History Of Developmental Delay Research Articles

Choreoathetosis, congenital hypothyroidism and neonatal respiratory distress syndrome with intact NKX2‐1

Mutations in the NK2 homeobox 1 gene (NKX2-1) cause a rare syndrome known as choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome (OMIM 610978). Here we present the first reported patient with this condition caused by a 14q13.3 deletion which is adjacent to but does not interrupt NKX2-1, and review the literature on this condition. The infant presented at 23 months with a history of developmental delay, hyperkinesia, recurrent respiratory infections, neonatal respiratory distress, and hypothyroidism. Choreiform movements and delayed motor milestones were first noted at 6-8 months of age. TSH levels had been consistently elevated from 8 months of age. The clinical presentation was suggestive of an NKX2-1 mutation. Sequencing of all exons and splice site junctions of NKX2-1 was performed but was normal. Array CGH was then performed and a 3.29 Mb interstitial deletion at 14q13.1-q13.3 was detected. The distal region of loss of the deletion disrupted the surfactant associated 3 (SFTA3) gene but did disrupt NKX2-1. Findings were confirmed on high resolution SNP array and multiplex semiquanitative PCR. NKX2-1 encodes transcriptional factors involved in the developmental pathways for thyroid, lung, and brain. We hypothesize that the region centromeric to NKX2-1 is important for the normal functioning of this gene and when interrupted produces a phenotype that is typical of the choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome, as seen in our patient. We conclude that deletions at 14q13.3 adjacent to but not involving NKX2-1 can cause choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome.

The Relationship Between Self-Reported Neuropsychological Risk Factors and RBANS Test Performance Among Forensically Committed Psychiatric Inpatients

Patients who are committed to a psychiatric inpatient hospital are at increased risk for neuropsychological compromise. This study investigated a large (n = 260) and diverse sample of patients at a forensic state psychiatric hospital. A substantial proportion (35.8%) of the sample performed two standard deviations below the normative mean on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). In addition, 65% of the participants reported a history of developmental delays, less than 12 years of education, or past learning difficulties. Participants who reported these developmental and academic problems performed worse on the RBANS compared with those without such a history. Additionally, the more developmental/educational risk factors a participant reported, the more likely they were to be impaired on the RBANS. Half of the sample reported a history of at least one neurological risk factor (e.g., history of head injury with loss of consciousness). However, in this sample, a history of neurological risk factors did not influence overall performance on the RBANS and did not increase the likelihood of impairment. These results speak to the relevance of neuropsychological services at state psychiatric hospitals and provide some evidence that a history of developmental or academic problems may help identify psychiatric patients with neuropsychological compromise.

Hereditary multiple exostoses, macrocephaly, congenital heart disease, developmental delay, and mental retardation in a female patient: A possible new syndrome? Or new association?

Hereditary multiple exostoses (HME) or multiple osteochondromas are an autosomal dominant condition and are genetically heterogeneous. It is characterized by development of two or more cartilage capped bony outgrowths (osteochondromas) of the long bones. Osteochondromas develop and increase in size in the first decade of life, ceasing to grow when the growth plates close at puberty. HME type-I is caused by mutation in the gene encoding exostosin-1 EXT1, which maps to chromosome 8q24. Type-II is caused by mutation in the gene encoding exostosin-2 EXT2 on chromosome 11p12-p11; and type III has been mapped to a locus on chromosome 19, EXT3. We report a de novo case of HME at the Kuwait medical genetic centre (KMGC) came for consultation regarding her poor school performance. She has painless bony swellings over her extremities, macrocephaly, congenital heart disease, obesity, history of developmental delay, and moderate mental retardation. Fluorescent In Situ Hybridization (FISH) analysis done using probes specific for regions 8p22/CEP8/& 8q24.12-8q24.13 showed delineation of two copies of normal sized chromosome 8; also Cycline D1 for 11q13 locus and CEP11, telomeric regions 11q & 11p, all showed normal signals. Telomeric 19p was used to rule out any deletion of 19p and was normal too.

Azithromycin-Associated Choreoathetosis

Researchers at Women and Children's Hospital of Buffalo, NY, report an 11- year-old boy with a history of developmental delay who developed transient agitation and choreoathetoid movements of upper extremities in temporal relation to treatment of influenza A and B respiratory infections with oral azithromycin on 2 occasions.

