Seven-year follow-up documents partial chromosome 19p duplication

A seven-year follow-up of a boy diagnosed before birth with partial trisomy 19p13.3–p13.2 documents severe developmental delay, growth restriction, microcephaly, hearing loss and feeding problems, alongside variable effects on other organ systems. The case report traces the abnormality from routine antenatal ultrasonography through molecular and chromosome testing, neonatal assessment and childhood follow-up. Researchers identified a 6.83-megabase duplication at the distal short arm of chromosome 19, inherited through an unbalanced product of a maternal balanced reciprocal translocation involving chromosomes 13 and 19. The report says the case is the first published description of partial trisomy 19p13.3–p13.2 resulting from a maternal reciprocal translocation in the Middle East.

Prenatal detection began at 26 weeks of gestation, when ultrasonography showed severe intrauterine growth restriction and marked oligohydramnios. The clinicians performed amniocentesis and chromosomal microarray analysis, which detected a copy-number gain spanning chromosome 19p13.3–p13.2, reported as arr[GRCh37] 19p13.3–p13.2 (260,911_7,089,557)x3. Fetal karyotyping with fluorescence in situ hybridization showed an unbalanced derivative chromosome 13 inherited from the mother. Parental chromosome studies then established that the mother carried an apparently balanced reciprocal translocation, 46,XX,t(13;19)(p12;p13.2). Transmission of an unbalanced derivative chromosome resulted in the fetal duplication. No clinically significant loss of chromosome 13 material was detected, indicating that the principal genomic imbalance was the extra copy of the 19p segment.

Following genetic counseling about the prenatal findings, the uncertain prognosis and available pregnancy options, the parents elected to continue the pregnancy. Serial ultrasound throughout the remainder of the gestation showed persistent fetal growth restriction, and the umbilical cord contained a single umbilical artery. The infant was born spontaneously at 38 weeks with a weight of 1,110 grams, consistent with severe growth restriction. He developed respiratory distress shortly after delivery, required high-flow nasal cannula support and nasogastric feeding, and spent 11 days in a neonatal intensive care unit. Examination revealed microcephaly, a soft and enlarged fontanelle, sparse arched eyebrows, widely spaced eyes with upslanting palpebral fissures, low-set ears, a prominent nose, a long smooth philtrum, thin lips and mild microretrognathia.

Neonatal investigations identified several abnormalities beyond the chromosomal diagnosis. Cranial ultrasonography found a small left choroid plexus cyst without other structural brain parenchymal abnormalities, and the cyst resolved by six months. An abnormal newborn hearing screen was followed by auditory brainstem response testing two weeks later, which showed mild-to-moderate bilateral conductive hearing loss. Renal ultrasonography detected mild left hydronephrosis, while voiding cystourethrography showed vesicoureteral reflux, graded III on the left and I on the right. Echocardiography did not reveal a structural cardiac abnormality. These findings showed that the phenotype extended beyond growth and neurodevelopment to hearing and urinary tract function, although not every system commonly reported in chromosome 19p duplications was affected.

Feeding problems began immediately and continued after discharge. The boy required nasogastric tube feeding throughout his neonatal intensive care admission and for approximately two additional months, and later formal assessment confirmed dysphagia with both solids and liquids. Gastroesophageal reflux disease developed during infancy and was treated with metoclopramide for about two years. His growth remained poor, and at seven years his weight, height and head circumference were all below the third centile. He experienced recurrent febrile seizures from infancy until about age five, leading to multiple hospital admissions, although serial electroencephalograms were normal and long-term antiseizure medication was not required. Brain magnetic resonance imaging and computed tomography showed no structural brain abnormalities. Mild lower-limb spasticity became apparent at age four, and persistent sleep disturbances occurred despite normal polysomnography.

Global developmental delay affected all domains. The child achieved head control at approximately five months, independent sitting at 16 months, rolling from prone to supine at 18 months and independent walking at three years. He could reach for and transfer objects by about nine months but had not developed a mature pincer grasp by age seven. Language development was especially limited: he continued to vocalize and babble during play but had not developed intelligible speech, relying mainly on gestures such as pointing. Social development was also substantially affected, with poor eye contact, inconsistent responses to caregivers, limited comprehension of verbal commands and frequent behavioral outbursts, including head banging when frustrated. At his latest assessment, he remained nonverbal and required full assistance with feeding, dressing, hygiene and toileting. Neurological examination showed axial hypotonia with mild appendicular spasticity, and he continued to receive speech and language, occupational and physiotherapy support.

