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Severe short stature due to 3-M syndrome with a novel OBSL1 gene mutation
Korcan Demir1, Ayça Altıncık, Ece Böber
1Department of Pediatric Endocrinology, Dokuz Eylul University, Izmir, Turkey.
Insights
3-M syndrome, a rare genetic disorder, causes severe growth retardation. This case highlights typical radiological findings and a novel mutation, aiding in diagnosis of this underdiagnosed condition.
Area of Science:
- Genetics
- Pediatrics
- Endocrinology
Background:
- 3-M syndrome is an autosomal recessive disorder.
- Characterized by severe growth retardation and distinct radiological features.
- Often underdiagnosed due to subtle initial presentation.
Observation:
- A patient presented with severe short stature and minimal dysmorphic features.
- Initial investigations including biochemistry, endocrine work-up, and karyotype were normal.
- Later evaluation revealed characteristic facial features, skeletal abnormalities, and delayed puberty.
Findings:
- Skeletal survey showed thin long bones with diaphyseal narrowing and tall lumbar vertebrae, typical for 3-M syndrome.
- Growth hormone therapy showed minimal efficacy.
- Genetic analysis identified a homozygous frameshift mutation (c.457_458delinsT) in the gene responsible for 3-M syndrome.
Implications:
- This case underscores the importance of recognizing characteristic radiological findings for diagnosing 3-M syndrome.
- Genetic confirmation is crucial for accurate diagnosis and genetic counseling.
- Further research into the molecular mechanisms of 3-M syndrome may reveal new therapeutic targets.
Abstract:
3-M syndrome is an underdiagnosed autosomal recessive disorder characterized by severe pre- and postnatal growth retardation with minimal dysmorphic features and distinguishing radiological findings. We report a patient who was first admitted at 7.5 years of age. He was born to consanguineous parents with a birth weight of 2250 g. Physical examination revealed a severe short stature (height, 95 cm; SD score -5.64) and minimal dysmorphic features. Biochemistry, endocrine work-up, and karyotype were normal. Reevaluation at 16.5 years of age revealed a height of 128.5 cm (SD score -5.27), prominent forehead, anteverted nasal openings, fleshy nasal tip, full lips, malar hypoplasia, hyperlordosis, prominent heels, testicular volumes 8-10 mL, and pubic hair consistent with Tanner stage II. Growth hormone trial for a year resulted in inadequate height gain (3 cm). The diagnosis of 3-M syndrome was made upon typical findings (thin long bones with diaphyseal narrowing and tall lumbar vertebrae) in a recent skeletal survey. Genetic analysis disclosed a homozygote frame shift mutation in exon 2: c.457_458delinsT resulting in p.Gly153fs.
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