom (FAS) čest je poremećaj koji može imati ozbiljne posljedice za oboljelog, a uzrokovan je konzumacijom alkohola tijekom trudnoće. Kako bi se omogućilo provođenje preventivnih programa, nužno je utvrditi kakva je konzumacija alkohola u žena reproduktivne dobi prije i tijekom trudnoće, jer su takvi podatci nepoznati za našu sredinu. U ovom radu iznosimo podatke o konzumaciji alkohola tijekom trudnoće dobivene anketom majki đaka od 1. do 4. razreda 5-orih zagrebačkih osnovnih škola. Anketu je ispunilo 656 (56.35%) od 1164 majke, u dobi od 26 do 56 godina. Srednju stručnu spremu ima 41.46%, višu 11.28%, a visoku stručnu spremu ima 44.96% ispitanica. Većini (97%) majki poznato je štetno djelovanje alkohola na trudnoću. Rezultati ovog ispitivanja pokazuju da su 33 (5.06%) žene redovito konzumirale do 7 alkoholnih pića na tjedan. Prigodno se opijalo 18 (2.74%) žena, navodeći najviše do 18 opijanja tijekom trudnoće. Podjednaka je konzumacija piva i vina, a samo jedna žena navodi konzumiranje žestokih pića. Tijekom cijele trudnoće pilo je alkohol 30% trudnica. Konzumiranje alkohola potvrdile su 44 (6.07%) od 656 žena. Kad se analiziraju svi odgovori te uzmu u obzir žene koje nisu odgovorile na pitanja ili koje su negirale uzimanje alkohola, a istodobno navele vrstu i vrijeme uzimanja, proizlazi da je kod 89 (13.56%) od 656 žena riječ o potvrđenom ili nesigurnom trošenju alkohola tijekom trudnoće. Učestalost konzumacije alkohola u našoj populaciji podudara se s ispitivanjima na općoj populaciji u SAD-u, te smatramo da učestalost FAS-a u našoj populaciji odgovara zabilježenim razinama od 1-4/1000.

Mucopolysaccharidosis type II (MPS II) is a rare X-linked recessive disorder due to the deficiency of the lysosome enzyme iduronate sulfatase (IDS). This results in the lysosomal accumulation of dermatan and heparan sulfate causing progressive dysfunction of many tissues and organs. Aim: to present clinical phenotype, natural course and management of our patients with MPS II. Patients/Methods: During the last ten years we have diagnosed three patients with MPS II. The diagnosis was made based on clinical criteria, abnormal urinary glycosaminoglycan excretion, deficient serum and/or fibroblast IDS activity, and molecular testing. Results: All patients presented with the severe form of the disease. The delay between symptom onset and first visit to a physician was 21 months, 6 months, and 6 weeks and the gap between the first visit to diagnosis was 5 years, 3 years and 2.5 years respectively. Multidisciplinary approach in the management of MPS II patients was adopted, integrating all aspects of their care, but the results are so far limited. Conclusions: there is a significant gap between early symptoms and diagnosis of MPS II in Croatia. An increased awareness of MPS II among the medical communitiy should help to reduce the diagnostic delay in these patietns. This is particularly important having in view the prospect of enzyme replacement therapy for this disorder.

Neuroblastom je tumor simpatičkog nervnog sistema i može se pojaviti na bilo kojem mjestu tog sustava ; najčešći je ekstrakranijalni solidni tumor dječje dobi ( 8 – 10% zloćudnih tumora djece) ; u 65% bolesnika primarno je smješten u abdomenu gdje se najteže dijagnosticira obično u fazi generalizacije bolesti. Kliničke manifestacije ovise su o anatomskoj lokalizaciji primarnog tumora S obzirom da se brzo širi i često ima loš ishod naročito u grupi srednjeg i visokog rizika potrebno je što ranije postaviti dijagnozu, utvrditi proširenost (stadij) bolesti te primijeniti najefikasniji način liječenja. Od dijagnostičkih pretraga ključne su patohistološka analiza tumorskog materijala, citomorfološka analiza punktata koštane srži ( uzeta s 4 različita mjesta), određivanje bioloških markera NSE, LDH, feritin, VMA, HVA, te N-MYC, delecija kromosoma 1p, kromosom 17q, P-glikoprotein, BCL-2 onkogen, telomeraza, TrkA, MIBG (metajodbenzilgvanidin), kompjuterizirana tomografija, nuklearna magnetska rezonanca. Metode kao i rezultati liječenja ovise o prognostičkoj skupini bolesnika i o stadiju bolesti. U prognostički najpovoljnijoj skupini bolesnik se samo opservira, dok u rizičnijim skupinama prima kemoterapiju u kombinaciji s kirurškim zahvatom, zračenjem, i autolognom transplantacijom koštane srži. U radu se iznose nove mogućnosti liječenja te postignuti rezultati.

