Clinical Description
Geleophysic dysplasia is a progressive disorder resembling a lysosomal storage disorder, involving bones and joints, cardiac valves, and skin. To date about 80 individuals have been reported: 33 affected individuals [Allali et al 2011] and 53 in case reports between 1960 and 2018 [Vanace et al 1960, Spranger et al 1971, Koiffmann et al 1984, Spranger et al 1984a, Spranger et al 1984b, Peters et al 1985, Lipson et al 1987, Shohat et al 1990, Wraith et al 1990, Lipson et al 1991, Rosser et al 1995, Figuera 1996, Hennekam et al 1996, Pontz et al 1996, Rennie et al 1997, Santolaya et al 1997, Titomanlio et al 1999, Keret et al 2002, Matsui et al 2002, Zhang et al 2004, Panagopoulos et al 2005, Scott et al 2005, Giray et al 2008, Ben-Salem et al 2013, Lee et al 2013, Porayette et al 2014, Elhoury et al 2015, García-Ortiz et al 2015, Mackenroth et al 2016, McInerney-Leo et al 2016, Li et al 2017, Cheng et al 2018].
Major findings are likely to be present in the first year of life.
A skeletal disorder is usually suspected at birth because of short stature and short hands and feet. The final height is between -3 SD and -6 SD. The progressive joint limitation and skin thickening interfere with normal joint function, leading to toe walking, contractions at large joints, and limitation of wrist and hand movement.
Cardiac findings are likely to become evident in the first year of life: 23/33 (70%) of affected children had cardiac anomalies (pulmonary stenosis, atrial septal defect) and had valvular thickening [Allali et al 2011; Authors, personal observation]; pulmonary arterial hypertension was observed in a few. The cardiac disease is progressive with dilation and thickening of the pulmonary, aortic, and mitral valves. Among those with valvular thickening, 30%-40% of affected children underwent valve replacement.
Intermittent hearing loss from otitis media is common.
Hepatomegaly, tracheal stenosis (observed in the first years of life in the more severe cases), and bronchopulmonary insufficiency with pulmonary arterial hypertension responsible for severe respiratory issues have also been observed. Note: Hepatomegaly is not associated with liver disease.
Two individuals developed glaucoma [Saricaoglu et al 2013; Author, personal data].
In the report of 33 individuals with ADAMTSL2-related geleophysic dysplasia, seven children (20%) died by age 3.6 years (average age 30 months) [Allali et al 2011]; a combination of cardiac, respiratory, and lung anomalies were reported.
The oldest living affected individual is age 30 years. In addition to progressive cardiac valvular thickening, survivors have short stature (< -3 SD), progressive joint contractures (limited range of motion of fingers, toes, wrist, and elbows, and tip-toe gait), thickened skin, and recurrent respiratory and ear infections.
Histologic examination of skin, liver, trachea, and heart shows lysosomal-like PAS-positive vacuoles, suggestive of glycoprotein and a storage disorder.