Valproate-Induced Worsening of Seizures

The use of valproate sodium as an antiepileptic is not advised in children with an undiagnosed metabolic condition because of the increased risk of hepatotoxicity and encephalopathy. Here the authors describe a 2.5-year-old girl with a history of developmental delay, failure to thrive, and a seizure disorder whose seizures worsened after the introduction of valproate sodium. This led to a search for an underlying metabolic disorder, and after extensive investigations, a diagnosis of nonketotic hyperglycinemia was made. In this report, the authors discuss the metabolic conditions that can be worsened by valproate sodium. Valproate sodium interferes with the glycine cleavage enzyme synthesis in the mitochondria, hence increasing glycine levels. The increased glycine levels are responsible for worsening of the underlying metabolic condition and increased seizure frequency.

Tracheobronchial Remnants: A Rare Congenital Anomaly

An 11-year-old male patient with a history of developmental delay, deafness, reactive airway disease, chronic gastroesophageal reflux disease, subglottic stenosis, Nissen fundoplication, and gastrostomy placement in infancy had his gastrostomy removed at age 10 and presented to our outpatient office 2 months later complaining of persistent leakage from the gastrocutaneous fistula. There was no coughing, gagging, or choking with oral feeds. He underwent an esophagogastroduodenoscopy to close the fistula via clipping, and an incidental finding of an irregular patch of nodular mucosa was visualized in the mid-esophagus.

Screening for Developmental Delay in High-Risk Users of an Urban Pediatric Emergency Department

To determine whether screening children in an urban pediatric emergency department (PED) would lead to identification of previously undiagnosed developmental delay. This was a cross-sectional study of families presenting to an urban public hospital PED with children 6 to 36 months and no history of developmental delay. Children were screened for possible developmental delay using the Ages and Stages Questionnaire; parents completed an instrument that assesses 5 domains: communication, gross motor, fine motor, problem solving, and personal-social. Sociodemographic data were also obtained. One hundred thirty-eight children were enrolled, all accompanied by their mothers. Mean age of the children was 18.9 months; 51.5% were female; 56.8% of the mothers were high-school graduates; 59.9% were immigrants; 75.4% were Latino. Twenty-one percent did not have a regular source of primary care; 26.8% (95% confidence interval, 20.1%-34.8%) screened positive in at least 1 domain, with a trend toward the highest percentage of positive screens on the communication domain (z = 1.89, P = 0.059). In a simultaneous multiple logistic regression model including all predictor variables, child age of 12 to 30 months was associated with increased adjusted odds of positive screen (adjusted odds ratio, 8.4; 95% confidence interval, 1.4-48.9). Having a primary caregiver born in the United States was statistically significant for screening positive in at least 1 Ages and Stages Questionnaire domain (P = 0.03). Almost 30% of 6- to 36-month-old children presenting to an urban PED without prior developmental concerns screened positive for possible delay, suggesting the utility of performing routine developmental screening in the PED. Pediatric emergency department use alone may be an indication for screening. Further study is needed for feasibility of screening for delay in the PED.

13q13.1–q13.2 deletion in tetralogy of Fallot: Clinical report and a literature review

Recent advances in microarray technology are helping to identify more genetic anomalies associated with tetralogy of Fallot and other congenital heart defects. We report on a 24-year-old woman with a syndromic form of tetralogy of Fallot who was found to have a novel de novo deletion of the proximal long arm of chromosome 13. History of developmental delay and learning difficulties, mild dysmorphic facial features, and anal atresia prompted genetic investigations. A review of the literature on deletions that overlap this region showed that several were associated with major congenital heart defects. The results suggest that the 13q13.1-q13.2 region may harbour a gene or genes important in cardiac development.

Isolated Innominate Artery as a Cause of Subclavian Steal and Cerebral Hemisphere Atrophy

A rare case of isolated innominate artery arising from a left persistent arterial duct with a right aortic arch is presented. Of interest in this case is the retrograde flow in the left carotid system, the history of developmental delay, and the magnetic resonance image (MRI) brain findings suggestive of asymmetric volume loss affecting the left cerebral hemisphere. The authors postulate a possible mechanism of subclavian steal.