Zadnjih desetak godina došlo je do velikog napretka u dijagnostici i liječnjue dječjih malignih (zloćudnih) bolesti. Najveći napredak nastao je u liječenju dječijih leukemija tako da se većina djece s neukemijom može danas izliječiti. U radu se iznose principi dijegnostike i liječenja dječijih leukemija.

Mukopolisaharidoza tip I (MPS I ) je lizosomska bolest kod koje, zbog nedostatka alfa-L-iduronidaze, dolazi do nakupljanja glikozamionoglikana – dermatan i heparan sulfata te progresivnog propadanja brojnih organa i organskih sustava. U ožujku 2003. počeli smo s primjenom nadomjesne enzimske terapije (laronidaza) u dvoje djece – devetogodišnjeg dječaka i osmogodišnje djevojčice, kod kojih se roditelji nisu odlučili na transplantaciju koštane srži u ranom stadiju njihove bolesti. Progresija bolesti dovela je kod oboje do postupnog oštećenja brojnih organa i organskih sustava: vida, sluha, kroničnih upalnih promjena dišnog sustava sa čestom opstrukcijom, poremećaja spavanja sa sindromom sleep apneja, hepatosplenomegalijom te kontrakturama zglobova. Kod dječaka je bila oštećena i srčana funkcija (NYHA II). Intelektualno funkcioniranje je također bilo zahvaćeno u oboje, više kod djevojčice. Kako je opća suportivna terapija imala ograničeni učinak, uvedeno je enzimsko liječenje. Dobrobit liječenja enzimom uključivala je poboljšanje u općoj fizičkoj kondiciji i raspoloženju, normalizaciju obrasca spavanja, nestanak sindroma sleep-apneja te smanjenje hepatosplenomegalije. Povećanje pokretljivosti zglobova većinom je bilo ograničeno na zapešća i kukove. Uz to su u jednog ili oboje bolesnika uočeni poboljšanje sluha, oštrine vida, srčane funkcije i reguliranje stolice. Ireverzibilne koštane promjene nisu se pogoršale. Kod dječaka je intelektualno funkcioniranje zadržano na razini prije liječenja, a kod djevojčice su se razvile neurološke komplikacije MPS I. Smatramo da opcija enzimskog nadomjesnog liječenja ne bi trebala biti isključena ni u bolesnika s Hurlerovim sindromom, kod kojih nije učinjena transplantacija koštane srži. Terapijski ciljevi u teških bolesnika su stabilizacija ili poboljšanje mnogih simptoma bolesti te poboljšanje kakvoće života.

Maligne bolesti su jedan od vodećih uzroka smrti u djece Europe i Amerike. Zadnjih desetak godina učinjen je bitan napredak kako u dijagnostici tako i njihovom liječenju, naročito u liječenju malignih limfoma. Uvođenjem novih metoda liječenja (nove kombinacije citostatika, zračenja, kirurškog zuahvata, nonklonskih antitijela te transplantacije koštane srži) u ovih bolesnika danas je moguće postići visok postotak dugotrajnih remisija i izljiečenje.

Malignant diseases are the second leading cause of mortality in children, secondary only to traffic and other accidents. Leukemias are the most common malignancy in children. In the last decade, great advances have been made in the diagnosis and management of malignant diseases of childhood, with highest achievements in the treatment of leukemia in children. Thus, the majority of children with leukemia can now be successfully treated. The principles of diagnosis and treatment of leukemias in children are presented.

Zloćudne su bolesti nakon nesretnih slučajeva vodeći uzrok smrti djece u Evropi i Americi. Nove metode dijagnostike i liječenja značajno su poboljšale rezultate tako da se danas petogodišnje preživljenje djece sa zloćudnim bolestima postiže u 78% bolesnika. Detaljnije su prikazane neuroblastom, leukemije i tumori bubrega.

Malignant diseases are one of the most common causes of mortality in children in Europe and America. In the past ten years, considerable advancement has been achieved in both the diagnosis and treatment of these diseases, malignant lymphoma in particular. With the introduction of new therapeutic modalities (new combinations of cytostatics, radiotherapy, surgery, monoclonal antibodies, and bone marrow transplantation), a high rate of long-term remission and recovery is now possible to achieve.

