Sivakumaran TA, Grebe TA. 15q26.3 deletions distal to IGF1R cause growth retardation, congenital heart defect and skeletal anomalies: Case report and review of literature. Am J Med Genet A. 2023 Sep;191(9):2392-2397. doi: 10.1002/ajmg.a.63350. Epub 2023 Jul 12. PMID: 37434556.
Abstract
15q26 deletion is a rare genomic disorder characterized by intrauterine and postnatal growth retardation, microcephaly, intellectual disability, and congenital malformations. Here, we report a 4-month-old female with intrauterine growth retardation, short stature, pulmonary hypertension, atrial septal defect and congenital bowing of long bones of the legs. Chromosomal microarray analysis showed a de novo deletion of approximately 2.1 Mb at 15q26.3 region that does not include IGF1R. Our analysis of patients documented in the literature and the DECIPHER database with 15q26 deletions distal to IGF1R, including 10 patients with de novo pure deletions, allowed us to define the smallest region of overlap to 686 kb. This region includes ALDH1A3, LRRK1, CHSY1, SELENOS, SNRPA1, and PCSK6. We propose haploinsufficiency of one or more genes, besides IGF1R, within this region may contribute to the clinical findings in patients with 15q26.3 deletion.
Dincer BT, Ozdemir EM, Cetincelik U, Ucar A. Drayer Syndrome due to Chromosome 15q26.3 Deletion: Response to Growth Hormone Treatment. Sisli Etfal Hastan Tip Bul. 2024 Dec 24;58(4):521-523. doi: 10.14744/SEMB.2024.01879. PMID: 39816431; PMCID: PMC11729826.
Abstract
Chromosome 15q26 deletion is a rare condition that causes short stature and is associated with intrauterine growth restriction (IUGR), failure to thrive, congenital heart disease and many congenital malformations. The insulin growth factor receptor (IGF-1R) on chromosome 15 has many important roles, especially in growth regulation. Our case is an 18-month-old small for gestational age girl who presented with severe short stature, microcephaly and minor dysmorphic features. Chromosome microarray revealed 15q26 deletion including the IGF1R gene. Recombinant growth hormone (rGH) has been used in patients with IGF-1R defects with variable treatment responses. The reason for rGH unresponsiveness in some patients with terminal chromosome 15q deletion is still unclear. Herein we discuss the use of rGH in a patient with heterozygous IGF1R deletion and emphasize the need for further follow-up regarding other endocrine disorders.
Benbouchta Y, De Leeuw N, Amasdl S, Sbiti A, Smeets D, Sadki K, Sefiani A. 15q26 deletion in a patient with congenital heart defect, growth restriction and intellectual disability: case report and literature review. Ital J Pediatr. 2021 Sep 16;47(1):188. doi: 10.1186/s13052-021-01121-5. PMID: 34530895; PMCID: PMC8447573.
Abstract
Background: 15q26 deletion is a relatively rare chromosomal disorder, and it is described only in few cases. Patients with this aberration show many signs and symptoms, particularly pre- and postnatal growth restriction, developmental delay, microcephaly, intellectual disability and various congenital malformations.
Case presentation: We report on a girl, 4 years old, of consanguineous parents, with a 15q26 deletion. Clinical manifestations included failure to thrive, developmental delay, microcephaly, dysmorphic facies with broad forehead, hypertelorism, narrowed eyelid slits and protruding columella. The patient also showed skeletal abnormalities, especially clinodactyly of the 5th finger, varus equine right foot and left club foot. Additionally, she had teething delay and divergent strabismus. Heart ultrasound displayed two atrial septal defects with left-to-right shunt, enlarging the right cavities. Routine cytogenetic analysis revealed a shortened 15q chromosome. Subsequent array analysis disclosed a terminal 9.15 Mb deletion at subband 15q26.1-q26.3. Four candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, CHD2 and MEF2A.
Poot M, Verrijn Stuart AA, van Daalen E, van Iperen A, van Binsbergen E, Hochstenbach R. Variable behavioural phenotypes of patients with monosomies of 15q26 and a review of 16 cases. Eur J Med Genet. 2013 Jul;56(7):346-50. doi: 10.1016/j.ejmg.2013.04.001. Epub 2013 Apr 16. PMID: 23603061.
Abstract
Patients with trisomy or tetrasomy of distal 15q show a recognizable overgrowth syndrome, whereas patients with a monosomy of 15q26 share some degree of pre- and postnatal growth retardation, but differ with respect to facial and skeletal dysmorphisms, congenital heart disease and intellectual development. By reviewing 16 cases with losses of 15q26 we found that the size of the deletion was also not a predictor of the breadth of the phenotypic spectrum, the severity of disease or prognosis of the patient. Although monosomies of 15q26 do not represent a classical contiguous gene syndrome, a few candidate genes for selected features such as proportional growth retardation and cardiac abnormalities have been identified. In 11 out of 16 patients with monosomy of distal 15q variable neurobehavioral phenotypes, including learning difficulties, seizures, attention-deficit-hyperactivity disorder, hearing loss and autism, have been found. We discuss clinical ramifications for cases with a loss of 15q26 detected by prenatal array-CGH.
O'Riordan AM, McGrath N, Sharif F, Murphy NP, Franklin O, Lynch SA, O'Grady MJ. Expanding the clinical spectrum of chromosome 15q26 terminal deletions associated with IGF-1 resistance. Eur J Pediatr. 2017 Jan;176(1):137-142. doi: 10.1007/s00431-016-2802-y. Epub 2016 Nov 8. PMID: 27826649.
Abstract
Haploinsufficiency of the insulin-like growth factor-1 receptor (IGF1R) gene on chromosome 15q26.3 is associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. Terminal deletions of chromosome 15q26 arising more proximally may also be associated with congenital heart disease, epilepsy, diaphragmatic hernia and renal anomalies. We report three additional cases of 15q26 terminal deletions with novel features which may further expand the spectrum of this rarely reported contiguous gene syndrome. Phenotypic features including neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been reported previously. Similarly, laboratory features of insulin-like growth factor 1 (IGF-1) resistance are described, including markedly elevated IGF-1 of up to +4.7 SDS. In one patient, the elevated IGF-1 declined over time and this coincided with a period of spontaneous growth acceleration.
Conclusion: Deletions of 15q26 are a potential risk factor for aortic root dilatation, neonatal lymphedema and aplasia cutis in addition to causing growth restriction. What is Known: • Terminal deletions of chromosome 15q26 are associated with impaired prenatal and postnatal growth, developmental delay, dysmorphic features and skeletal abnormalities. What is New: • Neonatal lymphedema, aplasia cutis congenita and aortic root dilatation have not been previously described in 15q26 terminal deletions and may represent novel features. • IGF-1 levels may be increased up to 4.7 SDS.
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