Feeding dysfunction in a neonate with interstitial deletion of chromosome 2q24.3-q32.1: a case report

Abstract

Background

Neonates with multiple congenital anomalies present diagnostic and management challenges, especially when accompanied by multisystemic alterations and feeding difficulties. Chromosomal microarray analysis enables identification of pathogenic variants that explain complex clinical features and guide individualized management.

Case presentation

We report a Hispanic female neonate born at 37 weeks with intrauterine growth restriction. Clinical features included micrognathia, microphthalmia, high-arched palate, low-set posteriorly rotated ears, bilateral plantar syndactyly, shoulder girdle malformations, generalized hypotonia, and absent suck reflex. Neuroimaging revealed ventriculomegaly, suspected cerebellar hypoplasia, and occipital horn blood products. Chromosomal microarray identified a 15.72 Mb deletion at 2q24.3-q32.1 encompassing SCN1A, SCN2A, SCN3A, and the HOXD cluster, classified as pathogenic. The infant demonstrated profound oral-motor dysfunction with absent suck and impaired suck-swallow-breathe coordination. Videofluoroscopic swallow study was not performed due to clinical instability; bedside assessments revealed no desaturation, bradycardia, or aspiration during monitored feeding trials. Stridor and tracheal tugging raised suspicion for laryngomalacia. Intensive multidisciplinary feeding therapy including speech-language pathology, oral-motor stimulation with lemon swabs, and positioning strategies led to progressive improvement. By day 25, the infant transferred 60 mL orally with slow-flow nipple. By discharge on day 38, full oral feeding was achieved (60 mL Enfamil every 3 h with good sucking technique), with successful breastfeeding attempts initiated. Discharge weight was 2.415 kg (290-gram gain from birth, averaging 7.6 g/day). Nasogastric supplementation was discontinued and gastrostomy tube placement successfully deferred.

Conclusion

This case demonstrates the phenotypic spectrum of 2q24.3-q32.1 deletions with detailed documentation of severe feeding dysfunction requiring 38-day hospitalization. While SCN gene haploinsufficiency may contribute to feeding impairment through effects on brainstem motor coordination, the etiology is likely multifactorial, involving hypotonia, craniofacial anomalies, and airway abnormalities. Early recognition of feeding dysfunction and intensive multidisciplinary intervention resulted in successful achievement of full oral feeding. This underscores the value of chromosomal microarray testing and comprehensive follow-up for developmental monitoring and seizure surveillance.

Background

Interstitial deletions of chromosome 2q24.3-q32.1 are exceedingly uncommon, with fewer than 20 cases documented in the literature [1–4]. The phenotypic spectrum varies depending on the specific genomic coordinates and size of the deletion. Reported manifestations include intrauterine and postnatal growth restriction, craniofacial dysmorphisms (micrognathia, cleft palate, ear anomalies), limb malformations (syndactyly, digital anomalies), seizures, developmental delay, hypotonia, and congenital heart defects [1–5]. These features reflect disruption of critical genes within this region, including the neuronal sodium channel genes SCN1A, SCN2A, and SCN3A, the neurodevelopmental gene TBR1, and the HOXD cluster essential for skeletal patterning [5].

Chromosomal microarray analysis has become a first-line diagnostic tool for neonates with multiple congenital anomalies, enabling detection of submicroscopic copy number variants and refining genotype-phenotype correlations [6]. This case report describes a neonate with an interstitial deletion of 2q24.3-q32.1 who presented with features consistent with previously reported deletions in this region, including significant feeding difficulties requiring intensive multidisciplinary therapy. We provide detailed clinical and feeding data, compare this case with prior reports, and discuss potential mechanisms underlying the observed phenotype.

Case presentation

A Hispanic female neonate was born at an estimated gestational age of 37 weeks via vaginal delivery to a 38-year-old gravida 2 para 1 mother. Pregnancy was notable for placental insufficiency with estimated fetal weight below the 1st percentile. Maternal history included advanced maternal age, prior cesarean delivery, and prenatal Streptococcus agalactiae colonization treated with intrapartum antibiotics. The mother had no chronic medical conditions, took aspirin and prenatal vitamins, and reported no known drug allergies.