Do uvođenja nadomjesne enzimske terapije, liječenje teških bolesnika s mukopolisaharidozom tip I (MPS I) koji nisu bili podvrgnuti transplantaciji koštane srži ili koji su odbacili transplantat, bilo je ograničeno isključivo na pokušaje palijativnog ublažavanja simptoma bolesti u progresiji. Prikazujemo rezultate nadomjesne enzimske terapije u dva bolesnika, devetogodišnjeg dječaka i osmogodišnje djevojčice u uznapredovalom stadiju teškog oblika bolesti (Mb. Hurler). Bolesnici su primali infuzije laronidaze u tjednim razmacima, u dozi od 100 U/kg tjelesne težine. Kliničko stanje tijekom liječenja procjenjivano im je detaljnom kliničkom i laboratorijskom obradom. Nadomjesna enzimska terapija bila je najdjelotvornija u liječenju poremećaja spavanja i sleep apnoea sindroma, redukciji veličine jetre, slezene i bubrega te poboljšanju općeg fizičkog stanja i raspoloženja. Povećao se opseg pokreta u nekim zglobovima, poboljšali su se vid, sluh te funkcija probavnog sustava. Nadomjesna enzimska terapija nije imala utjecaja na bolest središnjeg živčanog sustava.

Acute leukemias are dominant malignomas in children and are characterized by marked biologic heterogeneity. Some 85% of childhood hemoblastoses are acute lymphoblastic leukemias (ALL), while acute nonlymphocytic leukemias (ANLL) are less frequent. In this work we present the results of cytogenetic investigation in our group of children with acute leukemias. The aim of this investigation is to determine the frequency and types of acquired chromosomal abnormalities in different morphologic subtypes of disease in relation to the age of patients. Our study has included 55 children with ALL and 30 children with ANLL. The patients were separated into three groups according to age: 0-1, 1-10 and 10-15 years. The investigations were performed on slides obtained by short term bone marrow culture and stained by G- banding method. Clonal chromosomal aberrations were detected in 63% and 64% of children with ALL and ANLL repectivelly. Abnormalities were identified in each of three age groups, however, the frequency of acquired abnormality was different between the groups. In children with ANLL the highest frequency of clonal aberrations was observed in the group from 1-10 years (74%) while the frequency decresed in older patients. The clonal abnormalities were identified in all three children with ALL up to 12 months old, and in 86% of children older than 10 years at diagnosis. Comparison of our data with that from the literature revealed some differences and similarity. This hetrogeneity may be attribute to the differences in the methodological approach and to the biological variability between different geographic and ethnic groups.

We present the data on the registration of limb defects in four Croatian regions (Varaždin, Rijeka, Pula and Koprivnica) collected on the bases of the EUROCAT methodology and processed in the Referral Centre of the Ministry of Health for Surveillance of Congenital Anomalies of the Republic of Croatia in the Children's University Hospital Zagreb. The total prevalence of congenital anomalies in the Croatian registry was 16.32/1000 births, which is consistent with the EUROCAT registry prevalence – 21.62/1000 births. Limb defects were the most common, with a total of 318 cases (51.22/10000 births compared to 37.60/10000 births on the EUROCAT registry). Hip dislocation and pre-dislocation conditions were most frequently diagnosed (137 cases – 22.11/10000 births), followed by the talipes equinovarus, equinovalgus, calcaneovarus and calcaneovalgus group with a total of 95 cases (15.33/10000 births), polydactyly (50 cases – 8.23/10000 births) and syndactyly 18 cases (2.91/10000 births). We also observed 24 cases of limb reduction defects (3.87/10000 births), together with 8 cases of ADAM complex. 17 cases (5.35%) were associated with at least one other major congenital defect and in 21 cases, the limb defect was part of a specific syndrome. During the ten-year period we observed no clusters, only periodical fluctuations in the prevalence of a particular limb defect. A rapid decrease in the prevalence of polydactyly was noted (from 9.78/10000 births in the 1992-1996 period to 6.65/10000 births in the 1996-2001 period). The total prevalence of congenital anomalies in Croatia is in consistency with the EUROCAT registry. The prevalence rate of limb defects is slightly higher compared to the EUROCAT prevalence. Taking into consideration the fact that polydactyly is easily diagnosed and that its prevalence is not liable to methodological errors, the aetiology of the detected decrease is interesting for further research.

