22q13.3 deletion syndrome: A recognizable malformation syndrome associated with marked speech and language delay

Abstract

The 22q13.3 deletion syndrome is a recognizable malformation syndrome associated with developmental delay, hypotonia, delayed or absent speech, autistic-like behavior, normal to accelerated growth and dysmorphic facies. The prevalence of this disorder is unknown, but it is likely under-diagnosed. Age at diagnosis has varied widely, from cases diagnosed prenatally to 46 years. Males and females are equally affected. The distal 22q deletion can be detected occasionally by routine or high resolution chromosome analysis; however, the majority of cases are detected by FISH analysis, associated with deletion of the ARSA (control) probe when performing a FISH analysis for the velocardiofacial syndrome (del 22q11.2). The 22q13.3 deletion syndrome can accompany a simple chromosome deletion, an unbalanced translocation, or a ring chromosome. Primary care physicians, in addition to numerous specialists, play an important role in caring for patients with this disorder. Although the dysmorphic features observed in this condition are nonspecific, it is an important consideration in the differential diagnosis of children with developmental delay, hypotonia, marked speech and language disability, autistic-like features, multiple minor anomalies, and normal growth and head circumference.

Phelan–McDermid Syndrome and SHANK3: Implications for Treatment

“…Developmental delays may not be apparent in the first 12 months of life, but a common presenting symptom in infants is hypotonia, which can also contribute to poor feeding, weak cry, and poor head control [43,51]. Low muscle tone and coordination deficits also contribute to significant delays in achieving major motor milestones like rolling over, crawling, and walking [46,[52][53][54]. The degree to which gross and fine motor coordination is affected in PMS can vary by location and severity, but gait is almost uniformly affected [10,43], with some reports of inability to ambulate [10,51].…”

Recurrent copy number changes in mentally retarded children harbour genes involved in cellular localization and the glutamate receptor complex

“…3 Although the very genetic heterogeneity of mental retardation renders genetic linkage and association studies difficult, chromosomal aberrations, occurring with an incidence of 1 per 120 newborns, 4 frequently provide a clue regarding the genetic locus underlying the phenotype of the affected child. Techniques allowing the detection of submicroscopic segmental aneuploidy have enabled us to pinpoint novel microdeletion and microduplication syndromes, such as CHARGE (coloboma, heart anomalies, chonal atresia, retardation, genital and ear anomalies), 5 Peters Plus, 6 recurrent 17q12 rearrangements, 7 del(17)(q21), 8,9 and the 22q13.3 deletion, 10 Pitt-Hopkins 11 and thrombocytopenia-absentradius syndromes 12 (for reviews see Lee and Lupski 3 and Slavotinek 13 ). In addition, clinically inconsequential segmental deletions [14][15][16] and segmental duplications in healthy individuals 17 have been reported.…”

Discovery of Rare Mutations in Autism: Elucidating Neurodevelopmental Mechanisms

“…There are also a number of microRNA-related loci in this region, including miR-185 and DiGeorge syndrome chromosomal (or critical) region 8, a component of the microprocessor complex that is involved in the initial step of miRNA biogenesis [110]. 22q13 22q13 deletion syndrome, also known as Phelan-McDermid syndrome, is characterized by global developmental delay, absent or severely delayed speech, ASD, neonatal hypotonia, normal or accelerated growth, and dysmorphic features [150,151]. Dysmorphic facial features include dolicocephaly, flat midface, wide nasal bridge, and bulbous nose.…”