the overall incidence of craniopharyngioma in the period of 1989-2008 in Macedonia was 1.43 per 1 000 000 person-years. Subtotal resection and systematic irradiation showed good life quality of survivors.

Hyper-IgE syndromes and chronic mucocutaneous candidiasis constitute rare primary immunodeficiency syndromes with an overlapping clinical phenotype. In recent years, a growing number of underlying genetic defects have been identified. To characterize the underlying genetic defects in a large international cohort of 275 patients, of whom 211 had been clinically diagnosed with hyper-IgE syndrome and 64 with chronic mucocutaneous candidiasis, targeted panel sequencing was performed, relying on Agilent HaloPlex and Illumina MiSeq technologies. The targeted panel sequencing approach allowed us to identify 87 (32 novel and 55 previously described) mutations in 78 patients, which generated a diagnostic success rate of 28.4%. Specifically, mutations in DOCK8 (26 patients), STAT3 (21), STAT1 (15), CARD9 (6), AIRE (3), IL17RA (2), SPINK5 (3), ZNF341 (2), CARMIL2/RLTPR (1), IL12RB1 (1), and WAS (1) have been detected. The most common clinical findings in this cohort were elevated IgE (81.5%), eczema (71.7%), and eosinophilia (62.9%). Regarding infections, 54.7% of patients had a history of radiologically proven pneumonia, and 28.3% have had other serious infections. History of fungal infection was noted in 53% of cases and skin abscesses in 52.9%. Skeletal or dental abnormalities were observed in 46.2% of patients with a characteristic face being the most commonly reported feature (23.1%), followed by retained primary teeth in 18.9% of patients. Targeted panel sequencing provides a cost-effective first-line genetic screening method which allows for the identification of mutations also in patients with atypical clinical presentations and should be routinely implemented in referral centers.

Hypomethylation of the imprinting control region 1 (ICR1) at the IGF2/H19 locus on 11p15 is linked to Silver-Russell syndrome (SRS) and/or hemihypertrophy. This SRS patient was born in term with weight of 3500 g (50 percentile) and length 48 cm (1 SD below the mean). He was first noticed at the age of 10 years for short stature (114.5 cm, -3.85 SD), relatively normal head circumference, a classic facial phenotype, hemihypertrophy (2.5 cm thinner left arm and leg in comparison to the right, asymmetric face), moderate clinodactyly and striking thinness (BMI of 15.3). At the age of 30, the body asymmetry ameliorated (1 cm thinner left arm and leg than the right), and BMI normalized (20.5 cm). Methylation analysis was performed by bisulphate treatment of DNA samples, radiolabelled PCR amplification, and digestion of the PCR products using restriction enzymes. The patient had normomethylation, and in addition hypopituitarism, with low levels of growth hormone (GH) (provocative testing before the start and after termination of GH treatment), thyroxin, TSH, FSH, LH and testosterone. The GH was given for six years, growth response was satisfactory and he reached an adult height of 166 cm. This is a first report of hypopituitarism in a patient with SRS without H19 hypomethylation. It seems that the lack of hypomethylation in this hypopituitary SRS patient is responsible, at least partly, for the favourable final adult height under GH treatment.

The majority of congenital diaphragmatic hernia (CDH) are diagnosed antenatally, immediately after birth or in the neonatal period. We report case of 4-year-old child who presented with recurrent wheezing and was diagnosed to have late presenting CDH.A 4-year-old girl was admitted to the hospital with a 5-days history of increasing shortness of breath and cough. The child had normal bird history and has enjoyed relatively good health till 3 years of age. Her medical history over the last year revealed that she had 4 episodes of wheezing variously treated with inhaled bronchodilators, steroids and antibiotics.On physical examination she was in mild respiratory distress with bilateral wheezing. The x-ray showed an unusual appearance of the chest with air-filled bowel loops. A barium X-ray examination of the gastrointestinal tract confirmed the diagnosis of CDH. The hernial contents were reduced back into the abdominal cavity and surgical repair of the diaphragmatic defect was done.Late presenting CDH can be misdiagnosed and lead to delayed treatment. It should be suspected in children presenting with recurrent respiratory symptoms.When the diagnosis is confirmed, the treatment of choice is surgical intervention. Clinical awareness, early diagnosis and operative treatment can lead to good outcomes.

Tay-Sachs diseases are group of rare autosomal recessive lysosomal disorders, GM2gangliozidoses. They are progressive neurodegenerative diseases, caused by a mutation in the enzyme β-hexosaminidaseA. Depending on the time of presentation of symptoms, there are three forms: infantile, juvenile and adult. We present a 8 year old patient, who is presented at the age of 4 with progressive deterioration in psychomotor and speech skills, pyramidal symptoms, ataxia and muscle weakness. The EEG showed bihemispheric fast spike waves and the MRI showed no findings of organic disease. Finally amolecular genetic testing was made, which proved the diagnosis of juvenile form of Tay-Sachs disease. It was determined that the patient is a compound heterozygote, with two different mutations in the alleles of the HEXA gene, one inherited from the mother and the other one from the father.The juvenile Tay-Sachs disease is characterized with onset between the age of 2 to 10 years old. Clinically it is presented with muscle weakness, incoordination, ataxia, dysarthria, dysphagia and progressive spasticity. It progresses to development of dementia, convulsions, blindness and vegetative state with decerebrate rigidity and death by the age of 15. It is inherited autosomal recessive with one mutation present on both alleles of the HEXA gene. Treatment options for Tay-Sachs disease currently are only symptomatic and supportive. There are ongoing researches for curative treatments for Tay-Sachs, like enzyme replacement, chaperone, substrate reduction and gene therapy.