Interstitial Deletion Of Chromosome Research Articles

A rare KMT2A::CBL transcript in an acute monoblastic leukemia patient with an unfavorable outcome

BackgroundLysine [K] methyltransferase 2A (KMT2A, previously known as MLL) gene rearrangements are common in acute leukemias of various lineages and are associated with features such as chemotherapy resistance and rapid relapse. KMT2A::CBL is a rare fusion of unknown pathogenesis generated by a unique interstitial deletion of chromosome 11 that has been reported across a wide age range in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. The leukemogenic effect of the KMT2A::CBL rearrangement and its association with clinical prognosis have not been well clarified.Methods and resultsWe report the case of a 64-year-old female who was diagnosed with acute monoblastic leukemia (M5a) and who acquired the rare KMT2A::CBL fusion. The patient received multiple cycles of therapy but did not achieve remission and eventually succumbed to severe infection and disease progression. Additionally, we characterized the predicted KMT2A-CBL protein structure in this case to reveal the underlying leukemogenic mechanisms and summarized reported cases of hematological malignancies with KMT2A::CBL fusion to investigate the correlation of gene rearrangements with clinical outcomes.ConclusionsThis report provides novel insights into the leukemogenic potential of the KMT2A::CBL rearrangement and the correlation between gene rearrangements and clinical outcomes.

A coalescence of two syndromes in a boy with interstitial deletion of chromosome 5P and 18Q

A coalescence of two syndromes in a boy with interstitial deletion of chromosome 5P and 18Q

Overlapping Interstitial Deletions of the Region 9q22.33 to 9q33.3 of Three Patients Allow Pinpointing Candidate Genes for Epilepsy and Cleft Lip and Palate

Introduction: Patients carrying interstitial deletions of the long arm of chromosome 9 show similar features. These phenotypes are often characterized by developmental delay, intellectual disability, short stature, and dysmorphism. Previously reported deletions differ in size and location spanning from 9q21 to 9q34 and were mostly detected by conventional cytogenetic techniques. Methods: Based on clinical features suggesting primarily chromosomal diseases, aCGH analysis was indicated. We report on de novo overlapping interstitial 9q deletions in 3 unrelated individuals presenting neurodevelopmental disorder and multiple congenital anomalies. Results: An 8.03-Mb (90 genes), a 15.71-Mb (193 genes), and a 15.81-Mb (203 genes) deletion were identified in 9q affecting 9q22.33q33.3. The overlapping region was 1.50 Mb, including 2 dosage-sensitive genes, namely EPB41L4B (OMIM #610340) and SVEP1 (OMIM #611691). These genes are thought to be involved in cellular adhesion, migration, and motility. The non-overlapping regions contain 24 dosage-sensitive genes. Conclusion: Besides the frequently described symptoms (developmental delay, intellectual disability, skeletal abnormalities, short stature, and dysmorphic facial features) shared by the patients with interstitial deletions of chromosome 9q reported thus far, two of our patients showed distinct forms of epilepsy, which were successfully treated, and one had a bilateral cleft lip and palate. Possible candidate genes for epilepsy and cleft lip and palate are discussed.

Novel 12 Mb interstitial deletion of chromosome 8p11.22-p21.2: a case report

BackgroundThe deletion of a short arm fragment on chromosome 8 is a rare cause of Kallmann syndrome and spherocytosis due to deletion of the FGFR1 and ANK1 genes.Case presentationThis case study describes a 4-month-old child with growth and psychomotor retardation, auricle deformity, microcephaly, polydactyly, a heart abnormality, and feeding difficulties. An approximately 12.00 MB deletion was detected in the 8p11.22-p21.2 region of chromosome 8. After sequencing, we found that 65 protein genes had been deleted, including FGFR1, which resulted in Kallmann syndrome. There was no deletion of the ANK1 gene associated with spherocytosis, consistent with the phenotype.ConclusionThis patient is a new case of short arm deletion of chromosome 8, resulting in novel and previously unreported clinical features.

Genomic profile of radiation-induced early-onset mouse B-cell lymphoma recapitulates features of Philadelphia chromosome-like acute lymphoblastic leukemia in humans.

