Mild Delay Research Articles

The Effects of Constant Time Delay and Instructive Feedback on the Acquisition of English and Spanish Sight Words

The authors of this study evaluated the acquisition of instructive feedback information presented to four kindergarten children with mild delays taught in dyads using a constant time delay (CTD) procedure. They also assessed the learning of observational (dyadic partner) information within this instructional arrangement. A multiple probe design across word sets, replicated across the four participants, was used to evaluate the efficacy of the CTD procedure and instructive feedback on the students’ expressive English sight word identification, the corresponding Spanish translations, and other students’ target words. Results showed that all participants acquired high percentages of their targeted English sight words, as well as targeted Spanish translations taught through an instructive feedback procedure. Lower percentages of non-targeted English and Spanish words were acquired through observational learning.

Microdeletions involving Chromosomes 12 and 22 Associated with Syndromic Duane Retraction Syndrome

Background: Duane retraction syndrome (DRS) is the most common of the congenital cranial dysinnervation disorders (CCDDs). CCDDs can be monogenic or chromosomal in origin. Identification of the genetic cause(s) in patients and families with DRS facilitates definitive diagnosis and provides insights into these developmental errors.Materials and Methods: This study described a young girl with DRS on the left and several additional developmental abnormalities. Clinical examination including neuroimaging, sequencing of candidate genes associated with DRS, and array comparative genomic hybridization (array CGH) were performed.Results: The proband had unilateral DRS type 3 on the left with somewhat low-set ears, mild motor delay with normal intelligence, and an asymmetric neck without a palpable right sternocleidomastoid muscle. Spine X-rays revealed a Klippel-Feil syndrome (KFS) and an MRI showed a webbed neck. She also had spina bifida at C8-T1 and a submucosal cleft palate. The parents of the proband were related with no other family member affected similarly. Sequencing of SALL4, CHN1, HOXA1, and TUBB3 did not show any mutation. Array CGH revealed de novo deletions of 21 Kb on chromosome 12q24.31 and 11 Kb on chromosome 22q13.31, each encompassing only one gene, ring finger protein 34, E3 ubiquitin protein ligase (RNF34) and peroxisome proliferator-activated receptor alpha (PPARA) respectively.Conclusions: This patient presents an unusual phenotype associated with a unique combination of two chromosomal microdeletions.

Genotype–phenotype relationship in a child with 2.3 Mb de novo interstitial 12p13.33-p13.32 deletion

Microdeletion 12p13.33, though very rare, is an emerging condition associated with variable phenotype including a specific speech delay sound disorder, labelled childhood apraxia of speech (CAS), intellectual disability (ID) and neurobehavioral problems.Here we report a de novo 2.3 Mb interstitial 12p13.33-p13.32 deletion in a 5 year-old child with mild ID, speech delay, microcephaly, muscular hypotonia, and joint laxity. In contrast to previously reported patients with 12p13.33 monosomy, our patient's interstitial deletion spans the 12p13.33-12p13.32 region with the distal breakpoint within intron 12 of CACNA1C.Phenotype–genotype comparison between our case, previously reported patients, and subjects with 12p13.33 deletions led us to propose that haploinsufficiency of CACNA1C may influence the variability of the patients' phenotype, since the gene resulted disrupted or entirely deleted in the majority of reported patients. In addition, phenotypic features such as microcephaly, muscular hypotonia, and joint laxity are mainly present in patients with monosomy of 12p13.33 extending to the 12p13.32 portion. A common region of ∼300 kb, harbouring EFCAB4B and PARP11, is deleted in patients with microcephaly while a second region of ∼700 kb, including TSPAN9 and PMTR8, could be associated with muscle hypotonia and joint laxity. These data reinforce the hypothesis that multiple haploinsufficient genes and age-dependent observation may concur to generate the variable phenotype associated with 12p13.33 deletion.

Inaugural Cerebral Sinovenous Thrombosis Revealing Homocystinuria in a 2-Year-Old Boy

Cerebral sinovenous thrombosis is unusual during childhood and requires early and accurate management because of its detrimental consequences. We report on the case of a 2-year-old boy with mild psychomotor delay, who presented with nonfebrile acute ataxia. A brain computed tomographic (CT) scan showed complete thrombosis of the superior sagittal sinus, confirmed by magnetic resonance angiography and associated with a right frontal hemorrhagic infarction. Systematic screening for thrombophilia revealed homocystinuria linked to cystathionine β-synthase deficiency with underlying compound heterozygosity. The evolution was favorable after anticoagulant therapy, specific diet, and vitamin supplementation. This case is of interest because of the unusual clinical presentation as a pediatric cerebral sinovenous thrombosis. Furthermore, homocystinuria is rarely revealed by cerebral sinovenous thrombosis at the onset of the disease and should systematically be ruled out in pediatric stroke.

