Giraldo‑Ocampo and Pachajoa ﻿BMC Pediatrics(2022) 22:569
https://doi.org/10.1186/s12887-022-03620-8Open Access

CASE REPORT

2q37 deletion syndrome in a Colombianpatient with macrocephaly: a case report
Sebastian Giraldo‑Ocampo1 and Harry Pachajoa2,3,4*   Abstract
Background: 2q37 deletion syndrome is a rare autosomal dominant disorder caused by deletions in the 2q37 cyto‑
bands leading to developmental delay, intellectual disability, behavioral abnormalities and dysmorphic craniofacialfeatures with more than 115 patients described worldwide.
Case presentation: We describe a Colombian 3-year-old patient with verbal communication delay, umbilical hernia,
facial dysmorphic features, hypotonia, and macrocephaly with normal magnetic resonance imaging. Microarraybased comparative genomic hybridization revealed a 5.9 Mb deletion in the 2q37.2 and 2q37.3 regions, eliminating
60 protein-coding genes in one of her chromosomes 2 and allowing the diagnosis of 2q37 deletion syndrome in thispatient. Therapeutic interventions so far were the surgical correction of the umbilical hernia.
Conclusions: Genetic tests are important tools for the diagnosis of clinically complex and infrequent conditions but
also for timely diagnosis that allows appropriate surveillance, interventions, and genetic counseling. This case also
provides information for expanding the phenotypical and genetic characterization of 2q37 deletion syndrome.
Keywords: Albright hereditary osteodystrophy-like syndrome (AHO-like), Brachydactyly-mental retardation
syndrome (BDMR), Macrocephaly, Case report
Introduction
2q37 deletion syndrome (del2q37, OMIM: 600430),
alternatively known as Albright hereditary osteodystrophy-like syndrome (AHO-like) or brachydactyly-mental retardation syndrome (BDMR), is a rare autosomal
dominant genetic disorder first reported in 1995 [1] andsince then, more than 115 cases worldwide have been
published [2]. It is characterized by developmental delay,
mild to moderate intellectual disability, behavioral abnormalities and dysmorphic craniofacial features [3]. Additional clinical manifestations include brachydactyly type
E in about half of the patients, short stature, obesity, seizures, hypotonia, structural abnormalities of the central
nervous system, the heart, trachea and gastrointestinal/*Correspondence: hmpachajoa@icesi.edu.co
3
Centro de Investigaciones en Anomalías Congénitas Y Enfermedades Raras(CIACER), Universidad Icesi, Calle 18 No. 122‑135 Pance, Cali, Colombia
Full list of author information is available at the end of the article

genitourinary tract in almost one-third of affected individuals [3, 4].
Although deletions reported in most patients affectmany genes, it seems that the loss of the Histone Deacetylase 4 (HDAC4) gene leads to haploinsufficiency
and drives the phenotype typically seen in these patients(brachydactyly type E, developmental delays, and Behavioral Problems) [5, 6]. HDAC4 protein is involved in awide variety of functions including gene transcription
regulation, cell growth, survival and proliferation, chondrogenesis, osteoblast differentiation, muscle development, neuronal survival, pancreatic beta/delta-celllineage specification and so on [7]. Given the low numberof patients described in the literature up to date, moredata describing the genotype–phenotype correlationof this syndrome is needed as well as the report of unusual symptoms that these patients may present. Here we
report one of the few Colombian patients diagnosed witha heterozygous deletion of 5.9 Mb in the subtelomeric© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, whichpermits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to theoriginal author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images orother third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line
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Giraldo‑Ocampo and Pachajoa ﻿BMC Pediatrics(2022) 22:569

region in the long arm of chromosome 2 leading to 2q37
deletion syndrome with a unique clinical manifestation:
macrocephaly.

Case presentation
A 3-year-old female patient was born to nonconsanguineous parents, a healthy mother and a father with macrocephaly, by cesarean section without complication. Birthweight was 4500 gr (> 97th percentile) and birth length
was 62 cm (> 97th percentile). Prenatal echography wasindicative of macrosomia. In the past, the mother had
four pregnancies with two different partners. In the firstone, a healthy male was born (half-brother of the patient)and the second pregnancy was interrupted due to a large
cystic hygroma in the fetal cranial base. The other two
pregnancies were with the father of the patient but oneof them was a miscarriage in the third semester with noclear cause. The patient did not crawl, presented sitting
posture at four months and walked at 18 months of age.
At 3 years old, physical examination revealed normal psychomotor development for the patient’s age but
presented a delay in verbal communication. The only
behavioral abnormality referred to by the mother was therising of arms in response to stimuli of joy and exaltation.
Additional features noticed were macrocephaly (head circumference of 53.5 cm, > 99th percentile); an umbilicalhernia, which was surgically corrected at 2 years of age; adefect of less than 1 cm in the abdominal wall; hypotonia
and several dysmorphic features such as prominent forehead and occiput, thin and upturned eyebrows, posteriorly rotated ears, flat nasal bridge, low hanging columella,thin upper lip, downturned corners of mouth and breast
hypertelorism. Hands and feet were normal. Weight was
18.5 kg (percentile 73) and length was 106 cm (percentile 81). Magnetic Resonance Imaging (MRI) of the brain,electromyography (EMG), echocardiogram and abdominal ultrasound were normal.
Conventional chromosome analysis (karyotype)revealed 46, XX and therefore a Microarray-based