At delivery, Apgar scores were 6 and 7 at 1 and 5 min, respectively. Birth weight was 2.125 kg (below 3rd percentile), length 43 cm (5th percentile), and head circumference 31 cm (5th percentile), consistent with intrauterine growth restriction. Initial vital signs included blood pressure 65/33 mmHg, heart rate 142 bpm, respiratory rate 48 breaths per minute, oxygen saturation 98%, and temperature 35.4 °C.

The infant was admitted to the neonatal intensive care unit for respiratory distress and feeding difficulties. Physical examination revealed a small-for-gestational-age infant with grunting respirations, weak cry, and poor secretion clearance. Craniofacial examination demonstrated microphthalmia, micrognathia, high-arched palate, and low-set posteriorly rotated ears (Fig. 1). Limb findings included bilateral plantar syndactyly of the 2nd through 5th toes (Fig. 2), clinodactyly of bilateral hands, and shoulder girdle malformations. A sacral tuft of hair was present. Neurological evaluation revealed generalized hypotonia, absent suck reflex, and phasic bite movements.

Fig. 1.

Clinical photograph showing characteristic dysmorphic features. Photograph demonstrates low-set, posteriorly rotated ears and micrognathia (small mandible), consistent with the phenotypic spectrum of 2q24.3-q32.1 deletions. Patient shown during neonatal intensive care hospitalization with cardiac monitoring leads in place. Wrist identifier obscured to protect patient privacy

Fig. 2.

Plantar syndactyly. Photograph showing plantar syndactyly of the 2nd through 5th toes, a characteristic limb anomaly associated with 2q24.3-q32.1 deletions. Syndactyly was present bilaterally on clinical examination

Infectious and metabolic workup to exclude congenital infections was negative, prompting further assessment with imaging and genetic testing. Brain magnetic resonance imaging (MRI) on day 5 of life confirmed mild ventriculomegaly, suspected cerebellar hypoplasia, and small occipital horn blood products (Fig. 3). Additional multisystemic diagnostic evaluations and their findings are summarized in Table 1.

Fig. 3.

Patient Axial T2-weighted MRI. Axial T2-weighted MRI images of the posterior fossa demonstrating bilateral cerebellar hypoplasia with preserved cerebellar architecture

Table 1.

Summary of additional diagnostic evaluations in patient. Comprehensive summary of diagnostic studies performed during the 38-day neonatal intensive care hospitalization, including imaging modalities, laboratory investigations, and subspecialty consultations. All studies were performed at the same hospital between the patient’s date of birth to 38 days

System	Findings
Head Ultrasound	● Asymmetric ventricular dilatations with septations
Brain MRI	● Ventriculomegaly ● Cerebellar hypoplasia ● Small occipital horn blood products
Echocardiogram	● Patent foramen ovale (PFO) ● Patent ductus arteriosus (PDA) ● Ventricular septal defects (VSD)
Abdominal Ultrasound	● Hydronephrosis and right hepatic lobe hematoma
Ophthalmologic exam (RetCam)	● Roth spots ● Vitreous hemorrhage ● Regressing stage 2 retinopathy of prematurity
CBC with peripheral smear	● Mild thrombocytopenia ● Elevated RDW ● Nucleated RBCs ● Target cells, ovalocytes, and teardrops
Newborn Hearing Screen	● Passed

Feeding Assessment and Management: The infant’s feeding course was characterized by profound oral-motor dysfunction with absent suck reflex and ineffective coordination of the suck-swallow-breathe sequence. Initial oral feeding attempts were unsuccessful, requiring nasogastric tube supplementation for all nutritional needs beginning on day 1. During early feeding evaluations, the infant exhibited a weak cry and intermittent stridor with tracheal tugging, raising clinical suspicion for laryngomalacia. Formal otolaryngology consultation was recommended for outpatient follow-up to confirm the diagnosis and assess severity. Videofluoroscopic swallow study (VFSS) was not performed due to the infant’s clinical instability during the first weeks of life and her young age. Throughout the hospitalization, bedside swallow safety assessments by speech-language pathology revealed no episodes of oxygen desaturation, bradycardia, persistent coughing, or clinical signs suggestive of aspiration during carefully monitored feeding attempts. The infant was able to manage saliva appropriately, and swallowing skills were observed to be intact.