The cytogenetic analyses of children's solid tumours are rare, due to low proliferative activity and difficulty in obtaining adequate number and quality of mitotic cells. In this study we present the results of cytogenetic analysis in 15 children with solid tumours. The aim of this study is to identify numerical and structural chromosome aberrations, and to determine the feasibility of using the interphase FISH method in the investigation of genomic imbalances. Cytogenetic investigations were performed on slides obtained by direct method of tumour tissue treatment. GTG- and CBG- banding method were used for chromosome identification. FISH analysis was carried out using locus specific and chromosome specific centromeric probes (Vysis). Analyzable metaphases were obtained from 14 specimens, and in one tumour the data on genomic imbalance were obtained by interphase FISH. Clonal chromosome abnormalities were found in 14 cases, while in one tumour normal diploid karyotype was identified. Most tumour presented numerical aberrations ranging from near-diploidy to near-octoploidy. Double-minute chromosomes were identified in three specimens, ring and telomere fusions in one. Aberrations of chromosome No. 1 were the most frequent clonal rearrangements. Interphase FISH revealed N-myc amplification in one out of three investigated samples and loss of the short arm of chromosome 17 in one patient. Our early results confirm that FISH is not suitable for initial screening of chromosomal aberrations in solid tumour, but is a valuable tool for detecting tumour-specific chromosomal aberrations that have diagnostic and prognostic significance.

Carey-Fineman-Ziter syndrome is a very rare disorder characterized by a dysmorphic face, Moebius and Robin sequences, congenital myopathy, and growth retardation. Skeletal anomalies and developmental delay are occasionaly present. Only 6 patients have been described so far, two sporadic cases and two pairs of siblings suggesting autosomal recessive inheritance. We report a 9-year old girl with remarkably similar anomalies. Her unusual facial features included high forehead, prominent metopic suture, antimongoloid eye slanting, strabism, high myopia, low-set, poorly shaped ears, hypoplastic alae nasi, short philtrum, cupid shaped, short upper lip, small mouth with receding angles, and Robin sequence. She also had Moebius sequence resulting in distinct functional abnormalities involving eye movement, facial expression, mouth closure, speech and swallowing. During early infancy difficulties in sucking, failure to thrive and marked hypotonia were noted. Shehad bilateral talipes equinovarus with hyperlaxity of other joints. Neurological evaluation showed multiple lesions of the cranial nerves, predominantly n. abducens, and bilateral facial nerve palsy, striking atrophy of the lower leg muscles, reduced deep-tendon reflexes and signs of lower motor neuron lesion on EMG which have not been observed in reported patients so far. Her mental development was within the normal range, although motor defecit, slow speech development, short attentiion span, hyperactivity and disturbances of visual and motor organisation and integration were noted. Our patient delineates the features of Carey-Fineman-Ziter syndrome confirming the Moebius-Robin Sequence associatin to congenital neuromuscular disorders.

We describe a girl diagnosed with GM1 gangliosidosis based on clinical characteristics, and biochemical findings typical for the disease – a low level of beta-galactosidase in the leukocytes and increased excretion of urinary oligosaharides and keratane sulphate. Slight dysmorphic features and laryngeal stridor were already present at birth. At the age of 13 days she was hospitalized for pneumonia., followed by numerous respiratory infections in the subsequent months. Extreme hypotonia was noted, which is in contrast to the rigospasticity typical for the disease. She showed marked psychomotor delay. A CT-scan revealed significantly widened subarachnoidal spaces and ventricles. At the age of 11 months, lumbar kyphoscoliosis and hepatosplenomegaly were observed. She died at the age of 18 months due to the cardiomyopathy and cardiorespiratory failure.

Acute myeloid leukemia (AML) is a heterogeneous group of disease involving differences in cell morphology, immunophenotype, clinical response to the treatment, and cytogenetic abnormalities. In this work we present the results of cytogenetic analysis in 35 children with acute myeloid leukemia. The aim of our investigations was to determine the frequency and types of clonal chromosomal rearrangements in our population of children with AML. The investigation was performed on slides obtained from a 24-hour peripheral blood or bone marrow cultures. For chromosome identification GTG- and CBG- banding method were used. A successful analysis was obtained in 32 (91.4%) children. In 30 children the analysis was performed at diagnosis and in two at relapse. Clonal chromosomal aberrations were detected in 19 (63.3%) children at diagnosis. The most frequent clonal abnormality was t(8 ; 21) identified in 6 (20%) patients, followed by aberrations involving chromosome 11 in 4 (13.3%) cases. Trisomy 8 was identified in two and monosomy 7 in one patient. Beside these recurrent abnormalities some non-specific rearrangements were identified too. This study confirms the cytogenetic heterogeneity of AML, and need for additional study in order gain more information on clonal chromosomal rearrangements and its clinical significance.

