Background: Between the 6000 monogenic disorders, only few are due to a single mutation. Recently, a specific mutation has been described in TUBB3, encoding tubulin beta 3, in the association of Moebius syndrome (MS) and Kallmann syndrome (KS). MS is a congenital paralysis of eye and faces muscles and can be caused by mutations of TUBB3. KS combines hypogonadotropic hypogonadism and anosmia.
Objective and hypotheses: The combination of these two syndromes in the same patient is very rare. We report here a new case confirming that the association of MS and KS is due to the E410K mutation in TUBB3.
Method: MS has been diagnosed in a boy at the end of his first month of life because he had a facial paralysis, a micro retrognathism and suction difficulties. The diagnosis has been confirmed by an electromyogram of eye muscles. The hypodonadotropic hypogonadism has been brought up because of a micropenis and unilateral chryptorchidism, and it was confirmed at 3 months of life, with low gonadotropins, low testosterone and a negative LHRH test. Other pituitary axes were normal. Later in life, a psychomotor retardation appeared, as well as an epilepsy and a growth retardation. No puberty occurred spontaneously and the patient had an anosmia.
Results: The association between MS and KS led us to sequence the 4th exon of TUBB3. The results showed that the patient has a heterozygous mutation c.1228G>A in TUBB3 leading to the E410K substitution, whereas his mother and sister did not bear the mutation. We suspect a de-novo mutation.
Conclusion: The association of MS and KS is specifically due to a single mutation of TUBB3. Other mutations of TUBB3 cause MS only. The E410K substitution disturbs the tubulin beta 3 function in olfactory developing neurons whereas functional compensation occurs for other TUBB3 mutations in MS.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology