Intellectual disability associated with craniofacial dysmorphism, cleft palate, and congenital heart defect due to a de novo MEIS2 mutation: A clinical longitudinal study

Many studies have shown that molecular karyotyping is an effective diagnostic tool in individuals with developmental delay/intellectual disability. We report on a de novo interstitial 1q22q23.1 microdeletion, 1.6 Mb in size, detected in a patient with short stature, microcephaly, hypoplastic corpus callosum, cleft palate, minor facial anomalies, congenital heart defect, camptodactyly of the 4-5th fingers, and intellectual disability. Chromosomal microarray analysis revealed a 1.6-Mb deletion in the 1q22q23.1 region, arr[GRCh37] 1q22q23.1(155630752_157193893)×1. Real-time PCR analysis confirmed its de novo origin. The deleted region encompasses 50 protein-coding genes, including the morbid genes APOA1BP, ARHGEF2, LAMTOR2, LMNA, NTRK1, PRCC, RIT1, SEMA4A, and YY1AP1. Although the unique phenotype observed in our patient can arise from the haploinsufficiency of the dosage-sensitive LMNA gene, the dosage imbalance of other genes implicated in the rearrangement could also contribute to the phenotype. Further studies are required for the delineation of the phenotype associated with this rare chromosomal alteration and elucidation of the critical genes for manifestation of the specific clinical features.

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A de novo 0.63 Mb 6q25.1 deletion associated with growth failure, congenital heart defect, underdeveloped cerebellar vermis, abnormal cutaneous elasticity and joint laxity

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.37118 ◽

2015 ◽

Vol 167 (9) ◽

pp. 2042-2051 ◽

Cited By ~ 6

Author(s):

Vincenzo Salpietro ◽

Martino Ruggieri ◽

Kshitij Mankad ◽

Gabriella Di Rosa ◽

Francesca Granata ◽

...

Keyword(s):

Congenital Heart Defect ◽

Congenital Heart ◽

De Novo ◽

Growth Failure ◽

Joint Laxity ◽

Cerebellar Vermis ◽

Heart Defect

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15q26 deletion in a patient with congenital heart defect, growth restriction and intellectual disability: case report and literature review

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01121-5 ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Yahya Benbouchta ◽

Nicole De Leeuw ◽

Saadia Amasdl ◽

Aziza Sbiti ◽

Dominique Smeets ◽

...

Keyword(s):

Intellectual Disability ◽

Developmental Delay ◽

Candidate Genes ◽

Congenital Heart Defect ◽

Cytogenetic Analysis ◽

Congenital Heart ◽

Clinical Manifestations ◽

Growth Restriction ◽

Septal Defects ◽

Heart Defect

Abstract Background 15q26 deletion is a relatively rare chromosomal disorder, and it is described only in few cases. Patients with this aberration show many signs and symptoms, particularly pre- and postnatal growth restriction, developmental delay, microcephaly, intellectual disability and various congenital malformations. Case presentation We report on a girl, 4 years old, of consanguineous parents, with a 15q26 deletion. Clinical manifestations included failure to thrive, developmental delay, microcephaly, dysmorphic facies with broad forehead, hypertelorism, narrowed eyelid slits and protruding columella. The patient also showed skeletal abnormalities, especially clinodactyly of the 5th finger, varus equine right foot and left club foot. Additionally, she had teething delay and divergent strabismus. Heart ultrasound displayed two atrial septal defects with left-to-right shunt, enlarging the right cavities. Routine cytogenetic analysis revealed a shortened 15q chromosome. Subsequent array analysis disclosed a terminal 9.15 Mb deletion at subband 15q26.1-q26.3. Four candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, CHD2 and MEF2A. Conclusion We report on an additional case of 15q26 monosomy, characterized by array-CGH. Molecular cytogenetic analysis allowed us to identify the exact size of the deletion, and four candidate genes for genotype-phenotype correlation. 15q26 monosomy should be considered when growth retardation is associated with hearing anomalies and congenital heart defect, especially atrioventricular septal defects (AVSDs) and/or aortic arch anomaly (AAA).