Carey-Fineman-Ziterov sindrom izuzetno je rijedak autosomno recesivni poremećaj, koji obilježavaju dismorfične crte lica, Moebiusova i Robinova sekvenca, kongenitalna miopatija i zastoj rasta. Uz ove osnovne simptome mogu se naći i koštane anomalije te razvojno zaostajanje. Prikazujemo 9-godišnju djevojčicu s ovim poremećajem. Tijekom ranog djetinjstva imala je poteškoće kod sisanja, zaostajanje u tjelesnom napredovanju, izrazitu hipotoniju te ekvinovarus obaju stopala i hipotrofiju potkoljenica. Uz neobične crte lica i Pierre Robinovu sekvencu, prisutne su i smetnje u funkciji očnih mišića, muskulature lica, otežano zatvaranje usta, artikulacija i gutanje. Uz obostranu parezu n. abducensa i n. facijalisa, kod djevojčice se na EMNG-u registriraju znaci lezije donjeg motornog neurona. Njen je intelektualni razvoj unutar normalnog raspona, premda postoje motorički deficit, otežan govor, skraćen opseg pažnje, hiperaktivnost i poremećaji u vizualnoj i motornoj organizaciji. Ova bolesnica upućuje na postojanje povezanosti Moebiusove i Robinove sekvence s neuromuskularnim poremećajima i proširuje klinički spektar sindroma Carey-Fineman-Ziter.

To determine the efficacy of the enzyme replacement therapy with rh-alpha-L-iduronidase (Aldurazyme) in two patients with Mb. Hurler, the most severe form in the clinical spectrum of Mucopolysaccharidosis type I. Rh alpha-L-iduronidase has been administrated weekly, 100 IU/kg. At the beginning of the treatment, both patients, a nine-year-old boy and an eight-year-old girl, were at the advanced stage of the disease. After 13 months of the therapy, the boy showed an improvement in general physical condition, respiratory function and mobility, as well as the reduced hearing impairment. The sleep-apnea syndrome disappeared, together with all other sleeping disorders. The results of the urinary GAGs became normal and the leukocyte alpha-L-iduronidase reached the therapeutic level. The girl showed a similar improvement in the first six months of the treatment, but a relative stagnation in her clinical condition followed. A gradual decrease of leukocyte alpha-L-iduronidase concentration was also noted. The enzyme replacement therapy has demonstrated positive clinical results in our patients, but a constant monitoring of the clinical and biochemical parameters is necessary for a proper evaluation of the treatment efficacy.

Registri prirođenih mana u svijetu i Hrvatskoj počeli su se osnivati nakon što se posljednjih desetljeća uočila važnost prirođenih anomalija u strukturi morbiditeta i mortaliteta dojenčadi te uvidjela korist podataka dobivenih ovakvim oblikom epidemiologijskih ispitivanja. Na svjetskoj razini osnovan je ICBDMS, dok je na onoj europskoj osnovana mreža regionalnih registara EUROCAT-a, sa specifičnim ciljevima i standardiziranom metodologijom. Registar EUROCAT-a sakuplja informacije o prirođenim manama te na temelju tih podataka omogućava istraživanja, olakšava rano otkrivanje izloženosti teratogenima i identifikaciju nakupljanja prirođenih mana u vremenu i prostoru, pomaže u evaluaciji prenatalnog probira te daje poticaj za širenje kvalitetne mreže registara koji prate rijetke genetičke poremećaje. Hrvatski registar, sa središnjicom u Referentnom centru Ministarstva zdravstva za praćenje kongenitalnih anomalija Republike Hrvatske u Klinici za dječje bolesti Zagreb, djeluje kao članica projekta EUROCAT od 1983. godine. Praćenje trenutno obuhvaća četiri hrvatske regije - Varaždin, Rijeku, Pulu i Koprivnicu, a širenje registra na područje cijele Hrvatske omogućilo bi kvalitetnu evaluaciju učinkovitosti javnoozdravstenih preventivnih programa, te značajno poboljšanje u planiranju kvalitete i nadzora zdravstvene zaštite naše populacije.

Preliminarni rezultati pokazuju da je trećina od dosad analiziranih bolesnika s nesindromskom perceptivnom gluhoćom homozigotno ili heterozigotno za najčešće mutacije u GJB2 genu. Predložen je dijagnostički postupnik obrade slušnog oštećenja. Ispitivanje etiologije gluhoće u Hrvatskoj omogućiti će učinkovitije planiranje dijagnostičkih i preventivnih programa za zaštitu zdravlja djece sa oštećenjem sluha.

