Neurodevelopmental Retardation Research Articles

Predictive Value of Neurodevelopmental Outcome and Serum Tau Protein Level in Neonates with Hypoxic Ischemic Encephalopathy.

Tau protein is s specific protein expressed by neurons in the central nervous system. Elevated serum Tau protein is associated with many diseases of the central nervous system. The serum Tau protein level in neonates with hypoxic ischemic encephalopathy (HIE) is still poorly understood. Forty-one human neonates with HIE and thirty-five healthy neonates (control group) within 24 hours after birth were studied. Tau protein in serum was detected by enzyme-linked immunosorbent assay. Neurological outcome was assessed at 9 months of age according to the Gesell developmental scale. Tau protein in serum was significantly higher in the HIE group than in the control group (p < 0.01), in neonates with severe HIE than neonates with moderate HIE (p < 0.01), and in infants with neurodevelopmental retardation compared with those with normal neurodevelopment (p < 0.01). The result of this study showed an obvious negative correlation between the serum Tau protein level and development quotients of neonates with HIE (rs = -0.6172, p < 0.01). Receiver operator characteristic curve analysis showed that Tau protein (cutoff value 933.04 pg/mL) was a predictor of neurodevelopmental retardation outcome (AUC value = 0.860 (95% CI: 0.736 - 0.983, p < 0.01), sensitivity 100%, specificity 70.8%). Serum Tau protein level within 24 hours after birth can be used as a marker for the early diagnosis of neonatal HIE and predicting neurodevelopmental outcomes.

Evaluation of short-term neurodevelopmental outcomes in the premature patients with periventricular-intraventricular hemorrhage

Despite the significant advancements in perinatal care, it is not clear whether or not the neurodevelopmental outcome in children with intraventricular hemorrhage (IVH) has improved in parallel with the declining incidence of periventricular- IVH. In this study, we aimed to assess the periventricular-IVH-induced mortality and morbidity rates, as well as the short-term neurodevelopmental outcomes in premature infants. Two hundred and sixty five patients who were admitted between September 2005 and May 2006 were investigated for periventricular-IVH. Sixty-six patients with periventricular-IVH were compared with 66 premature infants who were not associated with hemorrhage. Of the periventricular-IVH diagnosed premature infants, 59% were born at or before week 32, 61% had a body weight below 1500 g, and 24.9% had hemorrhage. In cases with periventricular-IVH, the rates of premature retinopathy and periventricular leukomalacia were significantly high ( P 0.05) while the relation between periventricular-IVH and neuromotor developmental retardation was significant ( P< 0.05). The outcome was poorer as the grade of bleeding increased ( P< 0.05). As a conclusion, regardless of risk factors, periventricular-IVH is an important early indicator of neurodevelopmental retardation, and those cases having such condition should be always assessed with a neurodevelopmental evaluation. The detection of neurodevelopmental retardation in short term with appropriate educational strategy could be beneficial for long-term outcome.

Evaluation of growth in very low birth weight preterm babies.

