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A Rare Presentation of 1q32q42 Associated with a Complex Adverse Phenotype

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical Genetics
  • Secondary Categories:
    • Clinical Genetics
Introduction
Duplications of 1q32q42 are exceedingly rare. Breakpoints and size of the duplication vary, with some cases involving additional chromosomal abnormalities. This complicates delineation of features caused by the abnormality, and reported phenotypes are highly variable. Cognitive impairment is the most common feature seen in those with 1q32q42 duplications. Reported dysmorphic features include wide sutures and fontanelles, flat nasal bridge, downslanting palpebral fissures, prominent forehead, low set, posteriorly rotated, and malformed ears. Medical complications such as low birth weight after intrauterine growth restriction, cardiac defects, central nervous and urogenital anomalies, respiratory infections, seizures, and hearing deficits can also be seen. Given the rarity of this chromosomal abnormality, reported cases give us the opportunity to better define the associated phenotype.

Case Presentation
This patient is a female born by spontaneous vaginal delivery at 40 weeks gestation to a 22-year-old G2P0010 woman. Pregnancy was complicated by maternal hypertension in the third trimester. The father was 22 years old. Antenatal surveillance was reassuring throughout. There was exposure to no suspected teratogens. Birth weight was 3.15 kg (20th percentile), length 48.3 cm (15th percentile), head circumference is not available at this time. Neonatal period was notable for jaundice



At 14 years of age, she is notable for global delays, intellectual disability, and behavioral issues. Diagnoses include ADHD, OCD, Tourette syndrome, and insomnia. Developmental evaluation revealed a full-scale IQ of 44. Dysmorphic features include low-set ears, down-slanting palpebral fissures, epicanthal folds, broad flat nasal tip, hypotonia, dental crowding, and flat feet. Medical complications include dextroscoliosis, hypotonia, osteoporosis, and astigmatism. At 14-years-old, height is 1.435m (< 1st percentile), although head circumference is 54.5 cm and weight is 61.2 kg, both within normal ranges.

 

Diagnostic Workup
Karyotype analysis revealed 46,XX,dup(1)(q42q44). SNP microarray revealed microarray revealed a 19.24 Mb duplication of 1q32.2q42. 13. Chromosomal analysis on both parents was normal, suggesting this mutation was de novo or a result of gonadal mosaicism. Brain MRI revealed hypoplastic corpus callosum and hippocampus and an abnormal cingulate gyrus.

Treatment and Management
At 14-years-old, the patient receives occupational therapy and physical therapy. Psychotropic medications have been tried to address behavioral concerns, without success. Genetic counseling included the discussion of limitations of knowledge about the chromosomal duplication given few similar reported cases.

Outcome and Follow-Up
Long-term follow up actions encompass referral to child development with a goal of better defining the adverse phenotype and to establish directed therapeutic efforts. In view of the developmental delays being manifested in this patient, it is imperative that ongoing attention is given to multidisciplinary assessment and intervention, including occupational therapy, physical therapy, speech therapy, and special education to maximize long-term developmental potential.

 

Discussion
The constellation of features seen in this patient can be attributed to her large chromosomal duplication. Further management involves establishing a better definition of the adverse phenotype pertaining to her behavioral issues to establish more goal-directed therapeutic efforts, as well as encouraging multidisciplinary intervention.

Conclusion
A 1q32q42 duplication is a rare chromosomal abnormality with limited available literature to support a consistent constellation of dysmorphic features. This case presents a patient with features comparable to others with similar duplications, though the emergence of additional cases with a similar genetic abnormality would provide a better understanding of clinical course and resources to maximize development.

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