OBJECTIVE: To determine the spectrum of clinical, neuropsychological, and neuroradiologic features in patients with autosomal recessive primary microcephaly (MCPH) due to ASPM gene mutations. METHODS: ASPM was sequenced in 52 unrelated MCPH probands. In patients with ASPM mutations, we evaluated the clinical phenotype, cognition, behavior, brain MRI, and family. RESULTS: We found homozygous or compound heterozygous ASPM loss-of-function mutations in 11 (22%) probands and 5 siblings. The probands harbored 18 different mutations, of which 16 were new. Microcephaly was severe after 1 year of age in all 16 patients, although in 4 patients the occipital-frontal circumference (OFC) at birth was decreased by only 2 SD. The OFC Z score consistently decreased after birth. Late-onset seizures occurred in 3 patients and significant pyramidal tract involvement in 1 patient. Intellectual quotients ranged from borderline-normal to severe mental retardation. Mild motor delay was noted in 7/16 patients. Language development was delayed in all patients older than 3 years. Brain MRI (n = 12) showed a simplified gyral pattern in 9 patients and several malformations including ventricle enlargement (n = 7), partial corpus callosum agenesis (n = 3), mild cerebellar hypoplasia (n = 1), focal cortical dysplasia (n = 1), and unilateral polymicrogyria (n = 1). Non-neurologic abnormalities consisted of short stature (n = 1), idiopathic premature puberty (n = 1), and renal dysplasia (n = 1). CONCLUSIONS: We provide a detailed description of features associated with ASPM mutations. Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly

Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations / Passemard, S; Titomanlio, L; Elmaleh, M; Afenjar, A; Alessandri, Jl; Andria, Generoso; de Villemeur, Tb; Boespflug Tanguy, O; Burglen, L; DEL GIUDICE, Ennio; Guimiot, F; Hyon, C; Isidor, B; Mégarbané, A; Moog, U; Odent, S; Hernandez, K; Pouvreau, N; Scala, Iris; Schaer, M; Gressens, P; Gerard, B; Verloes, A.. - In: NEUROLOGY. - ISSN 0028-3878. - STAMPA. - 73:12(2009), pp. 962-969.

Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations

ANDRIA, GENEROSO;DEL GIUDICE, ENNIO;SCALA, IRIS;
2009

Abstract

OBJECTIVE: To determine the spectrum of clinical, neuropsychological, and neuroradiologic features in patients with autosomal recessive primary microcephaly (MCPH) due to ASPM gene mutations. METHODS: ASPM was sequenced in 52 unrelated MCPH probands. In patients with ASPM mutations, we evaluated the clinical phenotype, cognition, behavior, brain MRI, and family. RESULTS: We found homozygous or compound heterozygous ASPM loss-of-function mutations in 11 (22%) probands and 5 siblings. The probands harbored 18 different mutations, of which 16 were new. Microcephaly was severe after 1 year of age in all 16 patients, although in 4 patients the occipital-frontal circumference (OFC) at birth was decreased by only 2 SD. The OFC Z score consistently decreased after birth. Late-onset seizures occurred in 3 patients and significant pyramidal tract involvement in 1 patient. Intellectual quotients ranged from borderline-normal to severe mental retardation. Mild motor delay was noted in 7/16 patients. Language development was delayed in all patients older than 3 years. Brain MRI (n = 12) showed a simplified gyral pattern in 9 patients and several malformations including ventricle enlargement (n = 7), partial corpus callosum agenesis (n = 3), mild cerebellar hypoplasia (n = 1), focal cortical dysplasia (n = 1), and unilateral polymicrogyria (n = 1). Non-neurologic abnormalities consisted of short stature (n = 1), idiopathic premature puberty (n = 1), and renal dysplasia (n = 1). CONCLUSIONS: We provide a detailed description of features associated with ASPM mutations. Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly
2009
Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations / Passemard, S; Titomanlio, L; Elmaleh, M; Afenjar, A; Alessandri, Jl; Andria, Generoso; de Villemeur, Tb; Boespflug Tanguy, O; Burglen, L; DEL GIUDICE, Ennio; Guimiot, F; Hyon, C; Isidor, B; Mégarbané, A; Moog, U; Odent, S; Hernandez, K; Pouvreau, N; Scala, Iris; Schaer, M; Gressens, P; Gerard, B; Verloes, A.. - In: NEUROLOGY. - ISSN 0028-3878. - STAMPA. - 73:12(2009), pp. 962-969.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/356369
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