Opitz GBBB Syndrome, X-linked - MID1

Klinische Symptomatik

X-chromosomal inherited Opitz-GBBB Syndrome is a rare inherited disorder characterized by multiple congenital centre-line defects.
Among the predominant clinical symptoms are the following:

• Craniofacial dysmorphism and deformity:

Prominent brow
Outward and upward/downward deviation of eyelids
Hypertelorism accompanied by telecanthus and/or epicanthus
Wide, flat bridge of the nose, anteverted nostrils
Cleft lip or cleft lip and palate, short frenulum
Retroverted ear onset
Long, flat philtrum, narrow upper lip, cleft uvula, tooth anomalies

• Urogenital anomalies:

Hypospadias, cryptorchidism, and Scrotum bifidum in males
Deformities of the larynx, pharynx and/or trachea (leading to swallowing and breathing difficulties) and rare ventral centre-line defects.

In addition to the abovementioned symptoms, heart defects (above all conotruncal defects) or brain deformities (hypoplasia or agenesia of the Corpus callosum) may also occur. Approximately two-thirds of affected patients have a mild to medium mental retardation; muscle hypotonia is also often observed. The prognosis for Opitz-GBBB Syndrome can be severe and severity may vary widely within a family.

Genetik

Opitz-G/BBB Syndrome is an autosomal dominant or X-chromosomal inheritance. In approximately 80% of cases with an X-chromosomal pattern of inheritance, mutations in the MID1 gene (Xp22.2) are also found. The gene codes for the Midline-1 Protein. Over 80 different mutations in the MID1 gene have been described. These mutations probably lead to a loss of function in the microtubule-associated MID1 protein; the pathogenesis is not yet clear.

 

Diagnostik