PTCH1 duplication in a family with microcephaly and mild developmental delay

The clinical implications of venous cerebrovascular maldevelopment remain poorly understood. We report on the association of cerebrofacial venous anomalies (including sinus pericranii), ocular abnormalities and mild developmental delay in two children. In addition, one child had a seizure disorder. Complex cerebrofacial slow-flow vascular anomalies may herald an underlying developmental aberration affecting the cerebrofacial and orbital regions.

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MEIS2 (15q14) gene deletions in siblings with mild developmental phenotypes and bifid uvula: documentation of mosaicism in an unaffected parent

Molecular Cytogenetics ◽

10.1186/s13039-021-00570-1 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Bin Zhang ◽

Michel Liu ◽

Chin-To Fong ◽

M. Anwar Iqbal

Keyword(s):

Developmental Delay ◽

Cleft Lip ◽

Point Mutations ◽

Recurrence Risk ◽

Gene Deletions ◽

Genomic Deletion ◽

Mild Developmental Delay ◽

Cleft Lip Palate ◽

Transcription Regulators ◽

Unaffected Parent

AbstractMEIS2 (Meis homeobox 2) encodes a homeobox protein in the three amino acid loop extension (TALE) family of highly conserved homeodomain-containing transcription regulators important for development. MEIS2 deletions/mutations have been associated with cleft lip/palate, dysmorphic facial features, cardiac defects, as well as intellectual disability at a variable severity. Here we report on one familial case that two affected siblings carry the same non-mosaic ~ 423 kb genomic deletion at 15q14 encompassing the entirety of CDIN1 and the last three exons (ex. 10, 11, 12) of the MEIS2 gene, while their unaffected father is mosaic for the same deletion in about 10% lymphocytes. Both siblings presented with mild developmental delay and bifid uvula, while no congenital cardiac abnormalities were identified. The elder sister also showed syncopal episodes and mild speech delay and the father had atrial septal defects. This is the first report showing multiple family members inherit a genomic deletion resulting in a MEIS2 partial truncation from a mosaic parent. Taken all together, this study has important implications for genetic counseling regarding recurrence risk and also points to the importance of offering MEIS2 gene tests covering both point mutations and microdeletions to individuals with milder bifid uvula and developmental delay.

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A 4-year-old girl with mild developmental delay and a history of confusion and abnormal night-time movements of her extremities

Case Studies in Polysomnography Interpretation ◽

10.1017/cbo9781139058490.080 ◽

2015 ◽

pp. 94-94

Author(s):

Irina Ok ◽

Alcibiades Rodriguez

Keyword(s):

Developmental Delay ◽

Night Time ◽

Mild Developmental Delay ◽

History Of

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Sulfonylurea-insensitive permanent neonatal diabetes caused by a severe gain-of-function Tyr330His substitution in Kir6.2

Hormone Research in Paediatrics ◽

10.1159/000521858 ◽

2022 ◽

Author(s):

Conor McClenaghan ◽

Novella Rapini ◽

Domenico Umberto De Rose ◽

Jian Gao ◽

Jacob Roeglin ◽

...

Keyword(s):

Developmental Delay ◽

Molecular Basis ◽

Glucose Monitoring ◽

Neonatal Diabetes ◽

Katp Channels ◽

Gain Of Function ◽

Gene Encoding ◽

Permanent Neonatal Diabetes ◽

Mild Developmental Delay ◽

Atp Inhibition

Background/Aims: Mutations in KCNJ11, the gene encoding the Kir6.2 subunit of pancreatic and neuronal KATP channels, are associated with a spectrum of neonatal diabetes diseases. Methods: Variant screening was used to identify cause of neonatal diabetes, and continuous glucose monitoring used to assess effectiveness of sulfonylurea treatment. Electrophysiological analysis of variant KATP channel function was used to determine molecular basis. Results: We identified a previously uncharacterized KCNJ11 mutation, c.988T>C [pTyr330His], in an Italian child diagnosed with sulfonylurea-resistant permanent neonatal diabetes and developmental delay (iDEND). Functional analysis of recombinant KATP channels reveals that this mutation causes a drastic gain-of-function, due to a reduction in ATP-inhibition. Further, we demonstrate that the Tyr330His substitution causes a significant decrease in sensitivity to the sulfonylurea, glibenclamide. Conclusions: In this subject, the KCNJ11(c.988T>C) mutation provoked neonatal diabetes, with mild developmental delay, which was insensitive to correction by sulfonylurea therapy. This is explained by the molecular loss of sulfonylurea sensitivity conferred by the Tyr330His substitution, and highlights the need for molecular analysis of such mutations.

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The Management of Birth-Related Posterior Fossa Hematomas in Neonates

Neurosurgery ◽

10.1227/neu.0b013e318286fc3a ◽

2013 ◽

Vol 72 (5) ◽

pp. 755-762 ◽

Cited By ~ 8

Author(s):

Thomas Blauwblomme ◽

Matthew Garnett ◽

Estelle Vergnaud ◽

Nathalie Boddaert ◽

Marie Bourgeois ◽

...

Keyword(s):

Developmental Delay ◽

Posterior Fossa ◽

Ventriculoperitoneal Shunt ◽

Case Series ◽

External Ventricular Drainage ◽

Cranial Ultrasound ◽

Delayed Presentation ◽

Mild Developmental Delay ◽

Brainstem Dysfunction

Abstract BACKGROUND: Symptomatic posterior fossa hematoma in the term newborn is rare. OBJECTIVE: To report on the management and outcome of posterior fossa subdural hematoma (PFSDH) in neonates. METHODS: A retrospective analysis of the department database and clinical notes of neonates admitted since 1985 with a PFSDH was performed together with a literature review of similar case series. RESULTS: Sixteen patients were included. The median gestational age was 40 weeks with a high proportion of primiparous mothers (n = 9) and forceps delivery (n = 9). Nine neonates had symptoms of brainstem dysfunction within the first 24 hours of life, whereas the other 7 had a delayed presentation (median 4 days) with signs of raised intracranial pressure due to hydrocephalus. Each patient had a cranial ultrasound followed by computed tomography scan that showed the PFSDH. Eleven neonates required surgical evacuation of the PFSDH, whereas hydrocephalus was managed by transient external ventricular drainage in 2 further patients. Eventually, 2 neonates required a permanent ventriculoperitoneal shunt. Five neonates had no operative intervention. With a mean follow-up of 7.8 years, 2 patients had mild developmental delay and 1 had severe developmental delay. The 13 other patients had a normal development. CONCLUSION: In neonates with a PFSDH, surgery can be safely performed in those who have clinical and radiological signs of brainstem compression or hydrocephalus. A small number of neonates require a ventriculoperitoneal shunt in the long term. Initial aggressive resuscitation should be performed even in cases of initial severe brainstem dysfunction because of the good long-term neurological outcome.

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