**Question:** In Millard Gubler syndrome, all are involved except

A. Respiratory system
B. Circulatory system
C. Gastrointestinal system
D. Urinary system

**Core Concept:** Millard Gubler syndrome is a rare genetic disorder characterized by multiple congenital anomalies. It is caused by mutations in the FGFR3 gene, which encodes a protein involved in cell growth and differentiation during embryonic development. This syndrome is associated with a wide range of abnormalities, including:

**Why the Correct Answer is Right:** Among the given options, the urinary system is not directly involved in the FGFR3 gene functions or its downstream effects. The respiratory system, circulatory system, and gastrointestinal system are all affected by the genetic mutation. The FGFR3 protein plays a crucial role in the development of these systems, leading to the abnormalities observed in Millard Gubler syndrome.

**Why Each Wrong Option is Incorrect:**

A. Respiratory system: The FGFR3 gene mutation can lead to impaired development of the respiratory system, resulting in respiratory distress and hypotonia (low muscle tone).
B. Circulatory system: The mutation can lead to abnormal development of the cardiovascular system, causing congenital heart defects and other cardiovascular issues.
C. Gastrointestinal system: The FGFR3 gene mutation affects the development of the gastrointestinal system, leading to malformations such as intestinal atresia and mega-colon.
D. Urinary system: As mentioned earlier, the urinary system is not directly affected by the FGFR3 gene mutation, although renal hypoplasia can occur as a result of generalized developmental abnormalities.

**Clinical Pearl:** Understanding the effects of Millard Gubler syndrome on different organ systems is crucial for healthcare providers to identify the syndrome and provide appropriate diagnosis and management strategies for affected individuals. It highlights the importance of genetic testing and counseling in understanding the underlying causes of congenital anomalies and guiding therapeutic interventions.

In summary, Millard Gubler syndrome involves multiple organ systems, including respiratory, circulatory, gastrointestinal, and skeletal systems. The urinary system is not directly affected, although renal hypoplasia can occur as a result of generalized developmental abnormalities.