UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients.
We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present in patients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck.
Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Nicole
N
de Leeuw
Saskia
S
Bulk
Andrew
A
Green
Lane
L
Jaeckle-Santos
Linda A
LA
Baker
Andrew R
AR
Zinn
Tjitske
T
Kleefstra
Jasper J
JJ
van der Smagt
Angela Maria
AM
Vianne Morgante
Bert B A
BB
de Vries
Hans
H
van Bokhoven
Arjan P M
AP
de Brouwer
D000015:Abnormalities, Multiple / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D012640:Seizures / Q000235:genetics*; D012868:Skin Abnormalities / Q000235:genetics; D013064:Speech Disorders / Q000235:genetics; D013577:Syndrome; D044763:Ubiquitin-Conjugating Enzymes / Q000172:deficiency / Q000235:genetics*; D014564:Urogenital Abnormalities / Q000235:genetics*
C471545:UBE2A protein, human; D044763:Ubiquitin-Conjugating Enzymes