Other childhood complications included recurrent otitis media requiring tympanostomy tubes, subsequent chronic otomycosis and a soft cleft palate with a bifid uvula identified at age four. Bilateral positional congenital foot deformities were managed successfully with orthoses over three years. The boy also had recurrent urinary tract infections during early childhood. His vesicoureteral reflux and hydronephrosis resolved spontaneously by age three, and urinary infections became less frequent after circumcision. The investigators described these findings as evidence of a broad but variable multisystem phenotype. Their literature review, restricted to published pure, non-mosaic chromosome 19p duplications for closer comparison, found that neurodevelopmental impairment was the most consistent feature among previously reported patients.

The comparison also highlighted important differences. Growth restriction, microcephaly and craniofacial features—including hypertelorism, low-set ears and philtral abnormalities—recurred in people with overlapping duplications and were present in this boy. In contrast, cardiac defects had appeared in several earlier patients but were absent here, while musculoskeletal findings ranged from hypotonia to major limb and skeletal abnormalities. Conductive or sensorineural hearing loss and recurrent ear disease had been described inconsistently. Renal and genitourinary abnormalities, including hydronephrosis and urinary tract abnormalities, were also variable. The case authors therefore emphasized that the recurrent febrile seizures should not automatically be interpreted as epilepsy: the literature describes variable seizure outcomes rather than a universal seizure disorder, and prognosis has to be assessed from each patient’s clinical course.

The authors also reviewed DECIPHER patients whose duplications fell entirely within the affected interval. These cases ranged from several kilobases to more than four megabases and showed marked clinical variability. Developmental delay was the most frequently reported feature, while autism spectrum disorder, intellectual disability, feeding difficulties, failure to thrive, craniofacial abnormalities and short stature occurred only in subsets of patients. Some people with relatively small duplications had developmental or isolated neurodevelopmental findings, whereas others with larger gains had involvement of growth, hearing, craniofacial development, gastrointestinal function and the urinary tract. The findings suggest that genomic overlap alone does not fully explain severity. Gene content, breakpoint position, the rearrangement mechanism, inheritance pattern and possible genetic or environmental modifiers may all contribute, and the available evidence does not establish a single critical region or a robust relationship between duplication size and clinical outcome.

Gene-level review identified multiple candidates within the duplicated segment but did not establish any one of them as causal. DOT1L, SEMA6B, KDM4B and DOHH are associated with neurodevelopmental disorders; TUBB4A with neurological disorders including hypomyelination with atrophy of the basal ganglia and cerebellum; FZR1 with intellectual disability and epilepsy; and LMNB2 with a disorder that includes microcephaly. Other genes in the interval have associations involving hearing, mitochondrial function, immune function and hematological disease. Among 51 morbid genes analyzed, 21 had pTriplo scores of at least 0.68, and nine scored at least 0.94: TUBB4A, MAP2K2, CLPP, DPP9, FZR1, GPX4, EEF2, KDM4B and AP3D1. These scores predict sensitivity to copy-number gain rather than demonstrate pathogenicity. ClinGen has not established definitive triplosensitivity for the candidate genes, and some disease associations involve loss-of-function or biallelic mechanisms rather than increased dosage. The phenotype may therefore reflect a combined dosage effect across multiple genes, but the single-patient design cannot demonstrate that explanation.

The report’s main strength is its integration of antenatal diagnosis, microarray-defined duplication, cytogenetic characterization of the maternal translocation and longitudinal observation through age seven. Its limitations are equally clear: one case cannot establish causality, and comparisons with previous reports are constrained by different duplication sizes, breakpoint resolutions, genomic methods, associated rearrangements and inconsistent clinical reporting. DECIPHER analyses are further affected by incomplete information and ascertainment bias. Nevertheless, the case demonstrates why chromosomal microarray and conventional karyotyping are complementary: microarray defines the copy-number imbalance, while parental cytogenetics identifies the inherited rearrangement that created it. The findings support individualized counseling for families, with uncertainty explicitly discussed, parental chromosome testing used to characterize the mechanism and long-term multidisciplinary follow-up arranged for children with distal 19p duplications.

Subject of Research: Clinical and molecular features of partial chromosome 19p trisomy in a seven-year-old boy

Article Title: Partial trisomy 19p13.3-p13.2 from antenatal diagnosis to 7-year follow-up: case report and literature review

Article References: Abualnaja, R., Azher, Z., Alkhaifi, S., & Alkharouby, R. (2026). Partial trisomy 19p13.3-p13.2 from antenatal diagnosis to 7-year follow-up: case report and literature review. Frontiers in Genetics, 17, Article 1869055. https://doi.org/10.3389/fgene.2026.1869055

Image Credits: AI Generated

DOI: 10.3389/fgene.2026.1869055

Keywords: partial trisomy 19p, chromosome 19p duplication, prenatal diagnosis, reciprocal translocation, developmental delay, microcephaly, chromosomal microarray, DECIPHER, genetic counseling, Partial, trisomy, antenatal