A structured, intensive feeding therapy program was implemented by speech-language pathology. Initial assessments on day 12 revealed delayed oral response to oral reflexes, inability to exhibit sucking response, active phasic bite indicative of possible neurological deficiency, and inability to coordinate the suck-swallow-breathe pattern. Interventions included oral-motor stimulation with lemon swabs, non-nutritive sucking exercises with a pacifier, caregiver education, slow-flow nipple trials, elevated side-lying positioning to reduce airway compromise and improve bolus control, careful pacing techniques, and brief cue-based feeding sessions limited to 20 min to minimize fatigue and avoid aspiration risk. Parents were extensively counseled about feeding strategies, positioning, and the need for patience during the maturation process.

Over the subsequent two weeks, gradual improvement was observed. By day 17, the infant began responding to sensory stimuli with lemon swabs and demonstrated functional non-nutritive sucking movements. A significant breakthrough occurred on day 25 when the infant successfully transferred 60 mL orally using a slow-flow nipple in an elevated side-lying position with stable respiratory rate and oxygen saturation throughout. At this assessment, phasic bite was no longer present, oral-motor response for milk transfer was present for both bottle and breastfeeding approaches, and the infant demonstrated ability to coordinate suck-swallow-breathe pattern, latch effectively, and transfer milk from the nipple.

By day 26, the infant was receiving 50–60 mL per feed via nasogastric tube, providing approximately 120 cal/kg/day (total daily intake approximately 178 mL/kg/day at weight of 2.3 kg). At day 30, oral feeding skills had progressed to allow approximately 20 mL per feed orally, with the remainder provided via nasogastric supplementation. A multidisciplinary team meeting on day 19 had considered gastrostomy tube placement; however, given the trajectory of improvement with intensive therapy, parents elected to defer this procedure and continue working on feeding skills. Gastrostomy equipment was available in the unit but ultimately was not utilized.

Over the subsequent eight days, continued intensive feeding therapy resulted in further substantial improvement. By day 38 of life, the infant demonstrated consistent ability to take 60 mL per feed orally with good sucking technique, stable respiratory pattern, and no signs of aspiration or distress. The mother successfully initiated breastfeeding attempts before offering supplemental bottle feeds. Weight progression remained steady, reaching 2.415 kg at discharge (weight gain of 85 g from day 30 to day 38, averaging 10.6 g/day during the final week). Given the achievement of full oral feeding without need for nasogastric supplementation, gastrostomy tube placement was successfully deferred.

Growth and Nutrition: Weight progression showed gradual gain from birth weight of 2.125 kg to 2.30 kg by day 26, 2.33 kg by day 30, and 2.415 kg at discharge on day 38, representing average weight gain of 7.6 g/day over the hospitalization period. The infant demonstrated adequate voiding and stooling patterns throughout hospitalization.

Genetic Testing: Chromosomal microarray analysis revealed a 15.72 Mb interstitial deletion at 2q24.3-q32.1 (arr[hg19] 2q24.3q32.1(167,361,613 − 183,085,109)x1) spanning multiple OMIM genes, including XIRP2, PDE1A, SCN1A, SCN2A, SCN3A, and the HOXD cluster (Fig. 4). This CNV was classified as pathogenic according to ACMG/ClinGen CNV interpretation guidelines, based on its large size, inclusion of multiple dosage-sensitive genes (including SCN1A, SCN2A, and SCN3A), and overlap with previously reported pathogenic deletions in this region. No additional pathogenic or likely pathogenic copy number variants were detected. Parental FISH testing was recommended to confirm de novo status.

Fig. 4.

Chromosomal microarray visualization of the 2q24.3-q32.1 deletion. A Ideogram showing the location of the pathogenic deletion (red bar) on chromosome 2 at bands q24.3-q32.1. B Detailed genome browser view (UCSC Genome Browser, GRCh37/hg19) [7] illustrating the 15.72 Mb interstitial deletion encompassing chromosome bands 2q24.3 through 2q32.1 (arr[hg19] 2q24.3q32.1(167,361,613-183,085,109)x1). The deleted region contains multiple OMIM genes including SCN1A, SCN2A, SCN3A, and the HOXD cluster, which are critical for neurological function and skeletal patterning. Chromosome bands are shown with FISH mapping clone positions