Hemimegalencephaly without epilepsy: case report

Hemimegalencephaly is a rare sporadic brain malformation characterized by enlargement of one cerebral hemisphere. The classical clinical triad consists of intractable epilepsy, severe psychomotor delay and hemiparesis. In this report, we describe a case of a 3-year-old girl, with all the radiological features of severe hemimegalencephaly but with a comparatively benign clinical course. She had no hemiparesis, mild delay and no seizures. An extensive literature review reveals only one previously reported case of hemimegalencephaly with the absence of seizures, as part of case series. This is the first dedicated case report, with clinical description and radiological images, of this entity.

Case 2: A 20-month-old boy with asymmetric growth of the legs

A 20-month old boy with right-leg hyperplasia was referred to the authors’ institution for a genetic consultation. The child was born following an uncomplicated full-term pregnancy and delivery weighing 3150 g (20th percentile). There was no history of hypoglycemia in the newborn period. The parents first noticed a difference in the size of his legs when the child was one month of age. At four months of age, a leg circumference discrepancy was first documented (4 cm in the thigh and 2.5 cm in the lower leg). The child was referred to a vascular surgeon, who performed a Duplex ultrasound and documented normal arterial and venous blood flow, absence of arteriovenous malformations and varicosities, and possible lymphedema. At 12 months of age an orthopedic surgeon documented a leg length discrepancy of 2.5 cm. At the time of referral, the boy was in good general health; his weight was 14 kg (99th percentile), height 85 cm (62nd percentile) and head circumference 47 cm (31st percentile). Discrete hyperplasia on the right side of the face was noted. Examination revealed significant discrepancies in all leg measurements – the right leg was 2.5 cm longer, with increased circumference at the thigh (4 cm), knee (3 cm) and lower leg (2.5 cm) (Figure 1). On focused inspection, there was no evidence of leg swelling, port-wine stains, vascular nevi, omphalocele, macroglossia, subcutaneous lipomata or ear creases/pits. He exhibited mild expressive language delay but otherwise normal development. Further diagnostic evaluation suggested the underlying diagnosis. Figure 1) Photographs (left and centre panels) and x-ray (right panel) of the patient at six months of age

Reading Recovery teachers discuss Reading Recovery: a qualitative investigation

Reading Recovery is an early intervention program used around the world for at-risk readers. Developed at a time when constructivist principles dominated educational philosophy, its efficacy has caused debate and division over the last three decades. This qualitative study employed in-depth interviews and observations to explore 10 Reading Recovery teachers' views and experiences about working with the program. Findings revealed that the program was implemented by participants as originally prescribed and its contents were well regarded. However, deeper analysis revealed that Reading Recovery teachers held the view that the program was best suited for children with innocent deficits such as mild maturational delay but were not necessarily confident about its ability to meet the needs of children with various clinical conditions, including specific reading difficulty. Theoretical, ethical and clinical implications are explored regarding the utility of the Reading Recovery program as an early intervention program for low progress readers.

Assessing hematopoietic (stem-) cell behavior during regenerative pressure.

Hematopoiesis is a complex and strongly regulated process. In case of regenerative pressure, efficient recovery of blood cell counts is crucial for survival of an individual. We propose a quantitative mathematical model of white blood cell formation based on the following cell parameters: (1) proliferation rate, (2) self-renewal, and (3) cell death. Simulating this model we assess the change of these parameters under regenerative pressure. The proposed model allows to quantitatively describe the impact of these cell parameters on engraftment time after stem cell transplantation. Results indicate that enhanced self-renewal during the posttransplant period is crucial for efficient regeneration of blood cell counts while constant or reduced self-renewal leads to delayed recovery or graft failure. Increased cell death in the posttransplant period has a similar impact. In contrast, reduced proliferation or pre-homing cell death causes only mild delays in blood cell recovery which can be compensated sufficiently by increasing the dose of transplanted cells.

