Rare Diseases Symptoms Automatic Extraction

Duplication at Xq13.3-q21.1 with syndromic intellectual disability, a probable role for the ATRX gene.

[alpha-thalassemia]

Here we report on two unrelated male patients with syndromic intellectual disability (ID) due to duplication at Xq13.3-q21.1, a region of about 6 Mb and 25 genes. Among these, the most outstanding is ATRX, the causative gene of X-linked alpha-thalassemia/mental retardation. ATRX belongs to the growing list of genes implied in chromatin remodeling causing ID. Many these genes, such as MECP2, are dose-sensitive so that not only deletions and point mutations, but also duplications cause ID. Both patients have severe ID, absent expressive speech, early hypotonia, behavior problems (hyperactivity, repetitive self-stimulatory behavior), postnatal growth deficiency, microcephaly, micrognathia, cryptorchidism, low-set, posteriorly angulated ears, and downslanting palpebral fissures. These findings are also usually present among patients with loss-of-function mutations of the ATRX gene. Completely skewed X inactivation was observed in the only informative carrier mother, a constant finding among female carriers of inactivating point mutations of this gene. Participation of other duplicated genes cannot be excluded; nevertheless we propose that the increased dosage of ATRX is the major pathogenic mechanism of this X-linked disorder, a syndrome reminiscent of MECP2 duplication.

Diseases presenting "microcephaly" symptom

  • 22q11.2 deletion syndrome
  • alpha-thalassemia
  • coats disease
  • cohen syndrome
  • congenital toxoplasmosis
  • dentin dysplasia
  • hirschsprung disease
  • homocystinuria without methylmalonic aciduria
  • kabuki syndrome
  • monosomy 21
  • phenylketonuria
  • pyruvate dehydrogenase deficiency
  • severe combined immunodeficiency
  • wolf-hirschhorn syndrome

This symptom has already been validated