A Child with REM Sleep Disturbance

An 8-year-old patient presented with history of snoring. He also had complaints of an upset stomach at night and talking during sleep. The child reportedly banged his head or rocked his body when going to sleep. He woke more than twice per night on average, and her had trouble falling back asleep. Epworth Sleepiness Scale score was 3. His teacher commented that he appeared sleepy during the day. His only medication was methylphenidate (Ritalin) for attention deficit hyperactivity disorder (ADHD). There was no history of developmental delay or mental retardation. Physical examination: Average built male child in no acute distress. Tonsils not enlarged. Respiratory, cardiac and neurological examination was normal. Tracings from the polysomnography are shown in Figures 1, ​22,​33,and ​44. Video clip from the polysomnography is available online at www.aasmnet.org/jcsm. Figure 1 Epoch length of 10 seconds Figure 2 Epoch length of 30 seconds Figure 3 Epoch length of 120 seconds Figure 4 Epoch length of 120 seconds (Different time period) Q: What is going on wth this patient in sleep? What is the diagnosis? A: Rhythmic movement disorder (RMD). The patient is in REM sleep. Note the total lack of the expected muscle atonia (leg EMG) during REM sleep. This is due to rhythmic movement disorder (RMD). The motion artifacts on EEG are also secondary to RMD. Diagnosis: Rhythmic movement disorder during REM sleep The child presented with RMD in the form of body rolling during each REM phase. The typical rapid eye movements during REM continued to be observed while the body thrashed around in a rhythmic pattern (clearly visible in the video clip). This behavior continued till the child shifted out of the REM phase, when it would suddenly end followed by a regular sleep pattern. Background EEG during these movements (see Figures) is predominantly low voltage mixed frequency with no alpha or delta predominant rhythm, differentiating it from wakefulness state. REM behavior disorder (RBD) is ruled out as there is no complex dream enactment; instead, the movements are rhythmic and repetitive. Also, there was no dream recall as is typically seen in RBD. Moreover, the patient had a complete neurological evaluation with a sleep and wake electroencephalogram (EEG) prior to the sleep study, showing no evidence of epilepsy. RMD represents an unusual variety of childhood parasomnias characterized by repetitive motion of the head, trunk, or extremities. RMD is defined by the International Classification of Sleep Disorders as a group of stereotyped, repetitive movements by the large muscles, usually of the head and neck, which typically occur immediately prior to sleep onset and are sustained into light sleep.1 However, RMD has been rarely reported during REM sleep, a sleep stage when typically the muscle activity is completely absent.2 It is typically observed in infants and young children presenting as head banging, head rolling, body rolling, or body rocking. The prevalence of RMD is high in infants younger than 9 months of age (up to 66%). It persists in approximately 30% of children at the age 4 years and usually disappears by 10 years of age.3 Very rarely do the symptoms persist into adolescence and adulthood.4,5 RMD is rarely described in REM sleep. Kohyama et al. reviewed 33 patients with RMD. Eighteen of the 33 RMD patients experienced episodes during REM sleep. Among the 18 patients who had episodes during REM sleep, 8 experienced the episodes exclusively during REM sleep.2 Most children who have RMD are healthy, although the condition may also be seen in association with autism and other developmental disabilities, especially if it persists in older children or adults. In one study, a strong association between RMD and ADHD was found in school-aged children. The authors proposed that pathogenetic mechanisms similar to those in ADHD are involved in RMD or that symptoms of ADHD may be secondary to RMD.6 For most affected children, RMD is a self-limited condition that does not require treatment. For children who suffer from particularly violent movements, use of protective padding in the crib or bed is recommended. Drug treatment of RMD has not been systematically studied in children, and a few isolated case reports address pharmacotherapy for this population. Clonazepam, oxazepam, and citalopram have been used with variable success.7 This disorder requires prompt and accurate recognition, as it may occasionally resemble nocturnal seizures and can cause injury to the patient.

