Distinctive Phenotypic Abnormalities Associated with Submicroscopic 21q22 Deletion Including DYRK1A.

[monosomy 21]

Partial monosomy 21 has been reported , but the phenotypes described are variable with location and size of the deletion . We present 2 patients with a partially overlapping microdeletion of 21 q 22 and a striking phenotypic resemblance . They both presented with severe psychomotor delay , behavioral problems , no speech , microcephaly , feeding problems with frequent regurgitation , idiopathic thrombocytopenia , obesity , deep set eyes , down turned corners of the mouth , dysplastic ears , and small chin . Brain MRI showed cerebral atrophy mostly evident in frontal and temporal lobes , widened ventricles and thin corpus callosum in both cases , and in one patient evidence of a migration disorder . The first patient also presented with epilepsy and a ventricular septum defect . The second patient had a unilateral Peters anomaly . Microarray analysis showed a partially overlapping microdeletion spanning about 2 .5 Mb in the 21 q 22 .1 -q 22 .2 region including the DYRK 1 A gene and excluding RUNX 1 . These patients present with a recognizable phenotype specific for this 21 q 22 .1 -q 22 .2 locus . We searched the literature for patients with overlapping deletions including the DYRK 1 A gene , in order to define other genes responsible for this presentation .

Diseases
Validation

Diseases presenting "obesity" symptom

acute rheumatic fever

adrenal incidentaloma

aniridia

aromatase deficiency

carcinoma of the gallbladder

cohen syndrome

congenital adrenal hyperplasia

cushing syndrome

cystinuria

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

familial hypocalciuric hypercalcemia

familial mediterranean fever

heparin-induced thrombocytopenia

kabuki syndrome

monosomy 21

phenylketonuria

primary hyperoxaluria type 1

sneddon syndrome

werner syndrome

wolf-hirschhorn syndrome

x-linked adrenoleukodystrophy

This symptom has already been validated