BACKGROUND Lymphomas are relatively frequent form of malignant disease in children. The disease is characterized by marked biologic heterogeneity. The heterogeneity of malignant lymphomas has been confirmed by morphologic, immunologic and cytogenetic analyses. In the past 20 years cytogenetic studies revealed different chromosomal abnormalities specific for lymphomas. Investigations carried out so far have mostly dealt with population of adult patients, whereas studies in children with lymphomas are still rare. OBJECTIVES The aim of this investigation was to define the frequency and types of clonal chromosomal abnormalities of malignant cells in our group of childhood non-Hodgkin's lymphoma. METHODS Our investigation included 16 children, 4 girls and 12 boys aged from 9 months to 15 years. Using cytological (FNA biopsy, exfoliative or imprint method) and histopathological methods of deep paediatric lesion, ascites, pleural drain or intraoperative material we diagnosed lymphoma. Cytogenetic analysis of malignant cells was carried out at the time diagnosis was made, before initiating therapy. Slides were obtained from direct or short -term culture of lymph node and/or bone marrow cells. Chromosome identification was carried out using the G-banding method. Chromosomal abnormalities were described according to the International System for Human Cytogenetic Nomenclature (1991). RESULTS The results of cytological and histopathological diagnosis were compared. Correlation of the results was markedly high. Cytogenetic analysis revealed clonal chromosomal abnormalities in 11 (68, 7%) out of 16 children. Chromosome instability and evidence of clonal evolution were observed in 3 patients. Pseudodiploid clone was observed in 4, hyperdiploid in 5 and hypotriploid in 2 out of 11 children with clonal chromosomal aberrations. This investigation revealed complex numerical and structural aberrations. The gains of some chromosome types were nonrandom and frequently affected chromosomes were 11, 14, 21 and X. Involvement of particular chromosome type in structural abnormalities was nonrandom too. Chromosome No.1 and No. 14 were abnormal in 5 and 4 cases respectively. CONCLUSION This investigation confirms variability of clonal chromosomal aberrations and cytogenetic heterogeneity of childhood non-Hodgkin lymphomas. Additional investigations are however, necessary to define more precisely the frequency and types of aberrations, and biological role of chromosomal regions in the development of NHL.

Acue myeloid leukemia (AML) is a heterogeneous group of disease involving differences in cell morphology, immunophenotype, clinical response to the treatment, and cytogenetic abnormalities. In this work we present the reuslts of cytogeneic analysis in 35 children with acute myeloid leukemia. The aim of our investigations was to determine the frequency and types of clonal chromosomal rearangements in our population of children with AML. The investigation was performed on slides obtained from a 24.hour peripheral blood or bone marrow cultures. For chromosome identification GTG- and CBG- binding method were used. A successful analysis was obtained in 32 (91.4%) children. In 30 children the analysis was performed at diagnosis and in two at relaps. Clonal chromaosomal aberrations were detected in 19 (63, 3%) children at diagnosis. The most frequent clonal abnormality was t(8 ; 21) identified in 6 (20%) patients, followed by aberrations involving chromosome 11 in 4 (13, 3%) cases. Trisomy 8 was identified in two and monosomy 7 in one patient. Beside these recurrent abnormalities some non-specific rearrangements were identified too. This study confirms the cytogenetic heterogenity of AML and need for additional study in order to gain more information on clonal chromaosomal rearrangements and its clinical significance.

Angelmanov sindrom (AS) je neurologijski poremećaj koji nastaje kao posljedica disrupcije u regiji 15q11.2-q13 podrijetlom od majke. Do gubitka funkcije ove regije može doći uslijed delecije, uniparentne disomije, mutacija gena UBE3A, oštećenja/poremećaja genomskog upisa, raznih kromosomskih aberacija koje zahvaćaju ovu regiju, a u dijelu bolesnika etiologija nije razjašnjena. Klinička slika bolesnika sa Angelmanovim sindromom je varijabilna. Nerijetka su preklapanja simptoma ove bolesti sa simptomima drugih poremećaja kao što su neke mikrodelecije ili mikroduplikacije, Rettov, Prader-Willijev, ATR-X i Gurrierijev sindrom, mutacije u FRAXA i FRAXE genu, idiopatska neprogresivna encefalopatija, Lennox Gastaut, te pervazivni razvojni poremećaji. Simptomi se razvijaju postupno tako da ovise o dobi pacijenta, a također i o genetičkom mehanizmu nastanka disfunkcije kritične regije. Smatra se da najtežu i tipičnu kliničku sliku imaju bolesnici s delecijom. Prikazujemo 3.5 godišnjeg dječaka s razvojnim zaostajanjem i blagom kliničkom slikom AS kod kojeg je FISH analizom dokazana delecija 15q11.2-q13. Dajemo pregled i genotipsko-fenotipsku korelaciju dosad opisanih blagih i atipičnih oblika AS.