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MALFORMATIONS AND LEUKEMIA IN CHILDREN WITH DOWN'S SYNDROME

PEDIATRICS ◽

10.1542/peds.45.1.60 ◽

1970 ◽

Vol 45 (1) ◽

pp. 60-70

Author(s):

Jacqueline Fabia ◽

Margaret Drolette

Keyword(s):

Birth Weight ◽

Cleft Palate ◽

Congenital Heart Defect ◽

Imperforate Anus ◽

Duodenal Obstruction ◽

Congenital Heart ◽

Down’S Syndrome ◽

Congenital Megacolon ◽

Heart Defect ◽

The Mean

Among 2,421 children with Down's syndrome born alive to residents of Massachusetts from 1950 through 1966, approximately one-third had at least one malformation other than the characteristic diagnostic criteria of the syndrome itself. After congenital heart defect, the most common were duodenal obstruction, clubfoot, cataract, imperforate anus, syndactyly or webbed fingers and/or toes, cleft palate and/or lip, and congenital megacolon. Males predominated among children with cataract, syndactyly, and congenital megacolon. Somewhat more females than males had congenital heart defect, although the excess was not significant. The mean maternal age was strikingly low for mongols with cleft palate and/or lip and for males with congenital megacolon. The mean birth weight was significantly lower for mongols with malformations, due primarily to a low birth weight of the children with duodenal obstruction. Most malformations occurred more often in combination with other malformations than expected by chance. The exceptions were duodenal obstruction, congenital megacolon, and imperforate anus. Among 23 mongols with leukemia, 5 died in the neonatal period—a very high age-specific leukemia mortality rate. The sex distribution of cases shifted over time from predominantly males to predominantly females. Leukemic mongols weighed somewhat more at birth than other mongols, although not significantly so. The risk of leukemia among mongols was not related to the presence or absence of congenital malformations.

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A novel GATA6 variant in a boy with neonatal diabetes and diaphragmatic hernia: a familial case with a review of the literature

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0057 ◽

2019 ◽

Vol 32 (9) ◽

pp. 1027-1030 ◽

Cited By ~ 1

Author(s):

Odile Gaisl ◽

Daniel Konrad ◽

Pascal Joset ◽

Mariarosaria Lang-Muritano

Keyword(s):

Diaphragmatic Hernia ◽

Congenital Heart Defect ◽

Congenital Heart ◽

De Novo ◽

Heart Defects ◽

Neonatal Diabetes ◽

Short Review ◽

Review Of The Literature ◽

Mild Phenotype ◽

Heart Defect

Abstract GATA6 gene variants come along with possible features such as pancreas agenesis/hypoplasia, neonatal diabetes and congenital heart defect. Congenital hypothyroidism, and hepatobiliary and gut abnormalities are also detectable. Children with congenital heart defects and neonatal diabetes were already described in 1970. GATA6 variants can be due to de novo variants or due to inherited variants. To date, 11 cases due to an inherited variant have been described. Herein we present a novel heterozygous GATA6 variant (c.1291C > T p.[Gln431*]) in a boy with transient neonatal diabetes, diaphragmatic hernia, congenital heart defect and early-onset scoliosis. The same variant was also present in the mother. At the age of 3 years, a random evaluation revealed a hemoglobin A1c (HbA1c) level of 7.8% (62 mmol/mol) without any diabetes-related symptoms. He was started on insulin therapy and HbA1c normalized. A short review of the literature of hereditary cases of the GATA6 variant revealed the variable phenotypic spectrum and showed that patients with a mild phenotype are likely to have children with a more severe phenotype.

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Genetic developmental disability diagnosed in adulthood: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-020-02590-8 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Adam Langenfeld ◽

Lynn Schema ◽

Judith K. Eckerle

Keyword(s):

Intellectual Disability ◽

Developmental Delay ◽

Developmental Disability ◽

Congenital Heart Defect ◽

Congenital Heart ◽

Genetic Counselor ◽

Functional Impairments ◽

Heart Defect ◽

American Patient ◽

History Of

Abstract Background Developmental disabilities (DD) are an umbrella term for conditions associated with functional impairments in physical, learning, language, or behavior areas. Intellectual disability (ID) is a type of developmental disability that results in delays in cognitive or intellectual functioning, such as reasoning, learning, and problem-solving, and adaptive behaviors including social and practical life skills. DD can be due to a variety of factors, ranging from environmental exposures to genetic mutations, and studies suggest that up to 40% of DDs may be caused by genetic issues. Case presentation In this case study, we present an 18-year-old internationally adopted female Chinese American patient with a known history of developmental delay, intellectual disability, strabismus, and a congenital heart defect who had not been tested for genetic causes of her delay prior to presentation. When evaluated with chromosomal microarray, the patient demonstrated a deletion on the short arm of chromosome 5, an area associated with Cri-du-chat syndrome. This chromosomal deletion was a likely explanation for her history of developmental delays, intellectual disability, and congenital heart defect, in addition to her history of institutionalization and the trauma of multiple caregiver transitions in early childhood. The patient was referred for further evaluation by a geneticist and genetic counselor. Conclusions This case highlights that the underlying cause of developmental delay is often multifactorial, and underscores the importance of a full medical evaluation, including genetic testing, for children with intellectual disability. Using this approach, healthcare professionals can identify potential diagnoses and provide more targeted resources to families.

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