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P08.3 A girl with 47 XXX karyotype mosaicism and aspartylglucosminuria
S66 is characterised by perseverations, articulation problems and limited vocabulary. He has a delay in fine and gross motor skills. The combination of relative microcephaly and developmental delay urges us to perform a cerebral MRI and complementary tests. Results: MRI images reveal multifocal subcortical lesions of 2−11 mm with enhanced diffusion and long relaxation time. There are lesions of 2−3 mm in the deep white matter close to the semioval center. Lateral ventricles are enlarged with slight colpocephaly. A karyotype reveals a 48XXYY chromosome variation. He obtains a harmonic SON-IQ of 69 which is equivalent with a delay of 1 year. Discussion: 48XXYY syndrome has an incidence of 1:18000 1:40000. Physical features include tall stature, hypertelorism, clinodactyly and dental problems. There are significant neurodevelopmental and behavioral problems. Brain MRI can show white matter abnormalities and enlarged ventricles. Common problems include asthma, congenital heart defects, radioulnar synostosis, inguinal hernia, cryptorchidism, hypergonadotropic hypogonadism, infertility and seizures. Additional features in adulthood include DVT, intention tremor and type II diabetes (1). Conclusion: In children with white matter abnormalities it is important to include a karyotype in the investigations. P08.3 A girl with 47 XXX karyotype mosaicism and aspartylglucosminuria H.J. Heiskala1 *, M. Koivusalo2 . 1 Clinic Group of Pediatric Neurology, Helsinki University Central Hospital, Finland, 2 School Health Care, Espoo Health Centre, Finland Background: to alert the clinicians search another diagnosis if the clinical picture does not fit to the first one. Aim: to describe the clinical course of a girl with two rare diseases. Methods: clinical follow-up with radiologic and cytogenetic studies. Results: In the cytogenetic studies performed during gestation and after birth a 46 XX (90%) / 47 XXX mosaicism (10%) was found. At the age of one year delayed psychomotor development was noticed and speech, occupational and physiotherapy were initiated. At the age of five years mild intellectual disability was diagnosed and the patient was referred to special education. During the school years her development was stagnating and she was referred again to outpatient clinic at the age of 11 years. Dysmorphic features (generous cheeks, periorbital fullness) characteristic to aspartylglucosaminuria (AGU) and clumsiness, abnormal speech and attention deficit were observed. High concentration of aspartylglucosamine was found in the urine sample and the MRI revealed typical findings of AGU including the dark thalami in T2-weighted images. The mutation analysis is pending. Conclusions: we describe a combination of conditions with prevalence estimate of one per 10 000 000 of live-born female infants [0.1% (XXX) times 0.01% (AGU in Finland, rarer elsewhere)]. The effect of the combination seems additive rather than synergistic since the major condition − AGU − dominates the picture.
Poster sessions P08.4 Large interstitial deletion of the short arm of chromosome 3 (3p12.3-p14.1): report of MITF haploinsufficiency non resulting in Waardenburg 2a phenotype A. Monier1 *, C. Vilain2 , B. Grisart3 , H. Dessy4 , A. Aeby5 , Universitaire des Enfants B. Dan1 . 1 Clinique de Neurologie, Hopital ˆ Reine Fabiola, Brussels, Belgium, 2 Unit´e de G´en´etique Clinique, Centre de G´en´etique Universit´e Libre de Bruxelles, Brussels, Belgium, 3 Centre de G´en´etique Humaine, Institut de Pathologie et de G´en´etique, Charleroi, Belgium, 4 Service de Cardiologie, Hopital ˆ Universitaire des Enfants Reine Fabiola, Brussels, Belgium, 5 Service de Neurop´ediatrie, Hopital Erasme, Brussels, Belgium ˆ We describe a 13 month-old girl, born with dysmorphic features (prominent forehead, epicanthus, hypertelorism, camptodactyly) and short stature after a pregnancy marked by polyhydramnios and enlargement of the IVth ventricle. Postnatal karyotype and CGH-array revealed a large interstitial deletion (10.965 Mb) on 3p12.3-p14.1, involving many genes, including MITF. Mutations of MITF result in different phenotypes, depending upon the extent, the type and the position. Haploinsufficiency results in Waardenburg type 2a syndrome (patchy pigmental abnormalities, irian heterochromy and variable hearing loss) whereas mutations of the basic portion of MITF are responsible for Tietz syndrome (generalized hypopigmentation and profound bilateral congenital deafness). Our patient developed mild developmental delay, profound bilateral deafness, patent ductus arteriosus and interauricular communication. Irian heterochromy was present, with no pigmentary abnormalities. Brain MRI at 12 months confirmed mild enlargement of the IVth ventricle with coarse corpus callosum. Very few patients are described with interstitial deletion of the short arm of chromosome 3, all (including our patient) with different breakpoints. All presented developmental delay and various congenital abnormalities. Surprisingly, MITF haploinsufficiency in our patient results in irian heterochromy and profound hearing loss in the absence of pigmental abnormalities, not matching with typical Waardenburg 2a syndrome. Mutation on the residual allele