The aim of this study was to evaluate physical growth of very low birth weight (VLBW) preterm babies at a mean age of three years and to investigate the factors which affected growth. The factors including maternal problems, prenatal problems, early neonatal problems, nutrition, familial socioeconomical status and presence of chronic disease which affected catch-up growth in terms of height and weight in VLBW infants followed up in the neonatal intensive care unit (NICU) of our hospital were examined. The target height formula was used in assessment of growht in height and the contribution of genetic properties was investigated. The points of the subjects on the growth curve were plotted according to the Percentile Curve of the Turkish Children prepared by Neyzi et al. The states of the subjects with and without intrauterine growth retardation (were compared. The study was intitiated after obtaining approval from the ethics committeee of our hospital (100/25.10.2005). One hundred and seventeen preterm babies (57 females and 60 males) with a mean adjusted age of 35.8±2.39 80 of whom were appropriate for gestational age (AGA), 28 of whom were symmetrical (small gestational age) SGA and 9 of whom were asymmetrical SGA were included in the study. The mean gestational age (GA) was found to be 31±2.16 weeks and the mean birth weight (BW) was found to be 1271±226 g. The mean current height was found to be 92.06±4.90 cm. The mean weight was found to be 12.98±1.94 kg. The mean target height was calculated to be 163.66±8.1 cm (157.20 cm for the girls and 170.20 cm for the boys). It was found that 15 preterm babies (12.8%) could not achieve the target height (girls: 6%, boys: 6.8%). The risk factors related with failure to achieve target height were found to include ventilator treatment, presence of chronic disease, advanced stage intracranial bleeding (ICB), posthemorrhagic hydrocephalus, absence of breastfeeding, failure to sit at the table with the family and malnutrition. The maternal age, early rupture of membranes (PROM), preeclampsia, smoking, early neonatal problems, gender, being AGA and SGA, gestational age, birth weight and socioeconomical level were statistically insignificant in terms of achieving target height (p>0.05). If very low birth weight preterm babies have no chronic disease and condition leading to neurodevelopmental retardation and if they are breastfed early and continuously (0-24 months), they can achieve catch-up growth similar to term babies. In examination of growth in terms of height, using target height may be more appropriate to shown the genetic potential.

B12 Vitamini Eksikliğine İkincil Hemoliz Bulguları Olan Yaşamı Tehdit Eden Anemi, Trombositopeni ve Beyin Atrofisi

Megaloblastic anemia due to vitamin B12 deficiency is rare in infancy. It usually occurs in exclusively breast-fed infants born to vitamin B12-deficient mothers. We report a one-year-old female infant with initial diagnosis of leukemia who was found severely vitamin B12-deficient secondary to maternal deficiency. She had marked neurodevelopmental retardation, and presented with life-threatening anemia, findings of hemolysis, thrombocytopenia and cerebral atrophy on magnetic resonance imaging.

Congenital Cataract Facial Dysmorphism Neuropathy Syndrome: Differential Diagnosis of Bilateral Congenital Cataract

When congenital cataract is present, the differential diagnosis comprises infectiological, metabolic, and genetic disorders. A definitive classification can often only be made when additional symptoms develop. We present a girl of Roma origin with bilateral congenital cataract and progressive neurodevelopmental retardation who was diagnosed with Congenital Cataract, Facial Dysmorphism, and Neuropathy (CCFDN) syndrome. This autosomal recessive disorder is a clinical differential diagnosis of Marinesco-Sjögren syndrome. It has been diagnosed in Roma and Sinti families only and represents one of the most frequent causes of congenital cataract in this ethnic group. It should therefore be sought out specifically by genetic testing of the CTDP1 gene when the adequate clinical picture is present.

Early-onset diabetes mellitus and neurodevelopmental retardation: the first Greek case of Wolcott-Rallison syndrome

Wolcott-Rallison syndrome (WRS) is a very rare genetic disorder, which is transmitted by autosomal recessive inheritance and results from mutations in the gene encoding the eukaryotic initiation factor 2-α kinase-3 (EIF2AK3). The cardinal features of the syndrome include early-onset insulin-dependent diabetes mellitus, multiple epiphyseal dysplasia, and growth retardation. We present the case of a 13-year-old Greek boy with a known history of infancy-onset diabetes mellitus and was found to have WRS at the age of 4 years. He presented with acute liver and renal insufficiency in addition to skeletal dysplasia and neurodevelopmental retardation. The clinical suspicion of WRS was confirmed by molecular analysis of the EIF2AK3 gene. The patient was found to be a compound heterozygote with two different novel mutations (c.2776C>T, p.R902X and c.3038A>G, p.Y989C). The current patient is one of the longer survivors.

