Pitt Hopkins syndrome: a rare cause of global neurodevelopmental delay

*Correspondence: [e-mail].

Abstract

Case Presentation: M.M, male, 1 year old, premature (34 weeks), low weight (1,525g), APGAR 8/10 and intrauterine growth restriction, sought evaluation due to developmental delay. On physical examination, hypertonia and accentuated reflexes were observed in the upper limbs. An investigation was initiated with a cranial MRI that showed agenesis of the corpus callosum. At 8 months of age, he returnsCOMP: Last name to care with a slight motor improvement after physiotherapy sessions, however, with speech delay and autistic patterns (non-symbolic play and stereotypies). Research with karyotype, BERA, ophthalmological evaluation and genetic and metabolic investigation followed. Diagnosed with myopia (7 degrees bilateral) with use of corrective lenses. Normal auditory evaluation, karyotype 46XY, screening for metabolic diseases without alterations. Genetic panel for normal movement disorders. He acquired some developmental milestones with the help of therapies, showing good social interaction, without very evident phenotypic changes, just a more pronounced nasal base. Requested CGH-Array with result compatible with Pitt Hopkins Syndrome (PTHS).

Discussion: PTHS is a neurodevelopmental disorder caused by the functional loss of an allele of the TCF4 gene that plays an important role in brain development. TCF4 encodes a transcription factor that controls the expression of other genes. It is characterized by phenotypic changes in the face (sunken eyes, prominent nose, wide mouth with widely spaced teeth), global developmental delay, and moderate to severe intellectual disability. Autistic symptoms and other behavioral changes are also common, although social interest is usually present. It may also be associated with respiratory and ophthalmological alterations (severe myopia, in most cases) and epilepsy. Subtle brain changes can be seen on imaging tests such as an underdeveloped corpus callosum.

Final Comments: PTHS is a rare disease with about 50 cases reported in Brazil. It should be suspected in children with developmental delay and speech impairment. Although craniofacial alterations are important features for the diagnosis, they may be less evident in childhood and, therefore, their absence does not exclude the disease. After the initial suspicion, the diagnosis can be established through molecular genetic testing. Treatment is stimulation with therapies, in addition to treating associated comorbidities.

 

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Artikel online veröffentlicht:
12. Mai 2025