Tremor in 48,XXYY syndrome

The 48,XXYY syndrome is a form of sex chromosome aneuploidy presenting in 1:18,000 males. Tremor has been previously reported in 47,XXY and 47,XYY syndromes, but has not been well described in 48,XXYY syndrome. Ten males with 48,XXYY syndrome had a standardized neurological examination and videotaping, which included the Clinical Rating Scale for Tremor and the International Cooperative Ataxia Rating Scale. All 10 cases had postural and kinetic tremor on physical examination. Other findings included mild gait ataxia, dysarthria, and nystagmus. Three cases are reviewed. Tremor is a common finding in children and young adults with 48,XXYY syndrome. Dosage alteration of genes on the sex chromosomes may be involved in the pathogenesis of this tremor. Karyotyping should be considered in individuals presenting with tremor and a history of developmental delay, learning disabilities, tall stature, or microorchidism.

Subclinical seizures in children diagnosed with localization-related epilepsy: Clinical and EEG characteristics

Objective Subclinical seizures (SCSs) are characterized by paroxysmal rhythmic epileptiform discharges that evolve in time and space in the absence of objective clinical manifestation or report of a seizure. The aim of this study was to evaluate the frequency and characteristics of SCSs in children with localization-related epilepsy (LRE). Methods The results of video/EEG monitoring were reviewed to identify patients with SCS. We identified 187 children diagnosed with LRE, in 32 of whom SCSs were reported in the EEG recording. Results SCSs were reported only in the children who had received a diagnosis of either symptomatic or cryptogenic LRE. All children had a history of clinical seizure(s). The ictal onset of SCSs was most frequent from the temporal and frontal lobes. SCSs were lateralized to the left hemispheres in 19, right hemisphere in 8, and both hemispheres independently in 5 children. SCSs were more often reported in young children, and associated with a history of developmental delay, infantile spasms, and frequent seizures. EEG abnormalities included background slowing and lack of normal sleep architecture in addition to the epileptiform activity. Seizure freedom was reported less often in children with SCSs. Six patients seizure free at the time of the admission were found to have SCSs. Conclusion Subclinical seizures are not uncommon in children with LRE, in particular, with younger age, developmental disability, and medically refractory clinical course. Video/EEG monitoring will be informative in selected children with LRE to assess the seizure frequency more accurately.

Visual Diagnosis: A Child Who Has Hyperpigmented Spots and a Forearm Deformity

1. Mohammed Al-Owain, MD* 2. Maha Faden, MD† 3. Aziza Chedrawi, MD* 1. *King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia 2. †Department of Pediatrics, Riyadh Medical Complex, Riyadh, Saudi Arabia A 10-year-old boy who has multiple hyperpigmented spots on his skin and a deformed left forearm since birth presents to a tertiary care center for additional evaluation. He was born at term via vaginal delivery. He has been healthy except for functional and cosmetic problems related to his deformed left forearm. The family resides in a locale that lacks advanced health-care services. In the past, a local health practitioner informed the family that their child's skin lesions and limb deformity were congenital and no treatment was available. No surgical correction has been attempted. However, recent evaluation by a pediatrician prompted referral to the tertiary care center. The child has no history of developmental delay, and his school performance is average for age. His vision and hearing are normal. His parents are first cousins, and he has four healthy siblings. Family history is otherwise unremarkable, with no history of multiple hyperpigmented skin lesions or limb deformities. Physical examination reveals an alert, short, and underweight child whose facies are normal. His weight is 21 kg (∼5th percentile), height is 124 cm (∼5th percentile), and head circumference is 52 cm (50th percentile). All vital signs are normal. Skin examination reveals multiple hyperpigmented skin macules of variable sizes and shapes scattered over the trunk, back, and upper and lower limbs (Fig. 1). Two palpable, firm skin nodules measuring 1×2 cm are present on the lateral aspect of his neck and back. Eye examination suggests raised spots on the irises. Examination of the hair, nails, ears, nose, throat, chest, heart, abdomen, and genitalia yields normal results. Musculoskeletal examination reveals marked bowing of the left forearm, although the hand and digits appear normal (Fig. 2). Results of the neurologic examination are unremarkable. Figure 1. Multiple variably sized and shaped hyperpigmented macules on the back. Figure 2. Bowing of the left …