Reduction in Glutamine/Glutamate Levels in the Cerebral Cortex after Adrenocorticotropic Hormone Therapy in Patients with West Syndrome

West syndrome (WS), an intractable epileptic encephalopathy of infancy, is refractory to many antiepileptic drugs; however, adrenocorticotropic hormone (ACTH) is an effective treatment for WS. The mechanism behind the efficacy of ACTH is mediated by biochemical processes that remain unknown. We examined the effects of ACTH therapy with tetracosactide (TCS), a synthetic ACTH analogue, on brain metabolism in patients with WS, using (1)H magnetic resonance spectroscopy (¹H-MRS). In six patients with cryptogenic WS, we performed single-voxel ¹H-MRS at the occipital lobe cortex. Measurements were taken prior to TCS treatment, a few days after therapy, and several months after therapy. Data were also compared with subjects having only mild psychomotor delays. The metabolites measured were glutamine plus glutamate (Glx), N-acetylaspartate (NAA), choline (Cho), and myoinositol (mI); each was expressed as a ratio with creatine plus phosphocreatine (total creatine: tCr). The Glx/tCr ratio was significantly reduced after the TCS treatment. The NAA/tCr ratio was also significantly reduced after the treatment compared with the control group, although the change in NAA signal was heterogeneous among patients, correlating with respective outcomes. The Cho/tCr and mI/tCr ratios were not affected by TCS treatment. The reduction in Glx suggests a decrease in the glutamate-glutamine cycle, which plays a pivotal role in synthesizing neurotransmitters such as glutamate and GABA. TCS-induced Glx reduction may induce changes in synaptic signal transduction, thereby accounting for the effect of TCS on WS. The change in NAA indicates altered neuronal activity, which may be correlated with outcome in WS patients.

Molecular and phenotypic characterization of atypical Williams–Beuren syndrome

Williams-Beuren syndrome (WBS) is a multisystemic genomic disorder typically caused by a recurrent ˜1.5-1.8 Mb deletion on 7q11.23. Atypical deletions can provide important insight into the genotype-phenotype correlations. Here, we report the phenotypic and molecular characterization of a girl with a de novo 81.8 kb deletion in the WBS critical region, which involves the ELN and LIMK1 genes only. The patient presented at 2 months of age with extensive vascular abnormalities, mild facial dysmorphism and delays in her fine motor skills. We discuss potential molecular mechanisms and the role of ELN and LIMK1 in the different phenotypic features. We compare the findings in our patient with previously reported overlapping deletions. The phenotypic variability among these patients suggests that other factors are important in the phenotype and possibly include: position effects related to copy number variation size, variations in the non-deleted alleles, genetic modifiers elsewhere in the genome, or reduced penetrance for specific phenotypes.

Special Issues in Infants’ Speech and Language Development

Infants start learning language when they hear and respond to familiar voices. The process of speech and language development milestones helps to tell whether a child is developing a language as expected. Thus, certain skills such as babbling, saying “mama” or “dada” or putting two words together and gestures to say what it means and understand what others say are identifiable. A child usually needs to master one milestone before reaching the next. Some type of hearing loss can cause speech delay. Children with a speech delay should have their hearing tested. This could be caused by developmental disorders such a autism, which can cause speech delay. This paper examines special issues in infants’ speech and language development Speech and language problems are estimated to occur in about 6 out of 100 children. That means 94 out of 100 children could develop normally. Mild and temporary speech delays can occur. Some children learn new words faster than others do. If the child is not saying any word by 18 months or says fewer than 50 words by 24 months, specialist attention is required. The ages at which children reach milestones vary from child to child. Some children especially girls are advanced in speech and language than boys. A child who is surrounded by speech and language all the time usually learns language faster. The remedy for speech and language defect can be resolved or improved as prescribed by providing strategies for speech and language development. The paper accordingly points the way forward as a guide to all speech and language teachers, parents and caregivers. DOI: 10.5901/mjss.2013.v4n14p11

Clinical, Neuroimaging, and Genetic Characteristics of Megalencephalic Leukoencephalopathy With Subcortical Cysts in Egyptian Patients

BackgroundMegalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare and genetically heterogeneous cerebral white matter disease. Clinically, it is characterized by macrocephaly, developmental delay, and seizures. We explore the clinical spectrum, neuroimaging characteristics, and gene involvement in the first patients with megalencephalic leukoencephalopathy with subcortical cysts described from Egypt. PatientsSix patients were enrolled from three unrelated families. Patient inclusion criteria were macrocephaly, developmental delay, normal urinary organic acids, and brain imaging of diffuse cerebral white matter involvement. Direct sequencing of the MLC1 gene in patients' families and GliaCAM in one questionable case was performed using BigDye Terminator cycle sequencing. ResultsClinical heterogeneity, both intra- and interfamilial, was clearly evident. Developmental delays ranged from globally severe or moderate to mild delay in achieving walking or speech. Head circumference above the ninety-seventh percentile was a constant feature. Neuroimaging featured variability in white matter involvement and subcortical cysts. However, findings of posterior fossa changes and brain stem atrophy were frequently (66.6%) identified in these Egyptian patients. Discrepancy between severe brain involvement and normal mental functions was evident, particularly in patients from the third family. MLC1 mutations were confirmed in all patients. Deletion/insertion mutation in exon 11 (c.908-918delinsGCA, p.Val303 Gly fsX96) was recurrent in two families, whereas a missense mutation in exon 10 (c.880 C > T, p.Pro294Ser) was identified in the third family. ConclusionsThis report extends our knowledge of the clinical and neuroimaging features of megalencephalic leukoencephalopathy with subcortical cysts. It confirms the apparent lack of selective disadvantage of MLC1 mutations on gamete conception and transmission as supported by the presence of multiple affected siblings in Egyptian families.

A Case of Acute Pancreatitis Following Botulinum Toxin Injection of Lower Esophageal Sphincter

Purpose: We present a 77-year-old female with chronic back pain who was referred with complaints of daily nausea, acid reflux, weight loss, and solid and liquid dysphagia. A thorough evaluation was undertaken including gastric emptying study, abdominal CT, and impedance pH study, which were unremarkable apart from a mild delay in gastric emptying. We performed esophageal manometry which revealed a hypertensive and poorly relaxing LES which was treated with endoscopic Botox injection, leading to improvement in dysphagia. She returned to our clinic 4 years after her initial evaluation complaining of worsening nausea and dysphagia. CT enterography was unremarkable. Esophageal manometry was repeated and again pointed toward a hypertensive motor disorder. Esophageal body pressures were 357 mmHg at 3 cm above LES and 372 mmHg at 8 cm above LES (normal 35-180 mmHg at both locations). Barium swallow revealed esophageal dysmotility with decreased primary stripping wave and tertiary contractions. During the subsequent several months, she was tried on domperidone to improve gastric emptying but proved ineffective. Sublingual nitroglycerin was prescribed which improved her dysphagia but was discontinued due to hypotension. An upper endoscopy with Botox injection of the LES was repeated given her good initial response. The morning after the Botox injection she developed acute onset of severe abdominal pain. At her local hospital she received an abdominal CT revealing inflammatory changes adjacent to the tail of the pancreas and proximal portion of the stomach. Laboratories revealed a lipase of 9,243 as well as a normal bilirubin, alkaline phosphatase, and calcium. There was a mild elevation in AST and ALT of 189 and 72, respectively. Triglycerides were mildly elevated. She received an abdominal ultrasound which was unremarkable as well as an MRCP which showed no evidence of biliary stones or strictures. A month later we proceeded with an endoscopic ultrasound which showed a normal pancreas and common bile duct. To our knowledge, this is the first described case of presumed acute pancreatitis following Botox injection of the lower esophageal sphincter. Two weeks prior to the injection, the patient had a normal lipase of 49 and had never before suffered an episode of acute pancreatitis. She fully recovered and has not had a recurrence in the subsequent 10 months. Administration of botulinum toxin is generally felt to have a low rate of adverse reactions and complications which makes this case unexpected and clinically relevant given its frequent use to treat spastic gastrointestinal disorders such as achalasia.

