Fig 1 - uploaded by Yasemin Alanay
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Front view of the patient. Note eyebrows with prominent arch, V-shaped nasal tip, prominent columella, poorly formed cupid’s bow, thin upper lip, and brachymesophalangy of 4-5 involving both hands and feet.
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Chromosome 2q37 microdeletion syndrome is a rare disorder characterized by mild-moderate psychomotor and growth retardation, autistic-like behavior, Albright hereditary osteodystrophy-like metacarpal/metatarsal shortening, and facial characteristics. We here report on a patient with 2q37 microdeletion presenting with learning difficulty, hyperactiv...
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Context 1
... was the first child of nonconsanguineous parents. The family and prenatal histories were unremarkable. The patient was born at term with a birth weight of 3500 g (75-90th centile). She had head control at eight months of age, was able to sit with support at one year of age, without support at 18 months of age, and walk unaided at 24 months of age. She started speaking single words at 12 months of age and simple sentences at six years of age. Language and social skills were both markedly delayed. On physical examination, she weighed 22.5 kg (50th centile), and her height and head circumference were 121 cm (50-75th centile) and 50 cm (50th centile), respectively. Facial features such as eyebrows with prominent arch, V-shaped nasal tip, prominent columella, poorly formed cupid’s bow and thin upper lip, and brachymesophalangy of 4-5 involving both hands and feet, suggestive of an AHO-like phenotype, were noticed ( Fig. 1). Psychometric evaluation with Stanford-Binet Intelligence Scale revealed a score of 45-55. There was no evidence of congenital heart defect. Abdominal and renal ultrasonographies were normal. Audiological and ophthalmological assessments including fundus examination were both normal. Radiological evaluation confirmed brachymesophalangy of 4-5 involving both hands and feet. Osteopenia was not evident. Chromosome analysis revealed 46,XX (Fig. 2). Subtelomeric fluorescence in situ hybridization (FISH) analysis using ToTelVysion Multicolor FISH Probe Panel that applied the probe VIJyRM2112 (D2S447-) flanking 60 kb lying between 242.88-243.2 Mb on chromosome 2q37.3 revealed 46, XX.ish subtel(2q)(D2S447-) (Fig. 3). Maternal and paternal FISH analyses were normal ( de novo deletion). The clinical features of terminal microdeletions of 2q37 were first described in 1989 by Gorski et al. 5 The incidence is unknown, but more than 100 patients carrying isolated, primarily terminal deletions with breakpoint at or within chromosome 2q37 have been reported previously 1 . A minority of patients like the present patient show milder psychomotor and growth retardation and an AHO-like phenotype. Typical facial characteristics of AHO such as round face, prominent forehead, depressed nasal bridge, deficient nasal alar flare, deep-set eyes, upslanting palpebral fissures, and pinna anomalies were not present in this patient. However, it is well known and documented that patients with chromosome 2q37 microdeletion may have quite a variation in phenotype 1 , and the present patient does not appear to have the typical facial features. On the other hand, the key skeletal feature in this patient was brachymesophalangy. It is a variable but characteristic feature, which is reported in almost half of the patients with 2q37 microdeletion 1 . Defects in social interaction, hyperactivity, attention deficit, and sleep disturbances have all been described in 2q37microdeletion. Our patient had a short span of attention, hyperactivity and some repetitive behaviors. Patients with 2q37 microdeletions have milder cognitive deficits and are less likely to have major congenital abnormalities compared to patients with cytogenetically visible deletions. The present patient had ...
Citations
... This disease shows facial dysmorphism, including a prominent forehead; sparse, arched eyebrows; deep-set eyes; midface hypoplasia; a depressed nasal bridge; a thin upper lip; and various pinna anomalies, ranging from fleshy and/or anteverted lobules to microtia 3) . In addition, brachymetacarpia and brachymetaphalangia, typical signs of Albright hereditary osteodystrophy (AHO), are well described in 2q37 microdeletion syndrome 4) . In contrast to pseudohypoparathyroidism Ia or pseudopseudohypoparathyroidism, patients with 2q37 deletion syndrome do not have any mutations in GNAS, and they lack renal parathyroid hormone resistance and soft-tissue ossification 5) . ...
Chromosome 2q37 deletion syndrome is a rare chromosomal disorder characterized by mild to moderate developmental delay, brachydactyly of the third to fifth digits or toes, short stature, obesity, hypotonia, a characteristic facial appearance, and autism spectrum disorder. Here, we report on a patient with 2q37 deletion presenting with dilated cardiomyopathy (DCMP). Congenital heart malformations have been noted in up to 20% of patients with 2q37 deletions. However, DCMP has not been reported in 2q37 deletion patients previously. The patient exhibited the characteristic facial appearance (a flat nasal bridge, deep-set eyes, arched eyebrows, and a thin upper lip), developmental delay, mild mental retardation, peripheral nerve palsy, and Albright hereditary osteodystrophy (AHO)-like phenotypes (short stature and brachydactyly). Conventional chromosomal analysis results were normal; however, microarray-based comparative genomic hybridization revealed terminal deletion at 2q37.1q37.3. In addition, the patient was confirmed to have partial growth hormone (GH) deficiency and had shown a significant increase in growth rate after substitutive GH therapy. Chromosome 2q37 deletion syndrome should be considered in the differential diagnosis of patients presenting with AHO features, especially in the presence of facial dysmorphism. When patients are suspected of having a 2q37 deletion, high-resolution cytogenetic analysis is recommended.
The 2q37 deletion syndrome, also described in the literature as brachydactyly‐mental retardation syndrome (MIM 600430), is caused by deletion or haploinsufficiency of the HDAC4 gene, which encodes the histone deacetylase 4 protein. Although the most commonly described hallmark features of the 2q37 deletion syndrome include brachydactyly type E, developmental delay, obesity, autistic features, and craniofacial or skeletal dysmorphism, a literature review of 101 published cases plus two newly reported individuals indicates that there is a high degree of variability in the presence of some of the features that are considered the most characteristic of the syndrome: overweight and obesity (34%), cognitive‐behavioral issues (79%), dysmorphic craniofacial features (86%), and type E brachydactyly (48%). These features overlap with other neurodevelopmental conditions, including Smith‐Magenis syndrome (SMS), and may be incompletely penetrant or demonstrate variable expressivity, depending on the specific chromosomal anomaly. With the advent of fluorescence in situ hybridization (FISH), array‐based comparative genomic hybridization, and next‐generation DNA sequencing, more detailed molecular diagnoses are possible than in years past, enabling refined characterization of the genotype–phenotype correlation for subjects with 2q37 deletions. In addition, investigations into molecular and gene expression networks are expanding in neurodevelopmental conditions, and we surveyed HDAC4 downstream gene expression by quantitative real‐time polymerase chain reaction, further implicating HDAC4 in its role in the regulation of RAI1. Correlation of clinical data defining the impact on downstream gene expression and the potential clinical associations across neurodevelopment will improve our understanding of these complex conditions and potentially lead to common therapeutic approaches.