Epidemiological studies have revealed a radiation-related increase in the risk of developing acute lymphoblastic leukemia (ALL). Our recent study revealed early induction and increased risk of precursor B-cell (pB) lymphomas in mice after radiation exposure. However, the genomic landscape of radiation-induced B-cell lymphomas remains unclear. To identify the relevant genetic alterations in mice, whole-exome sequencing was performed on both early-onset and late-onset B-cell lymphomas that developed spontaneously or after gamma-irradiation. In addition to multiple driver mutations, the data revealed that interstitial deletion of chromosome 4, including Pax5, and missense mutations in Jak3 are unique genomic alterations in radiation-induced, early-onset B-cell lymphomas. RNA sequencing revealed a pB-cell-type gene-expression profile with no involvement of known fusion genes for human ALLs in the early-onset B-cell lymphomas. Activation of Jak3/Stat5 signaling in early-onset B-cell lymphomas was validated using western capillary electrophoresis. Those features were similar to those of Philadelphia chromosome-like ALL. Our data suggest a critical role for Pax5 loss-of-function mutations in initiating B-cell leukemogenesis coupled with activation of Jak3/Stat5 signaling as a basis for the rapid development of radiation-induced pB-ALL. These molecular signatures for radiation-induced cancers will inform both risk assessment and potential targeted therapies for pB-ALL.

Case report: early aortic valve degeneration associated with interstitial deletion of chromosome 2\u201346,XX,del (2)(q31.3; q32.2)

BackgroundInterstitial deletions within the long arm of chromosome 2, involving the 2q31q33 region, are rare but are known to be associated with delays in development, behavioral problems, facial dysmorphism and various hand/foot anomalies.Case presentationHere, we describe a case with an interstitial 2q31.3.q32.2 deletion, presenting the previously described phenotype, exhibiting fibromyxoid degeneration of the aortic valve in addition to previously described clinical features.ConclusionInterstitial deletion in chromosome 2q31.2q32.3 might be associated to a fibromyxoid degeneration of valvular leaflets generating regurgitation. Patients diagnosed with this mutation may require investigation to rule out a valvular disease.

Interstitial chromosomal deletion of the tuberous sclerosis complex 2 locus is a signature for radiation-associated renal tumors in Eker rats.

Ionizing radiation can damage DNA and, therefore, is a risk factor for cancer. Eker rats, which carry a heterozygous germline mutation in the tumor‐suppressor gene tuberous sclerosis complex 2 (Tsc2), are susceptible to radiation‐induced renal carcinogenesis. However, the molecular mechanisms involved in Tsc2 inactivation are unclear. We subjected Fischer 344 × Eker (Long Evans Tsc2 +/−) F1 hybrid rats to gamma‐irradiation (2 Gy) at gestational day 19 (GD19) or postnatal day 5 (PND5) and investigated the patterns of genomic alterations in the Tsc2 allele of renal tumors that developed at 1 year after irradiation (N = 24 tumors for GD19, N = 10 for PND5), in comparison with spontaneously developed tumors (N = 8 tumors). Gamma‐irradiation significantly increased the multiplicity of renal tumors. The frequency of LOH at the chromosome 10q12 region, including the Tsc2 locus, was 38%, 29% and 60% in renal carcinomas developed from the nonirradiated, GD19 and PND5 groups, respectively. Array comparative genomic hybridization analysis revealed that the LOH patterns on chromosome 10 in renal carcinomas were classified into chromosomal missegregation, mitotic recombination and chromosomal deletion types. LOH of the interstitial chromosomal deletion type was observed only in radiation‐associated carcinomas. Sequence analysis for the wild‐type Tsc2 allele in the LOH‐negative carcinomas identified deletions (nonirradiated: 26%; GD19: 21%) and base‐substitution mutations (GD19: 4%). Reduced expression of Tsc2 was also observed in the majority of the LOH‐negative carcinomas. Our results suggest that interstitial chromosomal deletion is a characteristic mutagenic event caused by ionizing radiation, and it may contribute to the assessment of radiation‐induced cancer risk.

