Partial duplication of the long arm of chromosome 11 is an uncommon constitutional chromosomal imbalance. Early reports of partial trisomy 11q described recurrent growth impairment, developmental disability, craniofacial dysmorphism, congenital heart disease, and limb abnormalities [1, 2]. Reliable population-based incidence and prevalence figures have not been established; the Orphanet entry for partial duplication of 11q is classified as a group of disorders and does not provide a prevalence estimate [3]. Much of the historical literature concerns distal 11q gains extending to qter, frequently arising as an unbalanced product of a parental translocation [1, 2]. Later reports reinforced the broad association with pre- and postnatal growth restriction, hypotonia, developmental impairment, characteristic facial findings, cardiac defects, and limb anomalies [4]. Consequently, the phenotype of a distal 11q duplication should not be assumed to apply directly to every interstitial 11q gain. Pure interstitial duplications of 11q have been reported far less often and show marked clinical variability. Familial and de novo duplications involving different proximal and mid-11q intervals have been associated with outcomes ranging from developmental delay to essentially normal development [5, 6]. Molecular studies have also shown that chromosome rearrangements that appear similar by banding can differ substantially in genomic boundaries and structural architecture [7-9]. We describe an infant in whom conventional GTG-banded karyotyping demonstrated an interstitial duplication of 11q21–q23. Case Presentation The proband was a 6-month-old boy, the first child of clinically healthy unrelated parents. He was evaluated for persistent poor weight gain, delayed motor milestones, generalized hypotonia, and facial dysmorphism. Maternal and paternal ages at conception were 26 and 30 years, respectively. The family history was negative for congenital malformations, developmental disability, or a similarly affected relative. The pregnancy was conceived spontaneously. Routine ultrasonography in the first two trimesters did not identify a major structural anomaly, but fetal growth deceleration became evident in the third trimester. Delivery was by cesarean section at 37 weeks and 4 days because of a non-reassuring fetal heart-rate pattern. Birth weight was 2.18 kg, length 45 cm, and head circumference 31 cm. The infant cried after stimulation and did not require mechanical ventilation. Feeding was difficult from the neonatal period, with inefficient sucking, prolonged feeds, and easy fatigability. Poor head control and generalized floppiness became apparent by approximately 2 months of age. Between 3 and 5 months of age, he had two brief hospital admissions for cough and tachypnea temporally related to feeding. Feeding assessment suggested mild oropharyngeal incoordination, and conservative feeding measures were advised. At 6 months, social interaction and early receptive responses were relatively preserved: he recognized his parents, smiled responsively, tracked objects, responded to sound, and vocalized. Motor development was more clearly delayed, with incomplete head control, inconsistent rolling, inability to sit with minimal support, and poor truncal tone. There was no history of seizures, developmental regression, or loss of acquired skills. At examination, weight was 5.6 kg, length 61.5 cm, and head circumference 40.2 cm, consistent with generalized growth faltering and microcephaly. Craniofacial features included mild frontal prominence, hypertelorism with epicanthi, a broad mildly depressed nasal bridge, short nose with rounded tip and anteverted nares, long smooth philtrum, thin upper vermilion, mild microretrognathia, and low-set slightly posteriorly rotated ears. The palate was intact. Neurological examination showed generalized hypotonia, more pronounced axially than peripherally, with persistent head lag and reduced truncal resistance. The hands were small with short tapering digits, mildly broad thumbs, and bilateral fifth-finger clinodactyly; the feet were small with mild bilateral forefoot adduction. A soft systolic murmur was audible at the left sternal border. Two-dimensional echocardiography showed an approximately 2.5-mm muscular ventricular septal defect with left-to-right flow, without pulmonary hypertension or clinical heart failure. Abdominal and renal ultrasonography was unremarkable. Neurosonography showed mild prominence of the lateral ventricles without hydrocephalus, intracranial hemorrhage, or major cerebral malformation. Ophthalmological examination was normal. Complete blood count, electrolytes, liver and renal biochemical tests, thyroid profile, calcium, and glucose were appropriate for age. Cytogenetic Analysis Because the infant had growth restriction, hypotonia, developmental delay, dysmorphism, minor limb abnormalities, and a congenital cardiac defect, a constitutional chromosome disorder was considered. Peripheral-blood lymphocytes were cultured for 72 hours in RPMI-1640 medium supplemented with fetal calf serum, L-glutamine, antibiotics, and phytohemagglutinin. Colcemid was added before harvest; cells were treated with 0.075 mol/L KCl and fixed in methanol:acetic acid (3:1). GTG-banded metaphases were evaluated at approximately 450–550-band resolution. At least 30 metaphases were analyzed using an Olympus BX-63 microscope with ASI software (version 8.3.2). Karyotype nomenclature followed ISCN 2024 [10]. A structurally abnormal chromosome 11 containing additional banded material within the long arm was consistently identified. The banding pattern was interpreted as 46,XY,dup(11)(q21q23) (Figure 1), indicating an interstitial duplication of 11q21–q23 and partial trisomy for the duplicated segment. No additional numerical or structural abnormality was detected at the resolution of conventional karyotyping. Figure 1: Conventional GTG-banded cytogenetic findings. (A) Representative metaphase showing the structurally abnormal chromosome 11 (red arrow). (B) Karyogram demonstrating one abnormal chromosome 11 with duplicated material in the long arm (red arrow), interpreted as 46,XY,dup(11)(q21q23).