Mukopolisaharidoza tip I (MPS I) nasljedni je poremećaj uzrokovan nedostatkom lizosomnog enzima α -L-iduronidaze, koji sudjeluje u razgradnji glikozaminoglikana (GAG). Djelomično razgrađeni GAG nakupljaju se u stanicama i tkivima raznih organa i sustava dovodeći postupno do njihovog oštećenja. Mogućnosti djelotvornog liječenja još se istražuju. Prikazujemo rezultate 16-mjesečnog nadomjesnog liječenja rh alfa-L-iduronidazom dvoje naših bolesnika s MPS I - devetogodišnjeg dječaka i osmogodišnje djevojčice. Kod početka liječenja oba su bolesnika bila u uznapredovalom stadiju bolesti. Rh α -L-iduronidazu smo primijenjivali jednom tjedno, u dozi od 100 IU/kg. Za vrijeme liječenja nisu primijećene nuspojave niti alergijske reakcije. Kod dječaka je uočeno poboljšanje u općem fizičkom stanju, respiratonoj funkciji, bolji sluh te povećana pokretljivost zglobova. Sleep-apnea epizode više se ne bilježe, a nestali su i drugi znakovi poremećaja spavanja. Razina α -L-iduronidaze u leukocitima dosegla je terapijske vrijednosti, a GAG u mokraći su unutar normalnog raspona. Kod djevojčice je u prvih mjeseci zapaženo istovjetno poboljšanje, no u posljednjih nekoliko mjeseci ponovno su se javile infekcije gornjeg dišnog sustava, kao i poremećaji spavanja, a smanjila se i opća pokretljivost zglobova. Zabilježeno je i postupno smanjenje koncentracije alfa-L-iduronidaze u leukocitima. Naše opažanje ukazuje na to da nadomjesna terapija MPS I bolesnika zahtijeva trajnu kliničku i biokemijsku evaluaciju.

Gangliozidoza tip I (GM1) je autosomno recesivna bolest uzrokovana taloženjem gangliozida i oligosaharida u lizosomima uslijed nedostatka enzima belta-galaktozidaze. Fenotipsko očitovanje je raznoliko, te razlikujemo infantilni, juvenilni i odrasli oblik bolesti. Prikazujemo djevojčicu s teškim infantilnim oblikom GM1. Rođena je iz 5. majčine trudnoće. Tri su trudnoće završile spontanim pobačajem ili mrtvorođenjem, a iz jedne se rodilo muško dijete koje se uredno razvija. Djevojčicu smo imali prilike pregledati u dobi od 13 mj. kada su zapaženi neproporcionalno smanjeni rast, Hurlerin fenotip, hepatosplenomegalija, te zaostajanje u psihomotornom razvoju, hipotonija i hipotrofija. Klinička sumnja na GM1 potvrđena je biokemijskim nalazima - niskom razinom beta galaktozidaze u leukocitima i povećanim izlučivanjem oligosaharida i keratan sulfata u urinu. Bolesnica je umrla u dobi od 18 mjeseci uslijed kardiorespiratornog zatajenja. DNA analiza galaktozidaza beta 1 gena otkrila je da je bolesnica homozigot za mutaciju Y270D. Ova missense točkasta mutacija dovodi do negativnog naboja u visoko očuvanoj domeni eznima, u neposrednoj blizini katalitičkog mjesta (G 268). Mutacija je opisana u jednog bolesnika sa juvenilnom GM1 (Paschke i sur., 2001 ; 109:159-166), u kombinaciji s mutacijom T82M koja se nalazi kod adultnih bolesnika. Možemo zaključiti da je ova mutacija u homozigotnom obliku povezana s vrlo teškim oblikom GM1 gangliozidoze.

We report on a three and a half-year-old boy with multiple congenital anomaly-mental retardation syndrome characterized by profound sensorineural hearing loss, severe hypermetropia, omphalocele, bilateral ingunal hernia, hypoplasia of the corpus callosum, seizures and developmental delay. Distinctive facial features include wide forehead, high arched eyebrows, telecanthus, down-slanting palpebral fissures, high and prominent nasal bridge and submucosal cleft. High resolution karyotype and multicolor subtelomeric chromosome screening by fluorescent in situ hybridization showed normal results. A comprehensive review of syndromes with sensorineural deafness yielded no conclusive results, each being excluded on clinical or laboratory or cytogenetic grounds. Our patient shows some overlap with Donnai and Barrow and Malpuech syndromes. However, he is lacking some of the prominent symptoms of both conditions. Therefore we believe that his constellation of anomalies represents a distinct clinical entity.