Evaluation of a child for secondary causes of obesity and comorbidities

A 15-year-old boy who had been overweight since the age of 6 months was referred to an adolescent obesity clinic for further assessment of his comorbidities and management of his obesity. The patient had no history of developmental delay or abnormal growth velocity. He had previously tested negative for Prader-Willi syndrome and the melanocortin-4 receptor gene mutation. The patient had made numerous attempts at weight loss in the past, but any weight loss he achieved had been temporary. At presentation, the patient had a BMI of 52.3 kg/m(2), a waist circumference of 156 cm, blood pressure of 130/85 mmHg and severe acanthosis nigricans in the cervical and axillary skin folds. Measurement of height, weight, waist circumference and blood pressure; screening tests, including a fasting glucose test, 2 h glucose-tolerance test, measurements of blood lipids and liver function tests. Morbid obesity, metabolic syndrome, nonalcoholic fatty liver disease, impaired glucose tolerance and dyslipidemia. The patient was assigned to an extensive lifestyle-modification and behavior-modification program, with clinic-based follow-up every 4 weeks.

Silver hair in a 3-year-old

Conflict of interest: none declared. A 32‐month‐old girl of Pakistani origin, whose parents were first cousins, was referred to the paediatric department with a short history of abdominal pain, lethargy and a history of developmental delay. She became progressively unwell, developed neck stiffness and refused to walk. A diagnosis of acute meningitis was made, and a pre‐lumbar puncture computed tomography scan showed hydrocephalus with enlarged third and lateral ventricles, which was treated by ventriculostomy. Magnetic resonance imaging showed multiple enhancing lesions in the cerebellum. She was referred for a dermatological opinion as she was noted to have silver hair and eyebrows (Fig. 1). ... Histological examination of a cerebellar lesion showed evidence of a histiocytic tumour with a degree of erythrophagocytosis and lymphophagocytosis (Fig. 2). ... What is your diagnosis? Griscelli's syndrome. Griscelli's syndrome (GS) is a rare autosomal recessive condition resulting in partial albinism with immunodeficiency.1 There is usually absent or impaired delayed‐type hypersensitivity, hypogammaglobulinaemia and impaired natural killer‐cell function. Patients with this syndrome are predisposed to ‘accelerated phases’ with lymphohistiocytic infiltration of several organs including liver, bone marrow and brain, although the latter is rarely reported. These episodes are often associated with infections, particularly Epstein–Barr virus (EBV), as in our case, where PCR performed on the blood was positive for EBV.

A Child With Muscle-eye-brain Disease

Purpose: To describe a child with muscle-eye-brain disease as the first case report in Korea. Case Summary: A 35-month-old girl presented with esotropia and nystagmus since birth. She was born with a birth weight of 3.45 Kg at the gestational age of 39 weeks. She had a history of developmental delay and developmental dislocation of the hip. Her elder sister also had generalized weakness and mental retardation. The patient's creatinine kinase and lactate dehydrogenase serum levels were high. Cycloplegic refraction showed a significant myopic astigmatism in both eyes. She showed nystagmus and 20 prism diopters of esotropia in the primary position with the alternative prism cover test. Slit lamp examination revealed a mild posterior subcapsular cataract and lower lid epiblepharon in both eyes. Funduscopic examination showed diffuse retinal degeneration with remnant hyaloids membranes in both eyes. Both optic nerves were dysplastic with abnormal vascular branching pattern. Flash visual evoked potential was normal and standard electroretinography showed decreased amplitude in both eyes. Brain magnetic resonance imaging (MRI) revealed diffuse T2 high signal lesions of the cerebral white matter, diffuse pachygyria of the cerebral cortices, pontine hypoplasia, and multiple small cerebellar cysts. Conclusions: When a child with developmental delay has ophthalmologic problems including severe myopia, cataract, strabismus and retinal degeneration, the systemic condition should be examined. In this case, in addition to the ophthalmologic findings, blood test and brain MRI were helpful for the diagnosis of muscle-eye-brain disease.