P.10.13 Swallowing evaluation in adult neuromuscular patients

The aim was to investigate the swallowing physiology in adult neuromuscular patients who have swallowing disorders. Videofluoroscopic swallowing evaluation (VFSE) was done in adult neuromuscular patients who admitted to our clinic with swallowing disorders. Tongue elevation, retraction, swallowing reflex, hyolaryngeal elevation, the presence of residue, penetration, aspiration and esophageal motility disorders were evaluated. Tongue elevation, retraction and hyolaryngeal elevation was scored as absent, inadequate and exact. Swallowing reflex was noted as normal, mild, moderate and severe delay. Residue, penetration, aspiration and esophageal motility disorders were noted as absent and exact. The diet was determined as orally and non-orally according to swallowing evaluation. 31 patients with the mean age of 58.3 ± 12.7 years, mean height of 164.26 ± 9.6 cm and mean weight of 60.88 ± 15.5 kg were evaluated. 51.6% of patients were Amyotrophic Lateral Sclerosis, 22.6% of patients were motor neuron patients, 16.1% of patients were Myasthenia Gravis and 9.7% of patients were myopathic patients. 54.8% of patients had inadequate tongue elevation, 61.3% had inadequate tongue retraction and 51.6% had inadequate hyolaryngeal elevation. Despite 71% had normal swallowing reflex, 9.7% had mild, 9.7% had moderate and 9.7% had severe delay in swallowing reflex. 71% of patients had residue, 51.6% had penetration and 29% had aspiration. Esophageal motility disorders were determined in 35.5% of patients. 71% of patients (n: 22) were recommended oral intake and 29% (n: 9) were recommended non-oral feeding according to swallowing evaluation. Our results show that the swallowing disorders are based on inadequate peripheral structures in these patients. Although swallowing reflexes were normal, problems occurred. Deterioration in swallowing functions should be considered because of the progression of diseases.

Think About It

Fragile X syndrome (FXS) is one of the most frequent causes of mental retardation, intellectual disability, and autism. Most cases are the result of an expansion of the CGG trinucleotide repeat in the 5' untranslated region of the FMR1 gene and the subsequent functional loss of the related protein. We describe the case of a 4-year-old boy who clinically presents mild psychomotor delay without any major clinical dysmorphisms. Molecular analysis of the FMR1 gene showed mosaicism in terms of size and methylation, with one normal and 1 fully mutated allele, which is very rare in this syndrome. Physicians should therefore consider a diagnosis of FXS even if the patient's phenotype is mild. Although rare, diagnosing this condition has important consequences for the patient's rehabilitation and the family planning of parents and relatives.

Mitochondrial Encephalomyopathy Due to a Novel Mutation inACAD9

Mendelian forms of complex I deficiency are usually associated with fatal infantile encephalomyopathy. Application of "MitoExome" sequencing (deep sequencing of the entire mitochondrial genome and the coding exons of >1000 nuclear genes encoding the mitochondrial proteome) allowed us to reveal an unusual clinical variant of complex I deficiency due to a novel homozygous mutation in ACAD9. The patient had an infantile-onset but slowly progressive encephalomyopathy and responded favorably to riboflavin therapy. A 13-year-old boy had exercise intolerance, weakness, and mild psychomotor delay. Muscle histochemistry showed mitochondrial proliferation, and biochemical analysis revealed severe complex I deficiency (15% of normal). The level of complex I holoprotein was reduced as determined by use of Western blot both in muscle (54%) and in fibroblasts (57%). The clinical presentation of complex I deficiency due ACAD9 mutations spans from fatal infantile encephalocardiomyopathy to mild encephalomyopathy. Our data support the notion that ACAD9 functions as a complex I assembly protein. ACAD9 is a flavin adenine dinucleotide-containing flavoprotein, and treatment with riboflavin is advisable.

Usefulness of Parent-Completed ASQ for Neurodevelopmental Screening of Preterm Children at Five Years of Age

IntroductionPreterm children are at greater risk of developmental impairment and require close follow-up for early and optimal medical care. Our goal was to examine use of the parent-completed Ages and Stages Questionnaire (ASQ) as a screening tool for neurodevelopmental disabilities in preterm infants at five years of age.Patients and MethodsA total of 648 preterm children (<35 weeks gestational age) born between 2003 and 2004 and included in the regional Loire Infant Follow-up network were evaluated at five years of age. ASQ was compared with two validated tools (Intelligence Quotient and Global School Adaptation Score) and the impact of maternal education on the accuracy of this questionnaire was assessed.ResultsOverall ASQ scores for predicting full-scale IQ<85 and GSA score produced an area under the receiver operating characteristic curve of 0.73±0.03 and 0.77±0.03, respectively. An ASQ cut-off value of 285 had optimal discriminatory power for identifying children with IQ scores<85 and GSA scores in the first quintile. ASQ values<285 were significantly associated with a higher risk of non-optimal neurologic outcomes (sensitivity of 0.80, specificity of 0.54 for IQ<85). ASQ values>285 were not distinctive for mild delay or normal development. In children with developmental delay, no difference was found when ASQ scores according to maternal education levels were analyzed.ConclusionsASQ at five years is a simple and cost-effective tool that can detect severe developmental delay in preterm children regardless of maternal education level, while its capacity to identify children with mild delay appears to be more limited.