Neurodevelopmental retardation, as assessed clinically and with magnetoencephalography and electroencephalography, associated with perinatal dioxin exposure

In 1980s Western Europe, human perinatal exposure to background levels of dioxins was rather high. We therefore evaluated the neurodevelopment of our cohort during the prepubertal period and in adolescence.At prepubertal age (7–12years) 41 children were tested. Both neuromotor functioning and psychological testing were performed (Dutch version of the Wechsler Intelligence Scale for Children (WISC-R) and the Dutch version of the Child Behavior Checklist for ages 4–18years (CBCL 4–18) and the Teacher Report Form (TRF)). Neurophysiological tests were performed using magnetoencephalography and electroencephalography.In adolescence (14–18years) the behavior of 33 children was studied again (CBCL and TRF). And the levels of dioxins and dioxin-like PCBs (dl-PCBs) were measured in serum. ResultsAt prepubertal age no association was found between perinatal dioxin exposure and verbal, performal and total IQ or with the Touwen's test for neuromotor development. There were behavioral problems associated with both prenatal and postnatal dioxin exposure. In adolescence there were problems associated with the current dioxin levels and dioxin-like-PCBs.Neurophysiological tests revealed clear negative dysfunction. An increase in latency time after a motion stimulus (N2b) of 13ms (= a delay of 10%) is associated with the higher prenatal dioxin exposure. A similar delay was measured in testing cognitive ability by analyzing the odd ball measurements, N200 and P300, together with an amplitude decrease of 12 %. The delay is indicative of a defective myelinisation and the decrease in amplitude of a loss of neurons. ConclusionWe found effects on behavior in association with the perinatal dioxin exposure and in adolescence in association with the current dioxin levels.Neurophysiological testing is instrumental in the detection of effects of perinatal background levels of chemicals on brain development in normal, healthy children. The clinical, neurological and psychological tests commonly used are not sensitive enough to detect important effects.

Medical Treatment in Childhood Epilepsies

Summary The majority of epileptic seizures are controlled with antiepileptic drugs (AEDs). Whether or not to start treatment following an initial unprovoked seizure should be decided on an individualized basis; and, the risk of seizure recurrence versus possible side-effects and social conse quences of chronic AED treatment should be evaluated. Main risk factors for seizure recurrence can be summarized as the presence of focal seizure types, organic brain lesion, focal neurologic abnormality, previous neurodevelopmental retardation, specific EEG abnormality and positive family history of epilepsy. The AED chosen for initial therapy should be one that is highly effective for a particular seizure type and epilepsy syndrome, as also, that is safe and well tolerated. Monotherapy is the goal in epilepsy treatment. If the first two monotherapies fail, combinations of AEDs should be tried. Withdrawal of AED therapy should be considered in most children after two years without seizures. AEDs should be tapered slowly rather than halted abruptly.

A new small supernumerary marker chromosome involving 14pter → q12 in a child with severe neurodevelopmental retardation: Case report and literature review

Unstable, gene-rich pericentric regions have been associated with various structural aberrations including small supernumerary marker chromosomes (sSMCs). We hereby report on a new sSMC derived from chromosome 14, generating trisomy 14pter→q12 in a child with severe neurodevelopmental delay. The patient featured facial dysmorphism, generalized hypotonia, transverse palmar creases, structural brain abnormality, and severe cognitive and motor impairment. Literature review indicated this to be a unique case of sSMC 14 which was only composed of pter→q12, and the phenotype secondary to duplications of the similar region partially overlaps with the phenotype reported in this study. The genetic analysis on our case helps to better delineate karyotype–phenotype correlations between proximal trisomy 14 and associated clinical phenomena, and we also propose that the involved chromosomal regions may contain dosage-sensitive genes which are important for the development.

