Hyperphosphatasia with mental retardation syndrome type 1 in a child with seizures and craniofacial anomalies

Chwialkowska, K. (2024). Hyperphosphatasia with mental retardation syndrome type 1 in a child with seizures and craniofacial anomalies (Version 1) [DataSet]. GestaltMatcher Database.

We describe a 5-year-old male of European Eastern ancestry, born preterm at 35 weeks with birth weight and length above the 95th percentile, presenting with global neurodevelopmental delay, psychomotor retardation, aphasia, hypotonia, attention difficulties, and bilateral conductive hearing impairment. Clinical assessment revealed craniofacial dysmorphism characterized by macrocephaly, long eyelashes, ptosis, broad nasal bridge and tip, low-set ears, thin upper lip vermilion, and a high, narrow palate. Additional findings included obsessive-compulsive behaviors, autism spectrum disorder, sleep disturbance, seizures with abnormal EEG, impaired motor coordination, balance difficulties, sensory integration disorder, asymmetry of ventricular system on neuroimaging, elevated alkaline phosphatase, shortened distal phalanges with hypoplastic nails, and pigmentary retinopathy. Whole-exome sequencing identified a homozygous pathogenic variant in PIGV [NM_017837.4:c.1022C>A p.(Ala341Glu)], consistent with molecular diagnosis of hyperphosphatasia with mental retardation syndrome type 1 (HPMRS1) [MIM:239300]. The combination of core features such as intellectual disability, seizures, hypotonia, and biochemical evidence of hyperphosphatasia with additional manifestations including pigmentary retinopathy and obsessive-compulsive behaviors illustrates the broad phenotypic variability of this disorder. Recognition of these atypical associations is essential for early diagnosis, targeted management, and informed genetic counseling.