Developmental Hypothyroxinaemia Induced by Maternal Mild Iodine Deficiency Delays Hippocampal Axonal Growth in the Rat Offspring

Iodine is essential for the biosynthesis of thyroid hormones, including triiodothyronine and thyroxine. Thyroid hormones are important for central nervous system development. Mild maternal iodine deficiency (ID)-induced hypothyroxinaemia causes neurological deficits and mental retardation of the foetus. However, the detailed mechanism underlying these deficits is still largely unknown. Given that the growth-associated protein of 43 kDa (GAP-43), semaphorin 3A (Sema3A) and the glycogen synthase kinase 3β (GSK3β)/collapsin response mediator protein 2 (CRMP2) pathway are essential for axonal development, we hypothesise that hippocampal axonal growth-related proteins may be impaired, which may contribute to hippocampal axonal growth delay in rat offspring exposed to maternal hypothyroxinaemia. To test this hypothesis, maternal hypothyroxinaemia models were established in Wistar rats using a mild ID diet. Besides a negative control group, two maternal hypothyroidism models were created with either a severe ID diet or methimazole in the water. Our results showed that maternal hypothyroxinaemia exposure delayed offspring axonal growth on gestational day 19, postnatal day (PN) 7, PN14 and PN21. Consistent with this, the mean intensity of hippocampal CRMP2 and Tau1 immunofluorescence axonal protein was reduced in the mild ID group. Moreover, maternal hypothyroxinaemia disrupted expressions of GAP-43 and Sema3A. Furthermore, the phosphorylation of GSK3β and CRMP2 was also affected in the treated offspring, implying a potential mechanism by which hypothyroxinaemia-exposure affects neurodevelopment. Taken together, our data support the hypothesis that maternal hypothyroxinaemia may impair axonal growth of the offspring.

Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner–Hanhart Syndrome

Tyrosinemia type II, also designated as oculocutaneous tyrosinemia or Richner–Hanhart syndrome (RHS), is a very rare autosomal recessive disorder. In the present study, we report clinical features and molecular genetic investigation of the tyrosine aminotransferase (TAT) gene in two young patients, both born to consanguineous unions between first-degree cousins. These two unrelated families originated from Northern and Southern Tunisia. The clinical diagnosis was based on the observation of several complications related to Richner–Hanhart syndrome: recurrent eye redness, tearing and burning pain, photophobia, bilateral pseudodendritic keratitis, an erythematous and painful focal palmo-plantar hyperkeratosis and a mild delay of mental development. The diagnosis was confirmed by biochemical analysis. Sequencing of the TAT gene revealed the presence of a previously reported missense mutation (c.452G>A, p.Cys151Tyr) in a Tunisian family, and a novel G duplication (c.869dupG, p.Trp291Leufs*6). Early diagnosis of RHS and protein-restricted diet are crucial to reduce the risk and the severity of long-term complications of hypertyrosinemia such as intellectual disability.

576 kb deletion in 1p36.33–p36.32 containing SKI is associated with limb malformation, congenital heart disease and epilepsy

1p36 deletion (monosomy 1p36) is one of the most common terminal deletions observed in humans, characterized by special facial features, mental retardation, heart defects, development delay and epilepsy. Previously, we reported molecular findings in patients with limb, congenital heart disease (CHD) and other malformations with SNP-array. In a syndromic patient of the same cohort, we detected a small deletion of 1p36.33–p36.32 containing SKI (Sloan–Kettering Institute protooncoprotein). Recently, dominant mutations in SKI were identified to be correlated with Shprintzen–Goldberg syndrome. Retrospective examination revealed this patient with limb malformations, CHD, epilepsy and mild development delay. Together with previous reports, our study suggests that the 1p36.33–1p36.32 deletion encompassing SKI may represents a previous undescribed microdeletion disorder.