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Título

AUTOSOMAL RECESSIVE PRIMARY MICROCEPHALY – 6 (MCPH6): A CASE REPORT

Apresentação do caso único

Preschooler, 4-year-old, female, presenting significant primary microcephaly and head circumference of 28 cm at birth. The patient exhibits global neurodevelopmental delay, with a prominent impairment in verbal communication. Currently, she expresses simple words and short sentences with phonetic simplifications, which are not easily understood by individuals outside her environment. Her motor development is slightly impaired for her age. In activities of daily living, she demonstrates limitations typical for her age group, with deficits in gross and fine motor coordination. The patient presents craniofacial disproportion, reduced forehead, frontal hypertrichosis, synophrys, arched eyebrows, tubular nose, micrognathia and facial hypotonia.
Neuroimaging revealed reduction in white matter, cerebral hemispheres with shallow sulci, mild and diffuse gyral simplification and megacisterna magna. Exome sequencing identified two pathogenic mutations in a heterozygous state in the CENPJ gene: chr13:24,912,736 G > GT p.Thr97Asnfs*7 ENST00000381884 and chr13:24,906,906 G > A p.Arg378* ENST00000381884. Molecular investigation confirmed the parents as carriers of the mutations. The child is currently undergoing PROMPT speech therapy with goals including variation in gestural language and symbolism, in addition to occupational therapy.

Discussão

Primary microcephaly-6 is an autosomal recessive condition where the CENPJ gene encodes a protein involved in regulation of microtubule assembly and nucleation.(1,2) Clinical manifestations are delayed language, slight motor delay, and mild to moderate intellectual disability.(1,3) Epilepsy and Attention Deficit Disorder may be present.
In the case, verbal communication is the most affected neurodevelopmental area. The inclusion in a specialized speech therapy for phonetic articulation, stimulation of gestural language and symbolism, provides specific resources to address the deficits. Motor delay was minimal, with developmental milestones below expectations, supporting the diagnosis of intellectual disability. Neuroimaging shows cortical gyral simplification, so she is under surveillance for epilepsy.

Comentários finais

Microcephaly can be isolated or associated with comorbidities. It is important to define the genetic etiology of primary microcephaly in order to establish individualized care with therapeutic guidance and monitoring for potential complications.(4) This approach aims to enhance quality of life and optimize available resources and potential.

Referências

(1) Microcephaly 6, Primary, Autosomal Recessive; MCPH6." OMIM, https://omim.org/entry/608393?search=Microcephaly%206%2C%20primary%2C&highlight=6%2Cmicrocephaly%2Cprimary. Accessed 10 Aug. 2024
(2) "Centrosomal Protein 152; CEP152." OMIM, https://omim.org/entry/609279. Accessed 10 Aug. 2024.
(3) Autosomal Recessive Primary Microcephaly 6." MedGen, U.S. National Library of Medicine, https://www.ncbi.nlm.nih.gov/medgen/330770. Accessed 10 Aug. 2024.
(4) Longo, Maria Gabriela, et al. "Brain imaging and genetic risk in the pediatric population, part 2: Congenital malformations of the central nervous system." Neuroimaging Clinics 25.1 (2015): 53-67.

Palavras Chave

Neurodevelopmental disorder; microcephaly; genetic disorder