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comparative genomic hybridization (array-CGH) wasperformed. A 5.9 Mb deletion was found in the distal orsubtelomeric region of the long arm of one of the chromosomes 2, comprising the genomic position 236869919
to 242782258, located in the 2q37.2 and 2q37.3 subbands (Fig. 1), allowing the diagnosis of chromosome
2q37 deletion syndrome (OMIM: 600430). Nearly 60
coding-protein genes are annotated in the National
Center for Biotechnology Information (NCBI) databasein the deleted region found in the patient. However, only
48 genes are annotated in the OMIM database, fromwhich, 11 genes are associated with different pathologies (Table 1). Currently, the patient attends kindergarten
and the mother reported a major improvement in verbal
communication as she grows.

Discussion and conclusions
We report a Colombian patient with a 5.9 Mb deletionin the 2q37 cytoband leading to 2q37 deletion syndrome. Del2q37 patients can present with a variable
set of clinical manifestations including major malformations (congenital heart and skeletal malformations,
gastrointestinal and renal anomalies and genitourinary
and central nervous malformations) in nearly 30% ofpatients; neurodevelopmental and behavioral anomalies like hypotonia, seizure, epilepsy and autisticfeatures that are frequently reported; typical facial dysmorphisms are reported in most cases and comprises
prominent forehead, depressed nasal bridge, thin upper
lip and arched eyebrows and late-onset abnormalities such as recurrent otitis and lower respiratory tract
infection, umbilical and inguinal hernias, articulation
dislocation, sparse or thin hair, joint laxity and eczema[8]. Our 3-year-old patient had the usual facial dysmorphism commonly reported, an umbilical hernia and adelay in verbal communication. The latter, as reportedby the mother, is improving considerably as the patient
grows. Aside from these manifestations, our patientpresented with macrosomia at birth and currently

Fig. 1 Map of the 2q37 deletion in the patient. Genes from chromosome bands 2q37.1 to 2q37.3 are shown. The map was create using UCSC
Genome Browser on Human (GRCh37/hg19). Black bar indicates the length of the deletion foundGiraldo‑Ocampo and Pachajoa ﻿BMC Pediatrics(2022) 22:569

Page 3 of 4

Table 1 Genetic alteration found in the patient and the genes deleted
ISCN 2016 formula

Type Zygosity

arr[GRCh37]
2q37.2q37.3(236869919_242782258) × 1LossSize (Mb) OMIM genes in the region

heterozygous 5.912

CNV classification

AGAP1, GBX2, ACKR3, COPS8, COL6A3, MLPH, PRLH, RAB17,Pathogenic
LRRFIP1, RAMP1, UBE2F, SCLY, ERFE, ILKAP, HES6, PER2, TRAF3IP1,ASB1, TWIST2, HDAC4, NDUFA10, COPS9, OTOS, GPC1, MIR149,RNPEPL1, CAPN10, GPR35, AQP12A, KIF1A, AGXT, SNED1, MTERF4,PASK, PPP1R7, ANO7, HDLBP, SEPTIN2, FARP2, STK25, BOK, THAP4,ATG4B, DTYMK, ING5, D2HGDH, GAL3ST2, NEU4

