Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome
Rare genetic disorder causing short stature and abnormal calcifications.
Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome is a rare genetic condition marked by bone abnormalities that lead to short stature and other health problems. Its features include a disproportionately short body, shortened arms and legs, small hands with broad, short fingers, a narrow chest with rib defects, a sunken chest, and abnormal calcifications in cartilaginous structures such as the larynx, trachea, and costal cartilages. Facial characteristics may involve a prominent forehead, widely spaced eyes, protruding eyes, a flat, short nose with wide nostrils, a high-arched palate, and a long philtrum. Spinal changes include flattened vertebrae, and X-rays show irregularities in the epiphyses and metaphyses. Without treatment, complications such as recurrent bacterial infections and spinal compression from atlantoaxial instability can be fatal, leading to early death.
The disorder is caused by autosomal recessive missense mutations in the DDR2 gene on chromosome 1. According to OMIM, about 24 cases have been reported in medical literature. The condition was first identified in 1993, when Borochowitz et al. described three patients from Sephardic Jewish (two cases) and Puerto Rican (one case) families, all with short stature, small limbs, a short nose with a wide bridge, broad nostrils, facial differences, and radiological anomalies. In one Sephardic Jewish family, both affected siblings died in infancy. That same year, Langer et al. reported eight patients with similar findings, including chest and sternum deformities, early abnormal cartilage calcification, and facial features; four died prematurely from spinal cord damage due to atlantoaxial instability. Seven of these eight patients were of Puerto Rican descent, and one family was consanguineous.
In 1996, Al-Gazali et al. described two siblings born to consanguineous Egyptian parents, both with generalized calcification of the epiphyses, ligaments, and cartilage, and normal intelligence. A 2010 follow-up by Ali et al. noted both died prematurely: one at age 8 from cord compression, the other at 13 from respiratory issues. In 2009, Bargal et al. reported eight patients, confirming that lower limb bowing and widespread calcifications worsen over time. Also in 2009, Smithson et al. described a 7-year-old Pakistani child with a milder form, and Dias et al.
Quick Facts
- Specialty
- Medical genetics, Pediatry
- Symptoms
- Osseous anomalies which result primarily in short stature
- Complications
- Death
- Onset
- Birth
- Duration
- Lifelong
- Causes
- Genetic mutation
- Risks
- Being of Puerto Rican descent, being part of a consanguineous family.
- Diagnosis
- This condition is diagnosed mainly through radiographs and sequencing of the DDR2 gene (gene responsible for the disorder).
- Differential
- Dwarfism, sudden infant death syndrome
- Prevention
- None
- Treatment
- treatment is done on the symptoms
- Prognosis
- Poor
Facts from the source article.
Lore & Background
The syndrome was first identified in 1993 when Borochowitz et al. described three patients with short stature, small upper and lower limbs, short nose with wide nasal bridge, broad nostrils, facial dysmorphisms, and radiological anomalies. These individuals were born into Sephardic Jewish (2 cases) and Puerto Rican families (1 case). In one Sephardic Jewish patient, both affected siblings died before reaching infancy. Later that year, Langer et al. described eight patients with similar radiological findings, including anterior thorax and sternum deformities, abnormal premature calcification in cartilaginous structures, and facial dysmorphisms. Seven of the eight patients came from Puerto Rican families, and one family was consanguineous. Four of the eight patients died prematurely due to cord damage induced by atlantoaxial instability.
Reader's Guide
Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome is significant as a rare genetic disorder that illustrates the severe consequences of mutations in the DDR2 gene. Its hallmark features include disproportionately short stature, shortened limbs, small hands with broad fingers, narrow chest, rib anomalies, and progressive calcifications of the larynx, trachea, and costal cartilages. The condition carries a high risk of premature death from recurrent bacterial infections or spinal compression due to atlantoaxial instability, as documented in multiple case series. The disorder has been reported in diverse ethnic groups, including Sephardic Jewish, Puerto Rican, Egyptian, and Pakistani families, with consanguinity noted in some cases. Its legacy lies in highlighting the importance of early diagnosis and management of spinal instability to prevent fatal cord compression, as well as demonstrating the progressive nature of the calcifications and limb bowing.
Did You Know?
- Approximately 24 cases have been described in medical literature according to OMIM.
- Four out of eight patients described by Langer et al. in 1993 died prematurely due to cord damage from atlantoaxial instability.
- One patient suffered from calcification of the falx cerebri at 20 months of age.
More in Growth disorders 1-24
Spotted an error? Know more?
Reader corrections go straight into our review queue. Suggest an edit · How this site is sourced