Multiple Congenital Anomalies and Global Developmental Delay in a Patient with Interstitial 6q25.2q26 Deletion: A Diagnostic Odyssey

2018 ◽  
Vol 156 (4) ◽  
pp. 191-196
Author(s):  
Prabakaran Paulraj ◽  
Janice C. Palumbos ◽  
Amanda Openshaw ◽  
John C. Carey ◽  
Reha M. Toydemir
Keyword(s):  
Congenital Anomalies ◽  
Chromosomal Abnormalities ◽  
Genetic Disorder ◽  
Deletion Syndrome ◽  
Growth Delay ◽  
Global Developmental Delay ◽  
Loss Of Function ◽  
Multiple Congenital Anomalies ◽  
Microdeletion Syndromes ◽  
Cornelia De Lange

Interstitial deletions involving 6q25 are rare chromosomal abnormalities associated with distinctive phenotypic features. We describe a 9-year-old boy who was followed from his infancy due to his multiple congenital anomalies and complex medical history. Over the years, a number of diagnoses were considered including Cornelia de Lange syndrome, Rubinstein-Taybi syndrome, as well as “a novel genetic disorder.” Various genetic tests, including a BAC-based array-CGH analysis, were reported as normal. Recently, a SNP-based microarray analysis was performed and showed an 11.1-Mb deletion from 6q25.2 to 6q26, including ARID1B and ZDHHC14. Recent literature suggests that the 6q25 deletion syndrome is a recognizable entity characterized by growth delay, developmental disabilities, microcephaly, hearing loss, and variable other malformations including cleft palate. These features overlap with those of Coffin-Siris syndrome, which is caused by deletions and loss-of-function mutations of ARID1B. Retrospectively, this patient has features resembling both Coffin-Siris and 6q25 microdeletion syndromes.

scholarly journals First-Tier Array CGH in Clinically Variable Entity Diagnosis: 22q13.3 Deletion Syndrome

2020 ◽  
Author(s):  
Magdalena Budisteanu ◽  
Andreea Tutulan-Cunita ◽  
Ina Ofelia Focsa ◽  
Sorina Mihaela Papuc ◽  
Aurora Arghir
Keyword(s):  
Copy Number ◽  
Genetic Disorder ◽  
Mutation Screening ◽  
Pathogenic Mutation ◽  
Deletion Syndrome ◽  
Chromosomal Microarray ◽  
Loss Of Function ◽  
Clear Cut ◽  
Diagnostic Approaches ◽  
Next Generation Sequencing Ngs

Phelan-McDermid (PMS) or 22q13 deletion syndrome (OMIM 606232) is a rare genetic disorder with highly variable clinical presentation. The phenotype includes generalized neonatal hypotonia, developmental delay with intellectual disability and delayed speech, mild dysmorphic features, and autistic behavior. The genetic defects of PMS consist of 22q13.3 deletions or chromosomal structural rearrangements involving SHANK3 gene; the loss of function mutations of SHANK3 gene was reported in a minority of cases. The 22q13.3 deletions vary in size, from 0.2 to over 9 Mb, and, although larger deletions are generally associated with more severe phenotypes, the genotype-phenotype correlations are not clear-cut for all patients. SHANK3 is considered the main candidate gene for the neurologic features of PMS. PMS is a rare disorder, often underdiagnosed. There are no established clinical diagnostic criteria for PMS. The genetic tests typically used are chromosomal microarray and multiplex ligation-dependent probe amplification (MLPA) or fluorescent in situ hybridization (FISH) for copy number analysis of SHANK3 gene; next-generation sequencing (NGS) or Sanger sequencing is used for pathogenic mutation screening of SHANK3. In this chapter, we report three cases with PMS and summarize the clinical and genetic diagnostic approaches of this condition, highlighting the role of chromosomal microarray technology in the identification of rare, but significantly impacting patient’s life, DNA copy number abnormalities.

scholarly journals Homozygous noncanonical splice variant in LSM1 in two siblings with multiple congenital anomalies and global developmental delay

2019 ◽  
Vol 5 (3) ◽  
pp. a004101 ◽  
Author(s):  
Volkan Okur ◽  
Charles A. LeDuc ◽  
Edwin Guzman ◽  
Zaheer M. Valivullah ◽  
Kwame Anyane-Yeboa ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Congenital Anomalies ◽  
Splice Variant ◽  
Global Developmental Delay ◽  
Multiple Congenital Anomalies

scholarly journals Genetic Analysis Algorithm for the Study of Patients with Multiple Congenital Anomalies and Isolated Congenital Heart Disease

Proceedings ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 8
Author(s):  
Marisol Delea ◽  
Lucía Massara ◽  
Lucía Espeche ◽  
María Bidondo ◽  
Pablo Barbero ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Anomalies ◽  
Congenital Heart ◽  
Diagnostic Yield ◽  
Copy Number Variations ◽  
Public Hospitals ◽  
Deletion Syndrome ◽  
Comparative Genomic ◽  
Multiple Congenital Anomalies

In this work, we aim to identify the genetic causes of pathogenesis in Argentinean patients with multiple congenital anomalies (MCA) and isolated Congenital Heart Disease (iCHD). We recruited 174 MCA and 194 iCHD patients from 15 public hospitals. Karyotyping was performed for MCA patients, and MLPA for conotruncal CHD or suspected 2q11 Deletion Syndrome (22q11DS). Selected samples were analyzed by array-CGH (Comparative genomic hybridization) (n = 89) and/or Next-Generation Sequencing (NGS) (n = 18). We successfully analyzed 252/368 patients: 14 had cytogenetic abnormalities, 27 had imbalances in 22q11, and 16 had other clinically relevant copy number variations (CNVs). NGS revealed 12 relevant nucleotide variants (five novels). Combining molecular, clinical and genetic evaluations, the diagnostic yield was 26.2%.

scholarly journals A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Poh Hui Chia ◽  
Franklin Lei Zhong ◽  
Shinsuke Niwa ◽  
Carine Bonnard ◽  
Kagistia Hana Utami ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Germline Mutation ◽  
Growth Delay ◽  
Global Developmental Delay ◽  
Loss Of Function ◽  
C Elegans ◽  
Calcium Calmodulin Dependent ◽  
Severe Intellectual Disability

Calcium/calmodulin-dependent protein kinase II (CAMK2) plays fundamental roles in synaptic plasticity that underlies learning and memory. Here, we describe a new recessive neurodevelopmental syndrome with global developmental delay, seizures and intellectual disability. Using linkage analysis and exome sequencing, we found that this disease maps to chromosome 5q31.1-q34 and is caused by a biallelic germline mutation in CAMK2A. The missense mutation, p.His477Tyr is located in the CAMK2A association domain that is critical for its function and localization. Biochemically, the p.His477Tyr mutant is defective in self-oligomerization and unable to assemble into the multimeric holoenzyme.In vivo, CAMK2AH477Y failed to rescue neuronal defects in C. elegans lacking unc-43, the ortholog of human CAMK2A. In vitro, neurons derived from patient iPSCs displayed profound synaptic defects. Together, our data demonstrate that a recessive germline mutation in CAMK2A leads to neurodevelopmental defects in humans and suggest that dysfunctional CAMK2 paralogs may contribute to other neurological disorders.

scholarly journals Trauma due to Self-aggression in Patient with Waardenburg Syndrome associated with Congenital Anomalies

2016 ◽  
Vol 17 (8) ◽  
pp. 702-705 ◽  
Author(s):  
Sara Nader Marta ◽  
Roberto Yoshio Kawakami ◽  
Claudia Almeida Prado Piccino Sgavioli ◽  
Ana Eliza Correa ◽  
Guaniara D’Árk de Oliveira El Kadre ◽  
...  
Keyword(s):  
Congenital Anomalies ◽  
Autosomal Dominant ◽  
Lateral Displacement ◽  
Genetic Disorder ◽  
Dental Morphology ◽  
Waardenburg Syndrome ◽  
Multiple Congenital Anomalies ◽  
Sacred Heart ◽  
Self Mutilation ◽  
Variable Penetrance

ABSTRACT Waardenburg syndrome (WS) is an inherited autosomal dominant genetic disorder presenting variable penetrance and expressivity, with an estimated prevalence of 1:42,000. Clinical characteristics of WS include lateral displacement of the internal eye canthus, hyperplasia of the medial portion of the eyebrows, prominent and broad nasal base, congenital deafness, pigmentation of the iris and skin, and white forelock. A 24-year-old male patient, previously diagnosed with WS, was referred to the Special Needs Dental Clinic of Sacred Heart University, Bauru, Brazil. Parents reported that the patient was experiencing self-mutilation, particularly in the oral region. He presented multiple congenital anomalies, including anophthalmia, mental retardation, low-set ears, and leg deformities. Clinical oral examination revealed hypodontia, abnormalities in dental morphology, extensive dental caries, periodontal disease, and fistulae. Extensive scars on the tongue, lips, and hands caused by self-mutilation were also observed. In accordance with his family and neurologist, full-mouth extraction under general anesthesia was performed, especially considering his severe self-aggressive behavior and the necessity to be fed with soft-food diet due to his inability to chew. After the surgical procedure, a significant reduction in the patient's irritability and gain of weight were reported in the followups of 30, 60, and 180 days. How to cite this article Marta SN, Kawakami RY, Sgavioli CAPP, Correa AE, D’Árk de Oliveira El Kadre G, Carvalho RS. Trauma due to Self-aggression in Patient with Waardenburg Syndrome associated with Congenital Anomalies. J Contemp Dent Pract 2016;17(8):702-705.

scholarly journals Tetrasomy 9p Syndrome in a Filipino Infant

2020 ◽  
Vol 54 (4) ◽  
Author(s):  
Ebner Bon G. Maceda ◽  
Erena S. Kasahara ◽  
Edsel Allan G. Salonga ◽  
Myrian R. Dela Cruz ◽  
Leniza De Castro-Hamoy
Keyword(s):  
Chromosomal Abnormality ◽  
Congenital Anomalies ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Chromosomal Abnormalities ◽  
Chromosome 9 ◽  
Palpebral Fissure ◽  
Facial Features ◽  
Multiple Congenital Anomalies ◽  
Common Features

Tetrasomy 9p syndrome is a rare chromosomal abnormality syndrome whose most common features include hypertelorism, malformed ears, bulbous nose and microretrognathia. These features present as a result of an additional two copies of the short arm of chromosome 9. Here we present a neonate with characteristic facial features of hypertelorism, downslanted palpebral fissure, bulbous nose, small cupped ears, cleft lip and palate, and downturned corners of the mouth. Clinical features were consistent with the cytogenetic analysis of tetrasomy 9p. In general, clinicians are not as familiar with the features of tetrasomy 9p syndrome as that of more common chromosomal abnormalities like trisomies 13, 18, and 21. Hence, this case re-emphasizes the importance of doing the standard karyotyping for patients presenting with multiple congenital anomalies. Also, this is the first reported case of Tetrasomy 9p syndrome in Filipinos

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