A novel MT-CO2 m.8249G > A pathogenic variation and the MT-TW m.5521G > A mutation in patients with mitochondrial myopathy

Mitochondrial DNA (mtDNA) defects were known to be associated with a large spectrum of human diseases and patients might present wide range of clinical features with various combinations. Mutations in mitochondrial tRNAs, rRNAs and protein-coding genes or large-scale rearrangements have been implicated in several cytopathies. Mitochondrial myopathies, usually maternally inherited group of neuromuscular diseases caused by mitochondrial dysfunction occurring before the age of 20 years and often begin with exercise intolerance, muscle weakness and neurodevelopmental retardation. We studied the mtDNA in three Tunisian patients with mitochondrial myopathy. The mutational analysis screening revealed the presence of two mitochondrial mutations: the m.5521G > A mutation in the D-stem region of the tRNATrp gene which could lead to a disruption of the secondary structure of this tRNA and affect the tRNA–ribosome interaction with a consequent decrease in the rate of synthesis of mitochondrial proteins. The second mutation is the m.8249G > A (p.G222R) variation in the MT-CO2 gene which may affect the electrons transfer from cytochrome c to the bimetallic center of the catalytic subunit I.

Distinct neurological features in a patient with Schinzel–Giedion syndrome caused by a recurrent SETBP1 mutation

Schinzel-Giedion syndrome (SGS) is a rare multiple congenital malformation syndrome defined by characteristic facial features, profound developmental delay, severe growth failure, and multiple congenital anomalies. Most individuals affected by SGS die in early childhood mainly because of progressive neurodegeneration and respiratory failure. The causative gene of SGS, SETBP1, was identified, but there are few reports of SGS with molecular confirmation worldwide. In this study, we present a 10-month-old boy presenting with SGS complicated by epilepsy and profound developmental delay. Typical facial features, multiple anomalies, and associated neurological findings suggested a clinical diagnosis of SGS. Unusually in our patient, generalized tonic seizure occurred and has been controlled well by combined antiepileptic therapy during 7 months of follow-up. Electroencephalography findings were compatible with partial seizures, and ventriculomegaly, thinning of the corpus callosum, and delayed myelination were identified on brain MR images. SETBP1 mutational analysis revealed the presence of a recurrent mutation, p.Gly870Ser. Thus, the diagnosis of our patient was molecularly confirmed as SGS. Although this syndrome is extremely rare, it is important to consider SGS in the differential diagnosis of infantile-onset epilepsy with progressive neurodevelopmental retardation, especially in patients with multiple anomalies and facial dysmorphism.

Bardet Biedel Syndrome: A Very Rare Entity in India

Bardet Biedel Syndrome (BBS) is a rare autosomal recessive disease which is characterized by obesity, retinitis pigmentosa, polydactyly, neuro-developmental retardation and renal defects amongst others. It is a genetically heterogeneous ciliopathic disorder with inter and intra familial variations. Very few cases have been reported from India. We are reporting here a case of an adolescent girl who was diagnosed at the age of 16, with additional features of insulin resistance and non-alcoholic fatty liver disease. A review of recent literature and a short discussion on the care and management of this uncommon condition follow.

Correlación de la morfometría por resonancia magnética con los hallazgos clínicos y electroencefalográficos de pacientes con diagnóstico de ulegiria y epilepsia

Ulegyria is a cortical lesion affecting neighbouring vascular zones, which gives the convolutions a mushroom-like appearance. It is an important cause of occipital epilepsy. AIM. To correlate patients diagnosed clinically, electrically and morphometrically with ulegyria and epilepsy by comparing the thickness of the cortex in the zones affected by ulegyria with the normal cortical thickness reported in the literature and the average cortical thickness of healthy subjects. Ten patients with ulegyria confirmed by magnetic resonance imaging were included in the study; all of them were submitted to a clinical interview, an electroencephalographic study and cortical morphometric analysis based on volumetric T1 sequences. Findings included a predominance in males, neurodevelopmental retardation and epilepsy. Ulegyria was mainly parietooccipital, frequently bilateral, with statistically significant thinning of the cortical thickness in the site of the lesion and an increase in the thickness of the cortex in the areas surrounding the lesion. We report on a series of patients with ulegyria with characteristics similar to those existing in the literature and by means of morphometry we detected an increase in the thickness of the cortex around the areas affected by ulegyria. These findings could point to the presence of adaptive neuroplasticity in the neurons that surround the scar tissue or they may be the result of mechanical changes of normal tissue in response to the loss of volume of the ulegyria-affected area, although these data need to be replicated in a study with a greater number of patients.