Expression of Human SBDSR126T in Sbds Null Background Shows Eif6 Dysregulation: An Adult Zebrafish Model for Shwachman-Diamond Syndrome

Background. Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by pancreatic insufficiency, skeletal defects, neutropenia, and an increased risk of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). SDS occurs in 1/75,000 births, and biallelic mutations in the SBDS gene account for ~90% of patients. The SBDS protein is highly conserved. SBDS interacts physically with EFL1 to release EIF6 from the cytoplasmic pre-60S ribosomal subunit and promote the assembly of the mature 80S ribosome. The SBDS R126T allele is found in combination with the common K62X mutation in some SDS patient. A recent study showed that the SBDSR126T is not able to activate the GTPase activity of the EFL1, affecting the release of EIF6 from the 60S surface. Methods. We created a zebrafish knockout line that phenocopies the SDS with neutropenia, pancreas atrophy, small size (Figure 1A), and decreased 80S ribosomes. To rescue those fish from early mortality, we generated a new transgenic line Tg(ubi:SBDSR126T:pA) expressing the missense variant R126T, a disease-associated allele. Results. The sbds knockout fish die after 21 days post fertilization (dpf), corresponding to an early juvenile stage. However, the SBDSR126T transgenic line in the background of the sbds knockout can live for at least 12 months. This is in strong contrast to the mouse SbdsR126T/R126T line that do not survive to birth. Transgenically-rescued fish displayed a small size phenotype resembling SDS (Figure 1B). Levels of ribosomal proteins Rpl5 and Rpl11 were lower in the sbds knockout at 21 dpf but they were normal in the transgenic line at 6 months. We also observed a concordant regulation of Sbds and Eif6 expression (Figure 1C,D). sbds null fish showed a significant upregulation of cdkn1a, while in their transgenic siblings levels were normal (Figure 1E). Moreover, mpx was upregulated in the transgenic line with the null background (Figure 1F). Analysis of neutrophil and monocyte counts are being performed and will be reported. Conclusions. Our novel SBDSR126T zebrafish model survives until adulthood, which will allow us to carry out a number of informative assays such as stress response, gene expression, and polysome profiles in different organs. Rpl5 and Rpl11 levels are affected in sbds mutants but not in the transgenic line. Activation of cdkn1a (p21) in sbds mutants might lead to apoptosis and death. The normal levels of cdkn1a in the transgenic line might be non-deleterious, as loss of Tp53 activation can rescue some models of bone marrow failure. In addition, loss of sbds or expression of SBDSR126T affect Eif6 levels in zebrafish. Importantly, some patients with SBDS deficiency acquire interstitial deletions of chromosome 20, resulting in the loss of the EIF6 gene. This might be a potential mechanism to suppress the defect in ribosome biogenesis by reducing the copy number of the EIF6 gene and has been related to a lower risk of MDS/AML comparing to other SDS patients. Our adult model of Shwachman-Diamond Syndrome can provide new insights into the pathogenesis of SDS and its progression to malignancy, which can be used to identify novel targets for AML/MDS therapy. Figure 1 Disclosures No relevant conflicts of interest to declare.

A complex and cryptic intrachromosomal rearrangement generating the FIP1L1_PDGFRA in adult acute myeloid leukemia

Myeloid neoplasms with eosinophilia and abnormalities of the PDGFRA gene can benefit from therapy with tyrosine kinase inhibitors, therefore revealing the PDGFRA rearrangement is essential to ensure the best choice of treatment. The most common PDGFRA partner is the FIP1L1 gene, generating the oncoprotein FIP1L1/PDGFRA (F/P). In the majority of cases the F/P fusion gene originates from intrachromosomal rearrangement at band 4q12, and occasionally from chromosomal translocations. In both cases, the interstitial chromosomal deletion of a region involving the CHIC2 gene has been reported, which is cryptic by conventional karyotyping but detectable by Fluorescence In Situ Hybridization (FISH) analyses. Herein, we report an acute myeloid leukemia (AML) case presenting with eosinophilia; the F/P fusion gene originated from a new, cryptic and complex intrachromosomal rearrangement of 4q12. Classical FISH assay revealed abnormal hybridization signals, but the presence of the F/P chimaeric gene was demonstrated by molecular analysis. We performed molecular characterization of the chromosomal rearrangement and targeted Next-Generation Sequencing (NGS) analysis with a myeloid gene panel, revealing the presence of pathogenic genomic variants affecting the TET2 and ETV6 genes. These mutations were present as subclones at the disease onset and their clone size increased at relapse.