Lenguaje e inteligencia de preescolares: Análisis de su relación y factores asociados

ABSTRACT Preschoolers language and intelligence: Associated factors and relationship analysis Background: Language and intelligence are brain superior functions and their development is vital forschool and future work performance. Objective: To establish the correlation between language andintelligence, in order to identify possible factors involved in preschoolers of low socioeconomical status. Methods: Prospective and blind study that performs specific language tests, audiometry, WPSSI andpediatric-neurological examination to all children between 3-5 year-old attending a daycare, belonging tofamilies of low socioeconomical conditions at the Metropolitan Region of Chile, during 2007. Children withmajor diseases, explaining language difficulties (LD) were excluded. Results: 61 preschoolers, in which 22(36%) LD were identified. Cognitive performance presented a normal distribution (mean 92,69 +15). Therewas a significant correlation between intelligence and language (p 0.002). Children with LD had lowercognitive performance, both in verbal (p 0.004) and in manual tests (p 0.0007). The family history of LD orlearning difficulties and history of developmental delay were associated with a lower language performan-ce (p 0,05 and p < 0.0000, respectively). Children of mothers with superior studies showed better scores intheir cognitive potential (p 0.0079).

Outcomes Studies of Epiglottic and Base of Tongue Prolapse in Children

The purpose of this study was to compare previously reported flexible fiberoptic laryngoscopy (FFL) findings of a grading system for children with epiglottic and base of tongue (EBT) prolapse with findings at follow-up FFL. Surgical outcomes and tracheotomy decannulation are also reported. : Retrospective medical record review. Fourteen children with EBT prolapse had transnasal FFL in the supine position on at least two occasions. Findings were graded for initial versus most recent FFL. The previously published EBT prolapse grading system was reapplied. Mean age was 8.7 years at the last evaluation. Mean interval between initial and most recent FFL was 1.9 years. At follow-up FFL, six (43%) children had the same grade of EBT prolapse, five (36%) had a milder grade, and three (21%) had a more severe grade. Five (36%) children were decannulated, and nine (64%) children remain tracheotomy dependant. Of nine children who had surgery, four (44%) were decannulated. Eight (89%) of nine children who were not decannulated have a history of developmental delay (P < .03). Twelve (86%) children had gastroesophageal reflux disease, and six (43%) had abnormal swallowing function. The grading system was successfully reapplied to compare initial with follow-up findings in a cohort of children with EBT prolapse. Gastroesophageal reflux disease and swallowing dysfunction are common in this population. Judicious surgery may have some efficacy for EBT prolapse in selected patients. Many children with EBT prolapse still require tracheotomy, especially those with developmental delay.

A case of valproate-induced hyperammonemic encephalopathy: look beyond the liver

An 18-year-old woman presented to hospital with a 2-day history of decreased consciousness, nausea and vomiting. She had started taking valproate (750 mg/d) 2 weeks before for the treatment of temporal lobe epilepsy. The patient had no history of developmental delay or metabolic defects. She was

Anaplastic ganglioglioma arising from a Lhermitte–Duclos-like lesion

The authors report the case of a 7-year-old boy with a history of developmental delay who presented with aggressive behavior. A magnetic resonance (MR) image showed a mass lesion originating from the cerebellar vermis with an atypical folial pattern and contrast enhancement. Histologically, the subtotally resected specimen consisted mostly of neuropil with nodular foci of ganglion cells. Lhermitte-Duclos disease (LDD) was diagnosed in the patient. A retrospective review of the tissue sections showed a nidus of associated astrocytic proliferation, suggesting a diagnosis of ganglioglioma. Five years later, the patient experienced an altered mental state and a facial droop. An MR image revealed a cerebellar mass with cystic areas and an enhancing nodule. The resected tissue specimen consisted primarily of a mixed proliferation of glial and ganglion cells consistent with a ganglioglioma. Two years later, a third craniectomy was performed in the patient for worsening headache and ataxia. Histologically, the tumor showed progressive anaplasia and was most accurately classified as an anaplastic ganglioglioma. Immunohistochemically, most of the tumor cells were immunoreactive for anti-phospho-mammalian target of rapamycin (mTOR) and phospho-S6 ribosomal protein antibodies. In contrast, the subpopulation of neoplastic ganglion cells in the tissue, particularly from the first surgery, did not express phosphatase and tensin homolog deleted from chromosome 10 (PTEN). This immunohistochemical pattern suggests that the large dysplastic ganglion cells (the gangliocytomatous component) forming the greater part of the lesion were associated with activation of the phosphatidylinositol 3-kinase-PTEN/Akt/mTOR signaling pathway, a feature previously reported in LDD. This case represents the first report of an anaplastic ganglioglioma arising in an LDD-like lesion.