Hospital Course and Discharge: The infant remained in the neonatal intensive care unit due to feeding challenges and need for close monitoring. Respiratory support was discontinued by day 2, and the infant remained stable on room air thereafter. Cardiac evaluation revealed small patent foramen ovale, small patent ductus arteriosus, and muscular ventricular septal defect, none requiring intervention. Neurology was consulted due to hypotonia, abnormal neuroimaging, and seizure risk associated with SCN gene haploinsufficiency; electroencephalogram was scheduled for outpatient follow-up. The infant was discharged home on day 38 of life on full oral feeds (60 mL Enfamil 20 cal/oz every 3 h) with continued breastfeeding attempts, at a weight of 2.415 kg. Comprehensive multidisciplinary outpatient follow-up was arranged including genetics, neurology, developmental pediatrics, feeding therapy (speech-language pathology, occupational therapy, physical therapy), cardiology, and otolaryngology for formal laryngeal assessment, with close parental support and education provided throughout the hospitalization.

Discussion

The clinical presentation of this patient reflects the phenotypic variability associated with 2q24.3-q32.1 deletions, as documented in prior case reports (Table 2). Our patient exhibited many features previously described in the literature, including intrauterine and postnatal growth restriction, craniofacial dysmorphisms, limb anomalies (particularly digital malformations), neurological abnormalities (hypotonia, brain malformations), and cardiac defects [1–5]. Feeding difficulties associated with hypotonia have been noted in earlier reports, particularly in infants with significant central nervous system involvement [3, 5]. Our case provides detailed quantitative documentation of severe early feeding dysfunction, its clinical trajectory over a 38-day hospitalization, specific therapeutic interventions employed, and gradual response to intensive multidisciplinary therapy culminating in successful achievement of full oral feeding at discharge.

Table 2.

Comparison of our case with previously reported 2q24.3-q32.1 deletions. Clinical features of the proband compared with four previously published cases of interstitial 2q24.3-q32.1 deletions. +: feature present; NR: not reported in the literature. Hospital course, feeding difficulties, and growth restriction are consistently reported across cases, while feeding dysfunction has been documented in varying levels of detail in the literature. Our case provides the most comprehensive quantitative documentation of feeding progression and therapeutic interventions to date

Feature	Our Case	Boles 19952	Pescucci 20073	Zhu 20221
Deletion size	15.7 Mb	~ 12 Mb	~ 18 Mb	~ 13.8 Mb
Growth restriction	+	+	+	+
Craniofacial dysmorphism	+	+	+	+
Limb anomalies	+ (syndactyly)	+ (digital)	+ (digital)	+ (syndactyly)
Hypotonia	+	NR	+	NR
Feeding difficulties	+ (detailed)	NR	+ (brief mention)	NR
CNS anomalies	+	NR	+	+
Cardiac defects	+	+	+	+

+: present, NR: Not reported

The successful implementation of intensive, protocolized feeding therapy resulted in clinically meaningful functional improvement, culminating in achievement of full oral feeding by discharge. The trajectory from complete nasogastric dependence on day 1, through the critical breakthrough at day 25 when 60 mL oral transfer was first achieved, to consistent oral feeding with good technique by day 38 demonstrates the potential for substantial gains with persistent, multidisciplinary intervention. The ability to defer gastrostomy tube placement represents an important outcome, as it avoids the risks, costs, and psychosocial impacts associated with invasive nutritional support. Early identification of feeding dysfunction as a core manifestation of 2q24.3-q32.1 deletions, proactive initiation of speech-language pathology services, intensive oral-motor stimulation protocols, positioning strategies, and extensive caregiver education and support were key factors enabling this successful outcome.

The 2q24.3-q32.1 region contains several genes critical for neurological development and function. The SCN1A, SCN2A, and SCN3A genes encode voltage-gated sodium channel alpha subunits essential for neuronal excitability [5, 8, 9]. Haploinsufficiency of these genes has been strongly associated with epilepsy phenotypes, including Dravet syndrome and other early-onset epileptic encephalopathies [10]. Sodium channel genes are also expressed in brainstem motor nuclei involved in coordinating complex motor behaviors such as sucking, swallowing, and breathing [9]. Given this expression pattern, SCN gene haploinsufficiency may contribute to the observed feeding dysfunction by impairing the neural circuits responsible for suck-swallow-breathe coordination.