SUN-290 Responsiveness of Growth Hormone Therapy in a Patient with Complex Chromosome 4 q Interstitial Deletion

Background Information: Chromosome 4 q interstitial deletion is a rare chromosomal disorder characterized by post natal growth retardation, developmental delay, craniofacial dysmorphism and behavioral problems. Not only are the characteristics of growth failure in these patients ill defined, but their responsiveness to growth hormone (GH) treatment is also lacking in the literature. An index case of a 7 year old male with unique interstitial deletion of chromosome 4 q deletion at q13.3 and q22.12 with a normal segment in between presented with significant growth failure in early infancy and was treated with growth hormone as described below. Case Report: He was born at 36 weeks gestation with a birth weight of 4 pounds 6 ounces (3rd percentile) and a birth length of 19 inches (50th percentile). Pregnancy was complicated by oligohydraminos. Post natal course was complicated by feeding difficulties and jaundice. He grew along the 5th percentile till age 6 months and then started faltering off below the 3rd percentile in both height and weight. He was started on dense caloric formula but his growth parameters continued to decline. His intake was reported good and had no diarrhea or vomiting. A TFT obtained demonstrated a slightly elevated TSH of 9.4 mcIU/ml (reference range 0.4-9.2) and marginally low Free T4 of 0.76 ng/dl (reference range 0.89-1.48). He was started on a small dose of 12.50 mcg thyroxin daily which did not improve his growth (thyroxin was discontinued at age 4 ½ year). His chemistry panel, IGF-1 and IGFBP-3 obtained were all normal. A bone age was concordant with his chronological age. Karyotype was 46 XY. Comparative genomic hybridization (CGH) array revealed a de novo 2.2 Mb deletion at 4q 13.3 and 2.2 Mb deletion at 4q22.1-q22.3. Deletions were separated by 18.3 Mb of normal copy number sequence. Other tests obtained demonstrated a normal pituitary gland on brain MRI and no tethered cord on the spinal MRI. He was started on GH for small for gestational age indication at age 13 month. His height and weight percentile improved significantly from <1% at age 13 month to 5th% by age 2 year and has continued to grow along 10-12 % since age 4 year. His other associated medical problems include improving developmental delay (attends special class with IEP and speech therapy), sleep disturbances (on melatonin and clonidine), mild hypotonia (received OT and PT, now resolved), poor dental enamel (has needed 8 crowns), obstructive sleep apnea with high arched palate (status post turbinate reduction and CPAP), clinodactyly, hyperopia with astigmatism (wears glasses) and sacral dimple. His behavior problems include high anxiety and obsessive/perseveration behavior. Conclusions: Growth failure is a characteristic feature in patients with chromosome 4 q deletion. These patients with growth retardation when treated with GH may respond with improved growth velocity and weight gain and hence should be considered.

A Rare Co-occurrence of Intestinal Malrotation and Hirschsprung's Disease in a Neonate with 13q21.31q33.1 Interstitial Deletion Including the EDNRB Gene

We report a rare co-occurrence of intestinal malrotation and Hirschsprung's disease (HSCR) in a male neonate with a large 38.8 Mb interstitial deletion of chromosome 13 extending from q21.31 to q33.1 including the EDNRB gene, who presented with craniofacial dysmorphic features and central nervous system malformations. The loss of EDNRB gene in addition to bilateral hearing loss and HSCR suggested an additional diagnosis of Waardenburg-Shah's syndrome. This case highlights the fact that prior knowledge of this rare association in infants with 13q deletion syndrome would enable early diagnosis and prompt interventions to prevent gastrointestinal complications.

Biology of Acute Myeloid Leukemia (AML) with Monosomy of Chromosome 7 or Loss of 7q. a Study on 487 Patients Analyzed By Gene Expression Profile (GEP), Single Nucleotide Polymorphism (SNP) Arrays and Metabolomics

Biology of Acute Myeloid Leukemia (AML) with Monosomy of Chromosome 7 or Loss of 7q. a Study on 487 Patients Analyzed By Gene Expression Profile (GEP), Single Nucleotide Polymorphism (SNP) Arrays and Metabolomics

Cutaneous Non-Neural Granular Cell Tumors Harbor Recurrent ALK Gene Fusions.

