Incontinentia pigmenti: learning disabilities are a fundamental hallmark of the disease.
Studies suggest that genetic factors are associated with the etiology of learning disabilities. Incontinentia Pigmenti (IP, OMIM#308300), which is caused by mutations of the IKBKG/NEMO gene, is a rare X-linked genomic disorder (1:10000/20:000) that affects the neuroectodermal tissues. It always affects the skin and sometimes the hair, teeth, nails, eyes and central nervous system (CNS). Data from IP patients demonstrate the heterogeneity of the clinical phenotype; about 30% have CNS manifestations. This extreme variability suggests that IP patients might also have learning disabilities. However, no studies in the literature have evaluated the cognitive profile of IP patients. In fact, the learning disability may go unnoticed in general neurological analyses, which focus on major disabling manifestations of the CNS. Here, we investigated the neuropsychological outcomes of a selected group of IP-patients by focusing on learning disabilities. We enrolled 10 women with IP (7 without mental retardation and 3 with mild to severe mental retardation) whose clinical diagnosis had been confirmed by the presence of a recurrent deletion in the IKBKG/NEMO gene. The participants were recruited from the Italian patients' association (I.P.A.SS.I. Onlus). They were submitted to a cognitive assessment that included the Wechsler Adult Intelligence scale and a battery of tests examining reading, arithmetic and writing skills. We found that 7 patients had deficits in calculation/arithmetic reasoning and reading but not writing skills; the remaining 3 had severe to mild intellectual disabilities. Results of this comprehensive evaluation of the molecular and psychoneurological aspects of IP make it possible to place "learning disabilities" among the CNS manifestations of the disease and suggest that the IKBKG/NEMO gene is a genetic determinant of this CNS defect. Our findings indicate the importance of an appropriate psychoneurological evaluation of IP patients, which includes early assessment of learning abilities, to prevent the onset of this deficit.
IRCCS, Santa Lucia Foundation, Rome, Italy.
Maria Rosa
MR
Pizzamiglio
IRCCS, Santa Lucia Foundation, Rome, Italy ; Life, Health and Environmental Science Department, University of L'Aquila, L'Aquila, Italy.
Laura
L
Piccardi
IRCCS, Santa Lucia Foundation, Rome, Italy ; Psychology Department, Sapienza University, Rome, Italy.
Filippo
F
Bianchini
IRCCS, Santa Lucia Foundation, Rome, Italy ; Psychology Department, Sapienza University, Rome, Italy.
Loredana
L
Canzano
IRCCS, Santa Lucia Foundation, Rome, Italy ; Psychology Department, Sapienza University, Rome, Italy.
Liana
L
Palermo
Institute of Genetics and Biophysics "Adriano Buzzati Traverso", Naples, Italy.
Francesca
F
Fusco
IRCCS, Santa Lucia Foundation, Rome, Italy.
Giovanni
G
D'Antuono
Clinical Genetics Unit, Obstetrics and Pediatric Department, Istituto di Ricovero e Cura a Carattere Scientifico, Arcispedale Santa Maria Nuova Hospital, Reggio Emilia, Italy.
Chiara
C
Gelmini
Clinical Genetics Unit, Obstetrics and Pediatric Department, Istituto di Ricovero e Cura a Carattere Scientifico, Arcispedale Santa Maria Nuova Hospital, Reggio Emilia, Italy.
Livia
L
Garavelli
Institute of Genetics and Biophysics "Adriano Buzzati Traverso", Naples, Italy ; Fondazione IRCCS SDN, Naples, Italy.
Matilde Valeria
MV
Ursini
D000328:Adult; D005260:Female; D006801:Humans; D007184:Incontinentia Pigmenti / Q000175:diagnosis*; D007859:Learning Disabilities / Q000175:diagnosis*; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult