ZTTK Syndrome in Early Childhood: A Case Report

We present the case of a 2-year-old girl born at 36+6 weeks of gestation by cesarean section due to intrauterine growth restriction and oligohydramnios. At birth, her anthropometric measurements were markedly reduced: weight 1860 g (-2.48 SDS), length 42 cm (-3.03 SDS), and head circumference 31 cm (-1.99 SDS). Postnatal cranial ultrasound revealed ventriculomegaly, whereas renal ultrasound and newborn screening were unremarkable. Echocardiography demonstrated a small persistent foramen ovale.
During follow-up, she developed progressive hearing impairment, muscular hypotonia, pronounced dystrophy with microcephaly, and global developmental delay. Motor milestones were delayed: rolling at 7 months, sitting at 18 months, and crawling at 23 months. At the age of 2 years, her expressive vocabulary was limited to approximately three words.
Exome sequencing identified a pathogenic heterozygous de novo variant in SON, confirming ZTTK syndrome. While core features such as microcephaly, hypotonia, growth restriction, and developmental delay are well documented in ZTTK, other manifestations in this patient such as progressive hearing loss are less frequently reported but should be considered in surveillance programs.
In summary, this case highlights the broad phenotypic variability of ZTTK syndrome and underscores the potential contribution of additional modifying genetic or non-genetic factors to the clinical presentation.