However, it is important to recognize that multiple factors likely contributed to this infant’s feeding difficulties, and attributing the dysfunction solely to SCN haploinsufficiency would be overly simplistic. Generalized hypotonia, a well-recognized feature of 2q24.3-q32.1 deletions [3, 5], impairs the muscle strength and coordination necessary for effective feeding. Structural craniofacial anomalies, including micrognathia and high-arched palate, can mechanically interfere with latch and bolus formation. Additionally, the clinical findings of stridor and tracheal tugging suggestive of laryngomalacia, while not formally confirmed by otolaryngology during hospitalization, may have contributed to respiratory compromise and fatigue during feeding attempts. The combination of early term birth (37 weeks gestational age) and severe intrauterine growth restriction may have also delayed the maturation of feeding reflexes and overall neurodevelopmental readiness for coordinated oral feeding. Therefore, while SCN haploinsufficiency represents a plausible contributory mechanism worthy of further investigation, feeding dysfunction in this population is likely multifactorial in etiology.

This case reinforces the importance of chromosomal microarray analysis as a first-tier diagnostic test for neonates with multiple congenital anomalies [6]. Early genetic diagnosis enables anticipatory guidance regarding potential complications, facilitates coordinated subspecialty care, and provides families with prognostic information and recurrence risk counseling. For infants with 2q24.3-q32.1 deletions, multidisciplinary follow-up should include genetics, neurology (for seizure monitoring and neurodevelopmental assessment), feeding therapy, cardiology, ophthalmology, otolaryngology, and developmental pediatrics.

Limitations: This report has several limitations. Videofluoroscopic swallow study was not performed, limiting our ability to definitively assess swallow mechanics and aspiration risk, though bedside clinical assessments by experienced speech-language pathologists suggested intact swallowing with no clinical signs of aspiration. Formal otolaryngology evaluation was not completed during hospitalization, and laryngomalacia remains a clinical suspicion pending outpatient specialty assessment. Parental FISH testing was recommended but confirmation of de novo status was not documented at the time of discharge. Follow-up data beyond the neonatal period are not yet available in this report, precluding assessment of long-term feeding outcomes, neurodevelopment, and seizure occurrence. Additionally, as a single case report, generalizations regarding feeding outcomes in all patients with similar deletions cannot be made.

Conclusion

This case report documents the clinical phenotype and early feeding course of a neonate with a 2q24.3-q32.1 deletion over a 38-day hospitalization. The patient’s presentation was consistent with previously described cases involving growth restriction, craniofacial dysmorphisms, limb malformations, neurological abnormalities, and cardiac defects. Severe early feeding dysfunction was a prominent feature requiring intensive, prolonged multidisciplinary intervention, with successful achievement of full oral feeding by discharge. The etiology of feeding dysfunction in this population is likely multifactorial, with potential contributions from SCN gene haploinsufficiency affecting brainstem motor coordination, generalized hypotonia, structural craniofacial anomalies, airway issues, and developmental immaturity. Intensive speech-language pathology interventions, including oral-motor stimulation, positioning strategies, and caregiver education, resulted in meaningful functional improvement and successful deferral of gastrostomy tube placement. Chromosomal microarray analysis remains essential for diagnosing complex congenital anomaly syndromes, and early genetic diagnosis facilitates coordinated, anticipatory care. Clinicians caring for infants with 2q24.3-q32.1 deletions should be alert to feeding dysfunction as part of the phenotypic spectrum and consider early, aggressive, multidisciplinary feeding interventions to optimize nutritional and developmental outcomes.

Authors’ contributions

NAR drafted the manuscript, conducted the literature review, and coordinated clinical data collection. JMRR, ERP, AMG, AC, and SJB contributed to data acquisition, literature review, table preparation, and manuscript editing. APV supervised the clinical interpretation, verified the diagnostic findings, and critically revised the manuscript. All authors critically reviewed the report, commented on drafts of the manuscript, and approved the final version.

Funding

No specific funding was received for this work.

Data availability

All data generated or analyzed during this study are included in this published article. Additional figures (clinical photographs, FISH documentation, and chromosomal microarray ideogram) will be provided upon journal request and with maintained parental consent.

Declarations

Ethics approval and consent to participate

Ethics approval was not required for this case report according to institutional guidelines. Written informed consent for participation and publication was obtained from the patient’s parents.

Consent for publication

Written informed consent for publication and any accompanying images was obtained from the patient’s parents.

Competing interests

The authors declare no competing interests.