Geleophysic Dysplasia 3

A number sign (#) is used with this entry because of evidence that geleophysic dysplasia-3 (GPHYSD3) is caused by heterozygous mutation in the LTBP3 gene (602090) on chromosome 11q13.

For a general phenotypic description and discussion of genetic heterogeneity of geleophysic dysplasia, see GPHYSD1 (231050).

Clinical Features

McInerney-Leo et al. (2016) studied a mother (SKDP-4.2) and 2 sons (SKDP-4.4 and SKDP-4.3) who had short stature, brachydactyly, restricted movements in the elbow and wrist joints, and dysmorphic facial features including round face, full cheeks, well-defined eyebrows, bulbous nose, anteverted nares, and thick lips. The mother underwent emergency tracheostomy after failed intubation for cesarean section; CT scan indicated probable preexisting subglottic stenosis. In addition, the younger son had a hoarse voice and subglottic stenosis, and echocardiogram at age 16 years showed mildly thickened mitral valve with mitral regurgitation, and possible pulmonary artery stenosis; however, these results were not confirmed on cardiac MRI. The family was clinically diagnosed with acromicric dysplasia (see 102370). The authors also reported 2 unrelated boys (GD-1 and GD-2) with facial features of geleophysic dysplasia, short stature, small hands and feet, stiff joints, thick skin, dyspnea, sleep apnea, tracheolaryngeal stenosis, and hepatomegaly. Both boys developed alveolointerstitial pneumonia and died of respiratory failure, at age 4 years and age 18 months, respectively.

Molecular Genetics

In a mother and 2 sons who showed features consistent with mild geleophysic dysplasia, McInerney-Leo et al. (2016) performed whole-exome sequencing and identified heterozygosity for a missense mutation in the LTBP3 gene (S696C; 602090.0008). In 2 unrelated boys diagnosed with geleophysic dysplasia but who were negative for mutation in the FBN1 (134797) and ADAMTSL2 (612277) genes, McInerney-Leo et al. (2016) identified heterozygosity for a stop-loss mutation (602090.0009) and a splice site mutation (602090.0010) in LTBP3, respectively.