Genes written in bold and underline text are associated with different disorders in the OMIM databasepresents macrocephaly with normal MRI, conditions
not usually described as part of 2q37 syndrome.
Most of the genetic material loss in del2q37 patientsis de novo [2, 9] and therefore, their parents are healthy.
However, in some cases, polymorphisms of the 2qter
region are found in one of the healthy parents that may
predispose to important deletion in the 2q37 locationin the offspring [10]. Given the pregnancy history of
the patient’s mother and the macrocephaly also present in the father, further genetic testing (e.g., genome
or exome sequencing) in the patient and their parents
could give important information for genetic counseling and determining additional genetic changes in
the patient that may be associated with the symptoms
that she presents.
The deletion in the terminal region of one of thechromosome 2 in our patient led to the elimination of60 protein-coding genes (Fig. 1) including the HDAC4
gene which is one of the most important genes driving the symptoms in del2q37 patients [6]. Furthermore,
there is no clear association with length of deletion(as previously hypothesized) and clinical phenotype;even more, larger deletions (9.5 and 10.1 Mb) havebeen associated with higher IQ whereas smaller deletion with lower IQ (6.6 and 7.9 Mb) [11]. Deleted genes
in our patients also include genes that, in homozygosis, have been associated with different syndromes
and pathologies (Table 1) such as Bethlem myopathy
1 (gene COL6A3), advanced sleep phase syndrome(PER2), Barber-Say syndrome (TWIST2) and susceptibility to type 2 diabetes mellitus 1 (CAPN10) as
reported in OMIM database. However, due to the lackof information about which of these genes’ monosomy
are tolerated and which are not, no conclusions can bedrawn regarding their role in the phenotype.
Early diagnosis of del2q37 syndrome is importantbecause it provides information for appropriate surveillance, interventions and genetic counseling. Moreover,social and language skills can improve greatly with age, as
seen within a short time in our patient, making the syndrome more difficult to diagnose in later years [12]. Given
the broad range of clinical manifestations that del2q37

patients can present, a timely diagnosis of this disease, asin the presented case, will allow monitoring some of themost common as well as unforeseen complications. Forinstance, some del2q37 patients were reported to haveantibody deficiencies, leading to lower respiratory infection [6]. Therefore, our patient requires assessment andmonitoring by different medical specialties.
In Colombia, few del2q37 patients have been reportedwith important phenotypical differences from ourpatient. One was an 8-year-old female with brachydactyly type E, autism, developmental delay (including verbal communication), common dysmorphic features andmild tricuspid valve regurgitation [13]. The other was
an 18-year-old female with congenital heart malformations, developmental delay, autism, arachnodactyly anda concurrent pathogenic duplication in the 2p25.3p24.3
region [14].
In conclusion, we report a patient with a deletion of
5.9 Mb in the subtelomeric or distal region of the longarm of chromosome 2 and clinical manifestations compatible with del2q37 syndrome. Interestingly, this patient,
up to her age at the time of this case report (3 years old),
had a mild phenotype with only delay in verbal communication, umbilical hernia, hypotonia, facial dysmorphic
features and an unusual feature, macrocephaly. Given thetimely diagnosis, surveillance and management of complications can be addressed properly. This case provides
further information for expanding the phenotypic characterization of del2q37 syndrome.
Abbreviations
array-CGH: Microarray-based comparative genomic hybridization; del2q37:
Deletion in the 2q37 cytoband; HDAC4: Histone Deacetylase 4; NCBI: National
center for biotechnology information; Mb: Megabases.
Acknowledgements
The authors would like to thank the patient and her parents for agreeing tothe publication of this report. We also thank the people who have contributed
to the development and execution of this study.
Authors’ contributions
SG contributed to the acquisition of the data, drafted and revised the manu‑script, assisted with the design and the data analysis. HP cared for the patient,collected clinical information and designed the project. All authors read,edited and approved the final version of the manuscript.

Giraldo‑Ocampo and Pachajoa ﻿BMC Pediatrics(2022) 22:569

Funding
There is no funding to declare.
Availability of data and materials
The datasets used and/or analyzed during the current study are available fromthe corresponding author on reasonable request.

Declarations
Ethics approval and consent to participate
This study was approved by the Ethics Committee of Fundación Valle del Lili,Colombia (human study protocol #1504) and performed in accordance with
the Declaration of Helsinki. Written informed consent was obtained from theparents of the patient. Information revealing the subject’s identity was notincluded in the manuscript. The patient was identified by number and not by
his real name.
Consent for publication
Written informed consent for publication of clinical details and images/photo‑graphs was obtained from the parents of the patient.

Page 4 of 4

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Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in pub‑lished maps and institutional affiliations.

Competing interests
The authors declare no conflict of interest.
Author details
1Universidad del Valle, Cali, Colombia. 2 Genetics Division, Fundación Valle delLili, Cali, Colombia. 3 Centro de Investigaciones en Anomalías Congénitas Y
Enfermedades Raras (CIACER), Universidad Icesi, Calle 18 No. 122‑135 Pance,Cali, Colombia. 4 Centro de Investigaciones Clínicas, Fundación Valle del Lili,Cali, Colombia.
Received: 17 May 2022 Accepted: 16 September 2022

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