Potocki-Lupski syndrome (PTLS) is characterized by cognitive, behavioral, and medical manifestations. Cognitively, most individuals present with developmental delay, later meeting criteria for moderate intellectual disability. Behaviorally, issues with attention, hyperactivity, withdrawal, and anxiety may be seen. Some individuals meet criteria for autism spectrum disorder. Medically, hypotonia, oropharyngeal dysphagia leading to failure to thrive, congenital heart disease, hypoglycemia associated with growth hormone deficiency, and mildly dysmorphic facial features are observed. Medical manifestations typically lead to identification of PTLS in infancy; however, those with only behavioral and cognitive manifestations may be identified in later childhood.

The 10q22.3-q23.2 region is characterized by a complex set of low-copy repeats (LCRs), which can give rise to various genomic changes mediated by nonallelic homologous recombination (NAHR). Recurrent deletions of chromosome 10q22.3-q23.2, including the BMPR1A gene (601299) have been associated with dysmorphic facies, developmental delay, and multiple congenital anomalies. Some patients with deletions that extend distally to include the PTEN gene (601728) have a more severe phenotype with infantile/juvenile polyposis, macrocephaly, dysmorphic facial features, and developmental delay (summary by van Bon et al., 2011).

IDDMSSD is a neurodevelopmental disorder characterized by impaired intellectual development, poor speech, postnatal macrocephaly, and seizures (Harms et al., 2018).

Lessel-Kreienkamp syndrome (LESKRES) is a neurodevelopmental disorder characterized by global developmental delay with intellectual disability and speech and language delay apparent from infancy or early childhood. The severity of the disorder is highly variable: some patients have mildly delayed walking and mild cognitive deficits, whereas others are nonambulatory and nonverbal. Most have behavioral disorders. Additional features, including seizures, hypotonia, gait abnormalities, visual defects, cardiac defects, and nonspecific dysmorphic facial features, may also be present (summary by Lessel et al., 2020).

Neurodevelopmental disorder with poor growth and behavioral abnormalities (NEDGBA) is an autosomal recessive disorder characterized by global developmental delay, moderately to severely impaired intellectual development, often with absent speech, and behavioral abnormalities, including hyperactivity, short attention span, and ADHD. Affected individuals show failure to thrive with poor overall growth; some have microcephaly. Additional features may include nonspecific facial dysmorphism, hypotonia, and feeding difficulties (Vogt et al., 2022; Meng et al., 2023).

Alfadhel syndrome (AFDL) is an autosomal recessive neurodevelopmental disorder with features of global developmental delay, hypotonia, and facial dysmorphism (Asiri et al., 2020, Bertoli-Avella et al., 2021).