Neurology
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
Causes of unilateral ptosis include: Congenital – may be associated with dysmorphic features.Horner syndrome (Figs 8.4–8.7). Third nerve palsy (Figs 8.8, 8.9). The ptosis is usually severe (8.9). In a complete third nerve palsy (8.8), there is associated dilatation of the pupil and the eye will be positioned ‘down and out’, due to involvement of the superior, inferior and medial rectus and the inferior oblique muscles. See ‘Eye movements’, page 203, for causes. Marcus–Gunn jaw winking (Figs 8.10, 8.11).
Dysmorphology and genetic syndromes
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
In case any reader should think that these scientific developments make clinical skills redundant, it should be emphasised that the reverse is the case. It is only possible to use the new laboratory approaches effectively by using an effective combination of (1) targeting appropriate panels of genes for analysis, where this is most likely to yield a diagnosis without generating too many distracting variants of uncertain significance (VUSs) and incidental findings (IFs) and (2) whole exome or whole genome approaches (array comparative genomic hybridisation [aCGH], whole exome sequencing [WES], WGS) where targeted analyses are unlikely to be fruitful. Furthermore, familiarity with the clinical features of many disorders and a careful clinical examination conducted with sensitivity will often be needed to come to a judgement as to whether a specific genetic variant is likely to have led to the particular phenotype observed. However, the contribution of the clinical geneticist to the care of patients with dysmorphic features is certainly changing as more children have molecular investigations performed before being referred for a clinical genetics assessment.
Endocrinology
Timothy G Barrett, Anthony D Lander, Vin Diwakar in A Paediatric Vade-Mecum, 2002
The following questions need to be asked. Were antenatal USS normal?Are there affected siblings or cousins?Is there consanguinity?On examination, you should be able to describe what you see to your consultant on call. Look for evidence of a phallus.Where is the urethral opening? At the tip of the phallus, somewhere along its length, at the base, or not visible?Are there labioscrotal folds rather than labia or a scrotum?Check the groin for palpable gonads.Is there a separate anus or one cloacal opening?Are there any other dysmorphic features that may suggest a syndrome?
Foetal phenotype of ALG1-CDG caused by paternal uniparental disomy 16
Published in Journal of Obstetrics and Gynaecology, 2021
Ya-Li Lei, Li Zhen, Li-Li Xu, Yan-Dong Yang, Dong-Zhi Li
The type of CDG depends on which enzyme is involved. ALG1-CDG belongs to the five most common CDG disorders along with PMM2-CDG, ALG6-CDG, MPI-CDG and SRD5A3-CDG. Its phenotype is characterised by a predominant neurological involvement. Other dysmorphic features are reported in postnatal patients (Ng et al. 2016). Up to now, only one family of ALG1-CDG has been detected prenatally. A Dutch family experienced recurrent nonimmune hydrops fetalis in their two consecutive pregnancies, with one foetus at 32 weeks and the other at 30 weeks (Schwarz et al. 2004). Only the second patient was tested for ALG1 gene, and confirmed to have the homozygous c.773C > T variant, inherited from his heterozygous parents. The present foetus was another prenatal case with the same ALG1 variant, characterised by an increased NT and asymmetric IUGR. This provides additional information on the prenatal phenotypes of ALG1-CDG, especially for the homozygous c.773C > T variant.
Co-occurring medical conditions among individuals with ASD-associated disruptive mutations
Published in Children's Health Care, 2020
Evangeline C. Kurtz-Nelson, Jennifer S. Beighley, Caitlin M. Hudac, Jennifer Gerdts, Arianne S. Wallace, Kendra Hoekzema, Evan E. Eichler, Raphael A. Bernier
Reflecting the presence of dysmorphic features and congenital anomalies, several gene groups were uniquely characterized by physical and structural abnormalities. Macrocephaly was most strongly associated with PPP2R5D, which is consistent with the hypothesis that mutations in this gene contribute to overgrowth (Shang et al., 2016). DYRK1A was strongly associated with microcephaly, which reflects this gene’s role in neurogenesis and brain growth (Evers et al., 2017). Elevated rates of cardiac problems in ADNP and PACS1, genital problems in PACS1 and SETBP1, and vision problems in ADNP, ARID1B, and DYRK1A highlight the impact of ASD-risk genes on multiple organ systems and overall development. Exploratory analyses also indicated other gene groups that may be at risk for additional co-occurring conditions. For example, cardiac problems were reported for 42.3% of individuals with mutations in DYRK1A, and vision problems were reported for 87.5% of individuals with MED13L mutations; these rates are higher than reported in published literature reviews (Luco et al., 2016; Tørring et al., 2019). Finally, major surgical history appeared to be elevated across groups, which could reflect the presence of structural abnormalities or other medical concerns requiring intensive medical treatment.
A Dysmorphology Based Systematic Approach Toward Perinatal Genetic Diagnosis in a Fetal Autopsy Series
Published in Fetal and Pediatric Pathology, 2018
Shagun Aggarwal, Ashwani Tandon, Aneek Das Bhowmik, Jamal Mohamed Nurul Jain Safarulla, Ashwin Dalal
Dysmorphological evaluation by a clinical geneticist, where soft dysmorphic features and characteristic constellation of abnormalities act as important diagnostic handles, plays an important role in the ascertainment of a genetic diagnosis in the outpatient clinic setting. The use of a similar approach in this study showed a high diagnostic yield of dysmorphology as a standalone evaluation in a postmortem fetal cohort. A definitive genetic diagnosis could be made in 16 and a possible diagnosis in 31, of which 11 could be confirmed by subsequent evaluations. Dysmorphology findings also guided further targeted genetic testing as well as interpretation of histopathology findings in at least 7 of these. The utility of fetal dysmorphology has been indicated by other authors in literature (20,33,34).
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