|Year : 2022 | Volume
| Issue : 2 | Page : 136-138
A case of 7q21.3q31.1 deletion in a preterm boy with feeding intolerance and cyanotic episodes
Anwar K Jones
Department of Neonatology, Children's Mercy Hospital, Wichita, Kansas, USA
|Date of Submission||02-Oct-2021|
|Date of Decision||11-Nov-2021|
|Date of Acceptance||17-Jan-2022|
|Date of Web Publication||20-Apr-2022|
Anwar K Jones
Department of Neonatology, Children's Mercy Hospital, St. Joseph Campus, Wichita, Kansas
Source of Support: None, Conflict of Interest: None
This report describes a preterm male infant with phenotypic features of mild facial dysmorphism, congenital abnormalities of the hands and feet, corneal clouding, hypertonia, bilateral sensorineural hearing loss, and bilateral ventriculomegaly. His clinical course was significant for severe cyanotic episodes associated with the advancement of feed volume. Microarray analysis identified a large constitutional de novo deletion of 7q21.3q31.1. This rare deletion has never been reported in a preterm infant, and the management of this patient will help offer clinical guidance for this genetic condition.
Keywords: 7q21.3q31.1, ectrodactyly, intermediate 7q deletion, interstitial 7q deletion
|How to cite this article:|
Jones AK. A case of 7q21.3q31.1 deletion in a preterm boy with feeding intolerance and cyanotic episodes. J Clin Neonatol 2022;11:136-8
| Introduction|| |
Interstitial 7q chromosome deletion is a rare chromosome disorder involving a large area of the cytogenetic bands. At the time of this report, only four reported cases specifically involved intermediate 7q21.3q31 deletion; and this is the only case that involves a premature infant. Patients with intermediate (7q21-q32) deletions of this chromosome have varying phenotypic expressions. Consistently reported features include developmental delay, growth and psychomotor retardation, hypotonia, feeding problems, unusual cry, microcephaly, brain atrophy, seizures, eye anomalies (most commonly, upslanted palpebral fissures, hypertelorism, and glaucoma), low-set dysmorphic ears, flat nasal bridge, largemouth with downturned corners, thin upper lip and anomalous philtrum length, micrognathia, palatal and cardiac defects, hand/foot malformations (ectrodactyly), single palmar creases, genital malformation, and recurrent infections. We report a male infant with chromosome 7q21.3q31.1 deletion. Outstanding features in this infant were mild dysmorphic features, ocular abnormality, feeding problems associated with significant respiratory compromise, hearing loss, and hand and foot abnormalities.
| Case Report|| |
This male infant was born to an 18-year-old African American woman. Mild bilateral ventriculomegaly and mild polyhydramnios were noted on a second-trimester ultrasound. He was delivered at 29 weeks, was appropriate for gestational age, and required noninvasive mechanical ventilation in the neonatal intensive care unit (NICU). On admission, phenotypic features included short forehead, widened anterior fontanelle, corneal clouding, low-set posteriorly rotated ears, fifth finger clinodactyly, right-sided single palmar crease, bilateral partial syndactyly of the fourth and fifth metatarsals, broad-based feet, and hypertonia. Chromosomal microarray analysis was performed using both copy number and single-nucleotide polymorphism probes on a whole-genome array (Affymetrix CytoScan HD platform). An interstitial intermediate Pathogenic deletion at 7q21.3q31.1 10.6 Mb arr (hg19) 7q21.3q31.1 (97,257,697-107,830,464) ×1 was reported. A 10.6 megabase deletion was observed involving 201 known genes. Routine head ultrasound on the day of life 7 confirmed ventriculomegaly with Grade III intraventricular hemorrhage. His NICU stay was complicated by episodes of significant respiratory compromise whenever his feed volume approached 100 mL/kg/day. This compromise persisted regardless of the type of respiratory support (endotracheal intubation or noninvasive) and was exhibited by severe bradycardia, apnea, and cyanosis requiring positive pressure ventilation. After each episode, the infant continued to have clusters of significant bradycardia spells, prompting cessation of feeds. Feeds were usually resumed at a lower volume after 24 h. By 1 month of age, the infant was transferred to a Level IV NICU for further management of his cyanotic spells. An echocardiogram (ECHO) revealed normal heart function, a small patent ductus arteriosus, and mild hypoplastic pulmonary arteries. Renal ultrasound revealed normal anatomy. Brain magnetic resonance imaging (MRI) showed normal parenchymal signal and morphology, mild prominence of the lateral and third ventricles, and the supratentorial extra-axial space. An electroencephalogram (EEG) disclosed no epileptiform activity. He was tried on continuous and transpyloric feeds multiple times. A gastrostomy tube (G-tube) was placed at 44-week postconceptional age (PCA) along with a Nissen fundoplication and bilateral hernia repair. He continued to exhibit poor suck-swallow coordination, hypertonicity, and full back arching when fed orally. Ophthalmology exam showed mildly elevated ocular pressure. He was discharged home at 46-week PCA on G-tube feeds and EleCare 26 kcal/oz. Home respiratory support included low-flow nasal cannula. Clonazepam was prescribed for his dystonia. Audiology follow-up for his bilateral sensorineural deficits was arranged along with follow-up with neurology, development clinic, and genetics.
| Discussion|| |
Interstitial 7q deletions are rare and usually occur de novo. Because these interstitial deletions can involve up to 1,150 genes occurring in three different cytogenetic bands, their phenotypic differences can be heterogeneous, making it difficult to describe a specific syndrome.,
GJC3 is a candidate gene that may have contributed to this patient's bilateral sensorineural hearing loss. SLC26A4 belongs to the same gene family, and mutations in an anion transport protein are known to cause nonsyndromic hearing loss with enlarged vestibular aqueduct.,
Phenotypic features (some of which are seen in this patient) of growth retardation, microcephaly, flat facial profile, downturned corners of the mouth, low-set simple ears, upturned nose, ocular anomalies, global developmental delay, and dilation of the cerebral ventricles have been described in mutations of PLOD3, a gene encoding a collagen-modifying enzyme.,
Many patients with deletions in the region of AP4M1 have been reported with either hypotonia, hypertonia, or both, that may help explain the progressive hypertonia and spasticity seen in this case.
Some degree of SHFM1, DLX5, or DLX6 deletions may be the cause for this patient's mild ectrodactyly. SHFM1 may also be associated with his clinodactyly.,,
There is a paucity of guidance in the literature for these cases. Our approach for these patients involves management by a multidisciplinary team in a higher-level NICU. Screening ECHO and renal ultrasound should be attained to rule out structural abnormalities.
These infants with reflux and extreme feeding difficulties should be considered for early G-tube placement and Nissen fundoplication to ensure optimal nutrition, growth, and development. Beyond the newborn period, feeding histories on 14 children with 7q deletion show additional challenges such as food intolerance, difficulty and persistent reluctance to chew, a preference for semisolid foods such as yogurt, and a tendency to stuff the mouth. Families also report a reluctance to take lumpy food and a narrow range of tastes and textures.
Although our patient did not develop seizures, he did have brain abnormalities and developmental delays similar to the patients with mutations of the KPNA7 gene. It would be appropriate for such infants to undergo noncontrast brain MRI. Because of the possibility of clinical and subclinical seizures, an EEG, if warranted, should be considered early in the infant's clinical course.
Due to their abnormal muscle tone, these infants may benefit from early occupational therapy and medications such as clonazepam. Children may later require long-term support with sitting and walking and wheelchair assistance. Most individuals with this deletion will show some level of developmental delay and will therefore benefit from extra support for cognitive disability. Case studies suggest that the closer the deletion is to 7q21, the more support the child may require. Finally, parental FISH studies are recommended to identify balanced rearrangement and risk of recurrence.
I would like to acknowledge the Medical Writing Center at Children's Mercy Hospital for editing this manuscript.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Katz OL, Krantz ID, Noon SE. Interstitial deletion of 7q22.1q31.1 in a boy with structural brain abnormality, cardiac defect, developmental delay, and dysmorphic features. Am J Med Genet C Semin Med Genet 2016;172:92-101.
Martínez-Jacobo L, Córdova-Fletes C, Ortiz-López R, Rivas F, Saucedo-Carrasco C, Rojas-Martínez A. Delineation of a de novo 7q21.3q31.1 deletion by CGH-SNP arrays in a girl with multiple congenital anomalies including severe glaucoma. Mol Syndromol 2013;4:285-91.
Rare Chromosome Disorder Support Group. 7q Deletions between 7q21 and 7q32. Understanding Chromosome Disorders. Unique; 2011. Available from: https://www.rarechromo.org
.[Last accessed on 2021 Nov 11].
Everett LA, Belyantseva IA, Noben-Trauth K, Cantos R, Chen A, Thakkar SI, et al.
Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome. Hum Mol Genet 2001;10:153-61.
Salo AM, Cox H, Farndon P, Moss C, Grindulis H, Risteli M, et al.
A connective tissue disorder caused by mutations of the lysyl hydroxylase 3 gene. Am J Hum Genet 2008;83:495-503.
Scherer SW, Poorkaj P, Allen T, Kim J, Geshuri D, Nunes M, et al.
Fine mapping of the autosomal dominant split hand/split foot locus on chromosome 7, band q21.3-q22.1. Am J Hum Genet 1994;55:12-20.
Paciorkowski AR, Weisenberg J, Kelley JB, Spencer A, Tuttle E, Ghoneim D, et al.
Autosomal recessive mutations in nuclear transport factor KPNA7 are associated with infantile spasms and cerebellar malformation. Eur J Hum Genet 2014;22:587-93.