Cranial magnetic resonance imaging findings of nutritional Vitamin B12 deficiency in 15 hypotonic infants

BackgroundNutritional vitamin B12 deficieny is common among infants in the developing and underdeveloped countries. There is limited information concerning neuroimaging findings in infants with vitamin B12 deficiency in the literature. AimsThe aim of this study is to evaluate the cranial magnetic resonance imaging (MRI) changes and clinical characteristics of hypotonic infants due to vitamin B12 deficiency. Materials and methods: A total of 15 infants with neuroradiologic investigations were diagnosed with nutritional B12 vitamin deficiency. Cranial MRI was performed on all infants. ResultsFive infants were female (33%) and the mean age of infants was 12.3 ± 5.5 months. Hypotonia and neurodevelopmental retardation were present in all patients. MRI demonstrated thinning of the corpus callosum in 6 (40%), cortical atrophy in 5 (33.3%), large sylvian fissures in 5 (33.3%), ventricular dilatation in 3 (20%), asymetric large lateral ventricle in 2 (13.3%) and delayed in myelination in 2 (13.3%) patients. Four infants had normal MRI findings. ConclusionBecause of the importance of vitamin B12 in the development of the brain, MRI findings may be detected and useful in infants with vitamin B12 deficiency.

Neurological presentations of nutritional vitamin B12 deficiency in 42 breastfed infants in Southeast Turkey

Nutritional vitamin B12 deficiency is common in developing and underdeveloped countries and has a wide variety of neurological presentations. The aim of this study was to evaluate the neurological characteristics and laboratory results of infants with vitamin B12 deficiency. Materials and methods: A total of 42 infants were included in this study. All patients were evaluated for clinical, physical, and neurological abnormalities, and an attempt was made to obtain short-term neurologic follow-up. Results: Of 42 patients, 24 (57%) were boys and 18 (43%) were girls. The average age at diagnosis was 13.04 ± 5.68 months. Most of these infants were breastfed only and born from mothers with inadequate animal-derived protein consumption. Hypotonia (100%), anorexia (92.8%), neurodevelopmental (85.7%), and social (80.9%) retardation were the most present symptoms in all infants. Conclusion: Severe neurological and hematological findings may be found in children with vitamin B12 deficiency. Early diagnosis and treatment is crucial in cases of hematological complications and neurologic impairment. Neurologic impairment may be irreversible if the diagnosis is delayed beyond 12 months. We think that dietary management, such as nutritional support with vitamin B12 for the mothers during pregnancy and complementary food for infants, may prevent the neurological deficits and neurodevelopmental retardation.

Disorders of prosencephalic development

Abnormal ventral induction may result in disorders of formation, cleavage, and midline development of prosencephalic structures. Holoprosencephaly is a developmental field defect of impaired cleavage of prosencephalon. The most widely accepted classification of holoprosencephaly recognizes three major varieties: the alobar, semilobar and lobar types, according to the severity of the malformation. The brain malformations, characterized by the fusion of the cerebral hemisphere along the midline are commonly associated with facial anomalies. Corpus callosum agenesis and septo-optic dysplasia are disorders of prosencephalic midline development, and usually have less severe presentations but still, affected subjects may suffer from neurodevelopmental retardation, and/or endocrinologic and visual disorders. In this article we report an up-to-date of pathogenesis, prenatal sonographic findings, differential diagnosis and prognosis of the aforementioned anomalies.

SSADH deficiency leads to elevated extracellular GABA levels and increased GABAergic neurotransmission in the mouse cerebral cortex.