The phenotype in our case overlaps with recurrent manifestations reported across the partial 11q trisomy spectrum, including prenatal and postnatal growth impairment, hypotonia, developmental delay, dysmorphic facial features, small extremities, and congenital heart disease [1, 2, 4]. The short nose, long philtrum, microretrognathia, hypertelorism/epicanthi, and low-set posteriorly rotated ears also resemble features described in earlier reports [1, 2, 4]. However, many historically reported patients had terminal duplications extending to qter and, in some families, an additional chromosomal imbalance resulting from translocation segregation. Direct genotype-phenotype extrapolation from those cases to an interstitial q21–q23 duplication is therefore inappropriate. A useful comparator is the molecularly characterized case reported by Chen et al., in which a de novo 9.04-Mb duplication of 11q22.3–q23.3 was demonstrated. At 10 months, that child was small for age and had abnormal psychomotor development, facial dysmorphism, and small hands and feet [8]. The clinical overlap with our case supports the relevance of copy-number gain in this region, but equivalence cannot be assumed because our case is defined only at chromosome-band level. Variable expressivity is a prominent feature of reported interstitial 11q duplications. Yelavarthi and Zunich described a familial 11q13.5–q21 duplication in a child with developmental delay and a more mildly affected mother, whereas Zarate et al. reported a de novo interstitial 11q duplication in an individual with mild dysmorphism but normal development and intelligence [5, 6]. These observations support interval-specific and family-specific counseling rather than a single prognosis for all 11q duplications. Molecular characterization of distal 11q gains has additionally shown that apparently similar band-level abnormalities may represent different copy-number architectures [7, 9]. The feeding-associated respiratory symptoms warrant cautious interpretation. Zhao et al. reported upper airway obstruction caused by epiglottic malformation in three of four patients with partial 11q trisomy and proposed an 11q21–q23.2 critical region for that finding [4]. In our case, only mild oropharyngeal incoordination was documented; a structural airway abnormality was not demonstrated. The small muscular ventricular septal defect is compatible with the broader reported spectrum of congenital heart defects in partial 11q duplication [1, 4]. Management should be phenotype-directed. Developmental surveillance and early physiotherapy are appropriate for hypotonia and motor delay. Growth and head circumference should be followed serially, and persistent feeding-associated respiratory symptoms should prompt reassessment for aspiration or airway dysfunction. The ventricular septal defect requires routine pediatric cardiology follow-up. Additional investigations should be guided by evolving clinical findings rather than by assuming that complications reported in larger or terminal 11q duplications will occur in this child. Genetic counseling should clearly separate established findings from unresolved questions. The karyotype provides a plausible unifying explanation for the infant's growth, neurodevelopmental, dysmorphic, limb, and cardiac abnormalities, but it does not define the exact duplicated sequence. If available, chromosomal microarray would refine the interval and improve copy-number interpretation [11, 12]. Parental karyotyping is central to recurrence-risk assessment. If one parent carries the same visible duplication, counseling should emphasize the variable expressivity documented for interstitial 11q gains [5, 6]. If a parent carries a balanced translocation, inversion, or insertion involving the duplicated segment, recurrence risk may be substantially higher and must be estimated from the specific rearrangement. If both parental karyotypes are normal, a de novo event is favored and recurrence is generally low but not zero because germline mosaicism cannot be completely excluded [13]. For future pregnancies, diagnostic testing by chorionic villus sampling or amniocentesis can be tailored to the familial rearrangement once its mechanism is defined. When a parental structural rearrangement is identified and assisted reproduction is being considered, preimplantation genetic testing for structural rearrangements (PGT-SR) may be an option in appropriately resourced settings [14]. Limitations: The main limitations are the absence of higher-resolution genomic characterization and parental studies. Chromosomal microarray would refine the duplicated interval and define its genomic boundaries more precisely [11, 12].

This case demonstrates that conventional GTG-banded karyotyping can provide a definitive cytogenetic diagnosis when a constitutional duplication is large enough to be resolved at chromosome-band level. In addition to identifying the involved chromosome and duplicated region, karyotyping provides a genome-wide assessment for accompanying numerical or structural abnormalities and forms an important basis for parental studies and recurrence-risk counseling. Higher-resolution genomic testing can subsequently refine the duplicated interval when clinically indicated.

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