as well as loss of function of other genes within the deleted fragment could play a role in the phenotype. Further descriptions are needed to better characterize a 3p interstitial deletion syndrome and offer our patients optimal assessment and management. P08.5 Intractable myoclonic epilepsy, mental retardation and dysmorphic features in a boy with chromosomal aberration: 46XY. ish der(15)t(X;15)(p22.; q26.3)dn I. Ðakovic´ 1 *, V. Mejaˇski Boˇsnjak1 , V. Tokic´ 2 , G. Milihram3 . Clinical Hospital “Sisters of mercy”, Children’s Hospital Zagreb, Department of pediatrics, Division of neuropediatrics, Klai´ceva 16, 10000 Zagreb, Croatia, 2 Clinical Hospital “Sisters of mercy”, Children’s Hospital Zagreb, Department of pediatrics, Klai´ceva 16, 10000 Zagreb, Croatia, 3 General Hospital “Varazdin”, Department ˇ of pediatrics, Ivana Meˇstrovi´ca bb, 42000 Varazdin, Croatia ˇ 1
Background: Mental retardation affects 2−3% of general population and genetic cause can be detected in around 5% of patients. Many of these patients also suffer from epilepsy. Aim of the study: We present 13 years old patient with de novo chromosomal aberation characterized by addition of Xp chromosome (partial trisomy) to terminal part of 15q chromosome associated with intractable myoclonic epilepsy, mental retardation and dysmorphic features. Methods: The boy is third child of healthy parents and has two healthy siblings. At the age of 6 months psychomotor retardation was noticed. He revealed numerous dysmorphic features: down-slanted palpebral fissures, hypertelorism,
Poster sessions P08.4 Large interstitial deletion of the short arm of chromosome 3 (3p12.3-p14.1): report of MITF haploinsufficiency non resulting in Waardenburg 2a phenotype A. Monier1 *, C. Vilain2 , B. Grisart3 , H. Dessy4 , A. Aeby5 , Universitaire des Enfants B. Dan1 . 1 Clinique de Neurologie, Hopital ˆ Reine Fabiola, Brussels, Belgium, 2 Unit´e de G´en´etique Clinique, Centre de G´en´etique Universit´e Libre de Bruxelles, Brussels, Belgium, 3 Centre de G´en´etique Humaine, Institut de Pathologie et de G´en´etique, Charleroi, Belgium, 4 Service de Cardiologie, Hopital ˆ Universitaire des Enfants Reine Fabiola, Brussels, Belgium, 5 Service de Neurop´ediatrie, Hopital Erasme, Brussels, Belgium ˆ We describe a 13 month-old girl, born with dysmorphic features (prominent forehead, epicanthus, hypertelorism, camptodactyly) and short stature after a pregnancy marked by polyhydramnios and enlargement of the IVth ventricle. Postnatal karyotype and CGH-array revealed a large interstitial deletion (10.965 Mb) on 3p12.3-p14.1, involving many genes, including MITF. Mutations of MITF result in different phenotypes, depending upon the extent, the type and the position. Haploinsufficiency results in Waardenburg type 2a syndrome (patchy pigmental abnormalities, irian heterochromy and variable hearing loss) whereas mutations of the basic portion of MITF are responsible for Tietz syndrome (generalized hypopigmentation and profound bilateral congenital deafness). Our patient developed mild developmental delay, profound bilateral deafness, patent ductus arteriosus and interauricular communication. Irian heterochromy was present, with no pigmentary abnormalities. Brain MRI at 12 months confirmed mild enlargement of the IVth ventricle with coarse corpus callosum. Very few patients are described with interstitial deletion of the short arm of chromosome 3, all (including our patient) with different breakpoints. All presented developmental delay and various congenital abnormalities. Surprisingly, MITF haploinsufficiency in our patient results in irian heterochromy and profound hearing loss in the absence of pigmental abnormalities, not matching with typical Waardenburg 2a syndrome. Mutation on the residual allele as well as loss of function of other genes within the deleted fragment could play a role in the phenotype. Further descriptions are needed to better characterize a 3p interstitial deletion syndrome and offer our patients optimal assessment and management. P08.5 Intractable myoclonic epilepsy, mental retardation and dysmorphic features in a boy with chromosomal aberration: 46XY. ish der(15)t(X;15)(p22.; q26.3)dn I. Ðakovic´ 1 *, V. Mejaˇski Boˇsnjak1 , V. Tokic´ 2 , G. Milihram3 . Clinical Hospital “Sisters of mercy”, Children’s Hospital Zagreb, Department of pediatrics, Division of neuropediatrics, Klai´ceva 16, 10000 Zagreb, Croatia, 2 Clinical Hospital “Sisters of mercy”, Children’s Hospital Zagreb, Department of pediatrics, Klai´ceva 16, 10000 Zagreb, Croatia, 3 General Hospital “Varazdin”, Department ˇ of pediatrics, Ivana Meˇstrovi´ca bb, 42000 Varazdin, Croatia ˇ 1
Background: Mental retardation affects 2−3% of general population and genetic cause can be detected in around 5% of patients. Many of these patients also suffer from epilepsy. Aim of the study: We present 13 years old patient with de novo chromosomal aberation characterized by addition of Xp chromosome (partial trisomy) to terminal part of 15q chromosome associated with intractable myoclonic epilepsy, mental retardation and dysmorphic features. Methods: The boy is third child of healthy parents and has two healthy siblings. At the age of 6 months psychomotor retardation was noticed. He revealed numerous dysmorphic features: down-slanted palpebral fissures, hypertelorism,