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an inherited disorder in which patients display neurodevelopmental retardation, ataxia, and epileptic seizures. The recently engineered SSADH knock-out (KO) mouse models the severe form of the human disorder. The SSADH enzyme participates in the breakdown of the inhibitory neurotransmitter GABA, and studies have shown increases in brain GABA and downregulation of GABA(A) receptor beta(2) subunits in the cerebral cortex of these mice. Here, we used brain slice electrophysiology to investigate the alterations in GABA neurotransmission in SSADH KO mouse cortex. In layer 2/3 pyramidal cells, spontaneous inhibitory postsynaptic currents (IPSCs), reflecting activity of GABAergic synaptic contacts, were normal in SSADH KO mice. Also, IPSCs evoked by electrical single-axon stimulation in KO mice were normal. In contrast, tonic inhibition mediated by presumed extrasynaptic GABA(A) receptors was strongly increased, indicating significantly raised extracellular GABA levels. The excessive cortical GABAergic neurotransmission may participate in the seizure activity in SSADH deficiency.

Neurodevelopmental Implications of Congenital Heart Disease

After completing this article, readers should be able to: 1. Describe the causes of central nervous system injury for infants who have congenital heart disease. 2. List genetic causes of congenital heart disease associated with developmental delay. 3. Identify potential intraoperative mechanisms for neurologic injury for infants who have congenital heart disease. 4. Identify risk factors for adverse neurodevelopmental outcomes for infants who have congenital heart disease. 5. Describe which long-term developmental deficits are common among children who have congenital heart disease. Among the more than 40,000 infants born with congenital heart disease (CHD) annually in the United States, one third require surgery during the first year after birth. (1) As advances in prenatal diagnosis, perioperative management, and surgical techniques have contributed to reduce rates of mortality, attention has shifted toward the neurodevelopmental morbidity among the growing cohort of survivors. Supportive surgical techniques, including cardiopulmonary bypass and deep hypothermic cardiac arrest (DHCA), have been a focus of outcome investigation, but mounting evidence suggests that multiple risk factors contribute significantly toward neurodevelopmental impairment. Long-term deficits in domains of cognition, attention, and neuromotor functioning among patients likely reflect the cumulative impact of features present before, during, and after surgical intervention. ### Genetic Implications Genetic abnormalities and syndromes are present in many infants who have CHD and may be associated with neurodevelopmental delay (Table 1). Trisomy 21 affects 1 in 660 newborns; 40% of affected infants have CHD. Neurodevelopmental deficits, including hypotonia and mental retardation, are common among all patients who have trisomy 21. (5)(6) Among infants who have conotruncal defects, 18% have been found to have a microdeletion on chromosome 22. (17) Evaluation of children who have the 22q11 deletion, present in most infants who have velocardiofacial and DiGeorge syndromes, has revealed a unique profile of cognitive deficits. Impairments in visuospatial memory, attention, and language are common, and …

Prenatal diagnostic indicators of paternal uniparental disomy 14

To present clinical findings of a child with paternal uniparental isodisomy 14 (pat UPD14) focusing on relevant prenatal characteristics. Ultrasonography at 23 weeks of gestation of a 37-year-old multigravid woman revealed a fetus with polyhydramnios, small thorax, and short, distinctively angled ribs. Fetal karyotype was 46,XY. The child was born spontaneously at 35 weeks with poor neonatal adaptation. From birth, he presented with severe respiratory insufficiency due to severe thoracic malformation. Clinical examination revealed a small, bell-shaped thorax, redundant lax skin, mild contractures of the fingers and dysmorphic facial features. Chest X rays showed short, abnormally curved ribs that suggested the possibility of pat UPD14, which was confirmed by molecular analysis. Pat UPD14 is associated with a distinct clinical phenotype. Prognosis is poor because of severe respiratory insufficiency and neurodevelopmental retardation. Our report confirms salient postnatal signs of previous descriptions, especially the characteristic radiological abnormalities with ribs showing a 'coat-hanger' configuration. Retrospective fetal ultrasound of our case allowed the identification of this pathognomonic feature prenatally, which makes it possible to consider pat UPD14 at routine prenatal sonography, in particular in combination with a small bell-shaped thorax and polyhydramnios.

