Relationship between macrocephaly and autism spectrum disorder in infancy

An arab four years old boy presented with macrocephaly and autism spectrum disorder (ASD). His father’s head circumference was 64 cm (> 97°C) without any significant behavioral problems. Skin lesions suspected of trichilemmomas was visible on the father’s face. His mother and two brothers had no macrocephaly or other dysmorphisms. The child was born at full term and all the auxological parameters were higher than the 97°C (weight 4365 g, height 55 cm, head circumference 38 cm) but during the boy’s growing up the skull’s circumference showed an increasing trend, going well above the 97°C. The child started to walk alone at 18 months and at 14 months he pronounced only a few words in arabic with a successive progressive language regression. At the age of 3 years and 6 months, a diagnosis of autism spectrum syndrome (ASD) was made. At physical examination, macrocephaly was confirmed (CC 57.5 cm, >97°C) while the other auxological parameters where in a lower range and he showed a characteristic habitus with elongated face shape, rounded forehead, downslanting palpebral fissures with hypertelorism, thin upper lip, pointed chin, angled, rotated auricles, no macroglossia, no skin spots and no other pathologic sign. Ophtalmological examination showed pseudopapilledema from papillary drusen. Brain MRI confirmed macrocephaly and excluded intracranial anomalies. A genetic analysis showed a nonsense variant in the PTEN gene in heterozygosity diagnosis of Cowden Syndrome (CS). The same variant was subsequently performed in the child’s parents showing the same mutation in the father. The child continued the neurodevelopmental and clinical-dermatological follow-up. The baby’s father instead began the oncological follow-up for the risk of developing colon cancer, renal cell carcinoma, papillary and follicular thyroid cancer.