Non-neural granular cell tumor (NNGCT; also known as primitive polypoid granular cell tumor) is a rare neoplasm composed of large ovoid cells with abundant granular cytoplasm, variable nuclear pleomorphism, and the potential for regional lymph node spread. In contrast to conventional granular cell tumor (GCT), NNGCT lacks S100 expression and can exhibit greater nuclear atypia and mitotic activity. Therefore, we investigated clinicopathologic features of 12 NNGCT, and also used next-generation sequencing to identify potential driver events in a subset of NNGCT and 6 GCT. NNGCT demonstrated mild-to-moderate nuclear pleomorphism, variable mitotic activity (0 to 10/10 high-power fields), and were S100. Genetic analysis of 5 cutaneous NNGCT revealed gene fusions involving the anaplastic lymphoma kinase gene (ALK) in 3 cases (60%). Specifically, an interstitial deletion of chromosome 2 resulting in an in-frame fusion of dyanactin 1 (DCTN1) to ALK was identified in 2 cases, and a translocation resulting in a fusion between sequestosome 1 (SQSTM1) on chromosome 5 and ALK was identified in one case. Two of 6 GCT (33%) showed gains of chromosome 7. No other molecular or chromosomal alterations were detected in NNGCT and GCT. ALK immunohistochemistry revealed weak-to-moderate positivity in 4/9 cutaneous NNCGT (44%) including all 3 tumors with ALK fusions. Three oral NNGCT lacked ALK expression. NNGCT with ALK immunostaining did not have morphologic features distinguishing them from those without ALK staining. Our results demonstrate that a subset of NNGCT harbor ALK fusions, suggest that NNGCT are molecularly diverse, and further substantiate NNGCT as distinct from GCT.

Tracking preleukemic cells in vivo to reveal the sequence of molecular events in radiation leukemogenesis

Epidemiological studies have demonstrated an increased leukemia incidence following ionizing radiation exposure, but to date, the target cells and underlying mechanisms of radiation leukemogenesis remain largely unidentified. We engineered a mouse model carrying a different fluorescent marker on each chromosome 2, located inside the minimum deleted region occurring after radiation exposure and recognized as the first leukemogenic event. Using this tailored model, we report that following radiation exposure, more than half of asymptomatic CBA Sfpi1GFP/mCh mice presented with expanding clones of preleukemic hematopoietic cells harboring a hemizygous interstitial deletion of chromosome 2. Moreover, following isolation of preleukemic hematopoietic stem and progenitor cells irradiated in their native microenvironment, we identified the presence of Sfpi1 point mutations within a subpopulation of these preleukemic cells expanding rapidly (increasing from 6% to 55% in 21 days in peripheral blood in one case), hence identifying for the first time the presence of such cells within a living animal. Importantly, we also report a previously undescribed gender difference in the phenotype of the preleukemic cells and leukemia, suggesting a gender imbalance in the radiation-induced leukemic target cell. In conclusion, we provide novel insights into the sequence of molecular events occurring during the (radiation-induced) leukemic clonal evolution.

Interstitial Deletion of Chromosome 9q in Therapy-Related Acute Promyelocytic Leukemia with Pathognomonic t(15;17) in a Patient Exposed to Radioactive Iodine

Interstitial Deletion of Chromosome 9q in Therapy-Related Acute Promyelocytic Leukemia with Pathognomonic t(15;17) in a Patient Exposed to Radioactive Iodine

Síndrome 4q- por deleción intersticial 4(Q22Q25) de novo en un neonato a término

Se describe el caso de un neonato a término de sexo masculino con anomalías del desarrollo psicomotor, defectos cráneo-faciales, anomalías de las extremidades y de los genitales, nacido en el Instituto Nacional Materno Perinatal en quien se halló una deleción cromosómica intersticial en el brazo largo del cromosoma 4. El cariotipo del neonato fue 46,XY, del (4) (q22q25) de novo. Los rasgos fenotípicos observados en el propositus fueron compatibles con síndrome 4q- .

Pazopanib therapy for adolescent and young adult desmoid tumors.

10547 Background: There is a lack of reliably effective medical therapies for desmoid tumors (DT). Surgical resection may be morbid, and even a complete resection does not preclude recurrence. Radiotherapy is associated with potentially severe late-effects, a risk that may be particularly detrimental in young patients. In a previous review of our single institution DT experience, we found that objective treatment responses to medical therapies were rare.However,we have recently observed promising effect from therapy with the tyrosine kinase inhibitor pazopanib in adolescent and young adult (AYA) patients with DT. Methods: Retrospective single institution chart review evaluating all pazopanib treatment in AYA patients with DT. Results: Five AYA patients, ages 15-21 years, with previously treated DT received pazopanib. Four patients with sporadic DT were documented by next generation sequencing to have mutations of CTNNB1, and 1 patient with intra-abdominal tumors following colectomy was known to carry a large germline interstitial chromosomal deletion (5q21.2q23.1) including the APC locus. The median duration of pazopanib treatment was 6 months at the time of analysis (range: 5-21), with treatment ongoing for 4 patients. None of the patients demonstrated progressive disease while on treatment. Best responses by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST) were partial response in 3 of 5 and stable disease in 2 of 5 cases. One response was nearly complete. In one case of stable disease, tumor necrosis was evident on magnetic resonance imaging after 2 months on pazopanib. Four patients reported pain relief while on pazopanib, including one patient with stable disease. Pazopanib was discontinued in 1 patient after 18 months due to recurrent facial edema. Other grade 1-2 adverse effects responded to dose reduction. The only grade 3 adverse effect was increasing weakness in a patient with pre-existing myopathy; this patient tolerated pazopanib at a reduced dose. Conclusions: This is the first report of objective responses to pazopanib by RECIST criteria in AYA patients with DT. Given these benefits and relatively mild toxicity, we conclude that pazopanib therapy should be considered in this patient population.

A Case of Congenital Hypopituitarism Associated With a 1p31 Microdeletion: A Possible Role for LEPR and JAK1

Context:Genetic defects affecting the expression and function of factors involved in pituitary development have been found to be associated with congenital hypopituitarism (CH). However, for most cases of CH, the etiology remains unknown.Case Description:We present an unusual case of an infant with CH, associated with septo-optic dysplasia with an absent anterior pituitary and an ectopic posterior pituitary gland, resulting from a de novo 8.04-Mb interstitial deletion of chromosome 1p31.1-1p31.3. The deleted region includes several genes that might be involved in pituitary development, including LEPR and JAK1.Conclusions:Haploinsufficiency of LEPR and/or JAK1 might be associated with CH. This finding suggests a role for LEPR-mediated glycoprotein 130 signaling in human pituitary development.

NEIL1 is a candidate gene associated with common variable immunodeficiency in a patient with a chromosome 15q24 deletion

We report the first patient with an interstitial deletion of chromosome 15q24.1-q24.3 associated with common variable immunodeficiency (CVID). The 18-year old female patient's clinical and immunological phenotype was compared with 8 additional previously published patients with chr15q24 deletions. A CGH analysis estimated the deletion to be 3.767Mb in size (chr15: 74,410,916–78,178,418) and the result was confirmed using qRT-PCR. We defined an immune-related commonly deleted region (ICDR) within the chromosomal band 15q24.2, deleted in all four patients with different forms of antibody deficiencies. Mutations in the 14 genes within this ICDR were not identified in the remaining allele in our patient by WES and gene expression analyses showed haploinsufficiency of all the genes. Among these genes, we consider Nei Like DNA Glycosylase 1 (NEIL1) as a likely candidate gene due to its crucial role in B-cell activation and terminal differentiation.

Deleción 17p11.2 en una niña dismórfica con evidencia fenotípica de síndrome de smith-magenis y una revisión de la literatura

Las deleciones cromosómicas son anomalías estructurales que originan pérdidas del material genómico ydependiendo de su extensión suelen dar lugar a condiciones genéticas irreversibles muy discapacitantes. Ladeleción intersticial del brazo corto del cromosoma 17 en la región 17p11.2 está relacionada a la aparición decaracterísticas fenotípicas comunes a una condición genética conocida como Síndrome de Smith-Magenis. Ladeleción, en un rango que varía entre &lt;1.5 Mb y 9 Mb se manifiesta con dismorfias craneofaciales, retardo enel desarrollo psicomotor, problemas del habla, trastornos del sueño, anomalías de las extremidades, ademásde malformaciones cerebrales, cardiacas y renales. Reportamos el caso de una niña de 10 meses, conbraquicefalia, frente abombada, ojos hundidos, pliegues epicánticos, orejas malformadas, philtrum corto, bocapequeña, laringomalacia, trastornos del sueño y ventriculomegalia. El cariotipo de la niña fue 46,XX, del (17)(p11.2), no se realizaron pruebas moleculares por no estar disponibles, pero por las evidencias fenotípicas, losaspectos clínicos y citogenéticos clásicos, se propone un cuadro de Síndrome de Smith-Magenis. Sugerimosel seguimiento del caso y ejecución de pruebas moleculares modernas para un diagnóstico definitivo.