Chromosome 22q11.2 deletion syndrome: an underestimated cause of neuropsychiatric impairment in adolescence

Sirs: Chromosome 22q11.2 deletion syndrome is a common multiple malformation syndrome estimated to affect between 1 in 4000 and 1 in 5000 individuals [1]. With the advent of molecular genetics a 3-Mb microdeletion within 22q11 was found to underlie a heterogeneous group of disorders with overlapping features, such as Di George and velocardiofacial syndrome [2, 3]. The phenotype of the disorder has expanded considerably within the last few years, whereas the clinical features vary significantly among affected individuals [4]. However, cardiovascular defects, immunological deficits, neurodevelopmental retardation, craniofacial abnormalities and hypocalcemia are recognised as the major and most frequent manifestations of the syndrome [5]. A 17-year-old boy presented with a gradual cognitive and behavioral decline over the last 18 months. The symptom onset coincided with a febrile gastrointestinal tract infection and was initially characterized by anxiety, altered sleep pattern, bizarre statements and actions and lack of initiative. The patient exhibited bland, and at times inappropriate affect, whereas his thought and behavior were mildly but progressively disorganised. The patient became eventually socially withdrawn and was unable to attend to his school activities. However, no hallucinations or delusions were present. He showed poor response to neuroleptic medication and remained withdrawn with psychomotor retardation and poverty of speech. His past medical history was significant for non-febrile neonatal seizures, which were attributed to hypocalcemia. At that time, he was diagnosed as having hypoparathyroidism, whereas further investigation showed thymic hypoplasia with marginally reduced T-cell numbers. However, no chromosomal abnormality was found on karyotyping. Developmental milestones were also delayed; he began to walk at 17 months and first combined single words into full sentences around 48 months of age. The patient had attended regular school classes, but his overall school performance had always been poor with prominent deficits in visuo-spatial abilities and executive functioning. He was also diagnosed as having bilateral stenosis of the external auditory canal, and an inguinal hernia had been repaired at 3 months of age. Moreover, the patient had an episode of septicemia due to pneumococcal infection at the age of 13. His family history was unremarkable, apart from a diagnosis of schizophrenia in a paternal great uncle. The patient was admitted and evaluated mainly by the neurology services. On examination, he was noted to have slightly dysmorphic facial features consisting of broad nasal root, malar flattening and relative retrognathia. His speech was hypernasal without overt cleft palate, but the general neurological and physical examination were otherwise unremarkable. Neuropsychological assessment revealed moderate deficits on verbal, as well as non-verbal reasoning tests, whereas the patient’s visual perceptual skills and memory appeared to be mildly impaired. The prominent difficulty of the patient in sustaining concentration exaggerated his deficits, but his overall neuropsychological profile was consistent with significant cerebral dysfunction. Routine hematology showed mild thrombocytopenia, increased free thyroxin values and marginally decreased calcium levels. Routine EEGs revealed on one occasion brief bursts of generalised epileptiform activity; however, successive EEGs as well as video-EEG monitoring failed to detect any abnormality. MRI of the brain using volumetric acquisition as well as echocardiogram proved normal. The patient was then extensively investigated in a tertiary university centre in order to exclude an underlying neurological disorder. Blood films for acanthocytes, serum copper and ceruloplasmin, slit lamp examination, antibasalganglia antibodies, white cell enzymes as well as very long chain fatty acids, plasma amino acids and urine organic acids were either normal or negative. The suspicious EEG findings led to skin biopsy for Lafora disease, which revealed no abnormality. Subsequently, a muscle biopsy was undertaken which provided no evidence for a mitochondrial encephalomyopathy. Finally, on readmission 2 years later a fluorescence in-situ hybridization (FISH) using the N25 probe was performed, which demonstrated a microdeletion within chromosome 22q11.2. It is well established that individuals with chromosome 22q11.2 deletion syndrome are at risk to develop a range of psychiatric illnesses. Early reports cite a high prevalence of psychotic disorders, specifically schizophrenia, among adults carrying the deletion and LETTER TO THE EDITORS