The aim of this investigation was to define the frequency and types od acquired clonal chromosomal abnormalities in our group of childhood non-Hodgkin's lymphoma. Our investigation included 16 children, aged from 9 months to 15 years. Cytogenetic analysis of malignant cells was carried out at the time diagnosis was made, before initiating therapy. Slides were obtained from short-term culture of lymph node or bone marrow cells. Chromosome identification was carried out using G-banding method.Cytogenetic analysis revealed clonal chromosomal abnormalities in 11 (68.7%)out of 16 children. Chromosome instability and evidence of clonal evolution were observed in 3 patients. Pseudodiploid clone was observed in 4, hyperdiploid in 5 and hypotriploid in 2 out of 11 children with clonal chromosomal aberrations. This investigation revealed complex numerical and structural aberrations. The gains of some chromosome types were nonrandom and frequently affected chromosomes were 11, 14, 21 and X. Involvement of particular chromosome type in structural abnormalities was nonrandom too. The rearrangement involving chromosome No.1 and No. 14 were observed in 5 and 4 cases respectively. This investigation confirms variability of clonal chromosomal aberrations and cytogenetic heterogeneity of childhood non-Hodgkin lymphomas. Additional investigations are however, necessary to define more precisely the frequency and types of aberrations, and biological role of chromosomal regions in the development of NHL.

In this work we investigated the frequency of acquired clonal chromosomal abnormalities in our group of children with non-Hodgkin´s lymphoma. This study was carried out on a groupe of 16 children. Analysis was performed on slides obtained by direct or short-term culture of cells from lymph nodes, bone marrow and other affected tissue. GTG and CBG banding methodes were used for chromosome identification. Clonal chromosomal aberrations were observed in 12 patients (75%). Chromosome instability and evidence of clonal evolution were observed in 3 patients, pseudodiploid clone in 2, hyperdiploid in 8 and hypotriploid in 2 children with clonal chromosomal aberrations. Structural abnormalities were identified in 11 patients of which the most frequent was rearrangement involving chromosome number 1, observed in 6 patients.

Prikazujemo djevojčicu u dobi od 3 godine duplikacijom kratkog kraka kromosoma 8. Već po porodu uočene su dismorfične crte lica -dolihocefalija, visoko, prominentno čelo, široko razmaknute obrve, antimongoloidno položeni očni rasporci, velika usta, visoko nepce, lošije oblikovane uške i mala brada. Obradom se utvrdi postojanje ageneze korpus kalozuma, a daljim praćenjem umjereno razvojno zaostajanje. Citogenetička analiza uključujući i FISH pokazala je da djevojčica ima 46, XX, dup(8)(p21.3p23.1). Kariotip roditelja i starije sestre bio je uredan. Prikazana su klinička obilježja pojedinih parcijalnih duplikacija 8p te uspoređena s nalazom od naše bolesnice.

Genetic syndromes often have variable expression both regarding the presence or absence and the severity of specific malformations/traits. When the specific diagnostic test is lacking, it is often difficult to decide if a patient presents an atypical case of an already described rare syndrome or a distinct entity. We report on a three and a half-year old boy with a multiple congenital anomaly- mental retardation syndrome characterised by profound sensorineural hearing loss, severe hypermetropia, exomphalos, bilateral inguinal hernia, hypoplasia of the corpus callosum, seizures and developmental delay. He had dysmorphic facial features, including wide forehead, high arched eyebrows, telecanthus, down-slanting palpebral fissures, high and prominent nasal bridge and submucosal cleft. High resolution karyotype and multicolor subtelomeric chromosome screening by fluorescent in situ hybridisation yield normal results. The patient shows overlap with the two rare autosomal recessive disorders - Malpuech syndrome characterised by growth retardation, hypertelorism, facial clefting, hearing impairment, inguinal hernia and urogenital abnormalities and the syndrome descirbed by Donnai and Barrow (1993) consisting of diaphragmatic hernia, exomphalos, absent corpus callosum, hypertelorism, myopia and sensorineural deafness. However, the pattern of anomalies in our patient does not support convincingly any of the given diagnostic possibilities, which lead us to believe that this constellation of anomalies represents a distinct clinical entity.