Rare but Recognisable !!!!!!!!!!!

Dr. Sree Lekshmy, Dr. Sheela Nampoothiri, Dr. Dhanya Yashodharan, Dr. C Jayakumar
 
Seven year old male child, presented due to short stature noticed since 2yrs of age. 
Vitals were stable and PICCLE was normal.
Auxology: 
Weight:14.8kg
Height:97cm (<3rd centile)
Head circumference:49.5cm
Lower segment (LS)-44.5cm
US:LS -1.17:1
Father’s height: 172cm
Mother’s height: 162cm
Mid parental height- 180cm
General examination showed dolicocephaly, flat nasal bridge, thick long eyelashes, high arched palate, severe brachydactyly of fingers and toes, bilateral 5th finger clinodactyly, cannot make a fist (bilateral 4th finger cannot be flexed), pectus excavatum, bilateral terminal elbow extension defect, bilateral supination defect. Cardiac status normal
WES sent showed a heterogenous known denovomutation in FBN1 gene suggestive of Geleophysic dysplasia type 2 . Family was counselled regarding associated short stature and the need for yearly cardiac and opthal evaluation.
 
Discussion: 
Introduction: 
Geleophysic dysplasia (GD) is a rare genetic skeletal dysplasia characterized distinct facial features, short stature, joint contracturesand cardiac features. The term “geleophysic” is derived from Greek, meaning “happy nature,” reflecting the cheerful appearance often associated with the condition. 
GD is a progressive disorder that can result in life-threatening complications, primarily due to cardiac and respiratory involvement.
Inheritance: 
Autosomal recessive manner, though some cases with autosomal dominant inheritance have been reported, particularly those involving mutations in the FBN1 gene. 
The disorder is caused mutations in genes such as ADAMTSL2, FBN1, and LTBP3, which are involved in extracellular matrix function and TGF-β signaling pathways.
Incidence:  Extremely rare condition, with fewer than 100 cases reported in the medical literature
Clinical Features: 
 
Skeletal Features:
-Short stature (disproportionate dwarfism).
-brachydactyly
-Progressive joint contractures, primarily in the fingers and larger joints.
 
Facial Features:
-A cheerful appearance resembling a “happy face.”
-Thickened skin and soft tissue.
 
Cardiac Features:
-Thickening of the mitral and aortic valves.
Respiratory Features:
-Tracheal stenosis
-Respiratory distress or infections due to airway obstruction.
Other Features: Hepatosplenomegaly (enlargement of liver and spleen) in some cases
 
Diagnosis: 
1. Clinical Assessment: Based on characteristic skeletal, facial, and systemic features.
2. Radiological Imaging: Shortened and thickened tubular bones. Advanced or irregular epiphyseal development.
3. Genetic Testing: Identification of pathogenic variants in ADAMTSL2, FBN1, or LTBP3 confirms the diagnosis.
4. Cardiac Evaluation: Echocardiography to assess valve thickening and function.
5. Skin Biopsy (Optional): May reveal abnormal extracellular matrix composition.
 
Management:
There is no definitive cure for GD; treatment focuses on symptom management and monitoring for complications:
 
1.Orthopaedic Care: Physical therapy to improve mobility and manage joint contractures. Surgical intervention for severe contractures or skeletal deformities.
2. Cardiac Management: Regular ECG monitoring. Medications or surgery for progressive valvular disease.
3. Respiratory Support: Management of tracheal stenosis and respiratory infections.
4. Genetic Counselling: to understand inheritance patterns and recurrence risks.
5. Multidisciplinary Care: Involvement of pediatricians, cardiologists, orthopedicians, and geneticists.