8p inverted duplication/deletion syndrome

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

8p inverted duplication/deletion [invdupdel(8p)] syndrome is a rare chromosomal anomaly characterized clinically by mild to severe intellectual deficit, severe developmental delay (psychomotor and speech development), hypotonia with tendency to develop progressive hypertonia and severe orthopedic problems over time, minor facial anomalies and agenesis of the corpus callosum.

Around 50 known cases have been reported. Prevalence is estimated at 1/22,000 to 1/30,000 births.

Most common clinical manifestations include developmental delay, mild to severe degree of cognitive deficit, lack or delay of expressive speech and language and hypotonia contributing to a severe psychomotor delay. Most children with invdupdel(8p) have been reported to be happy natured, sociable and communicative albeit non-verbal, but some may exhibit attention deficits, impulsivity and hyperactivity. Thirty to fifty percent of individuals with invdupdel(8p) have autism which varies greatly between individuals from very mild to severely autistic. Facial dysmorphism, more noticeable in childhood, are subtle and frequently include a prominent forehead, temporal baldness, anteverted nostrils, eversion of the lower lip, large mouth and ears and a short neck. Adults with invdupdel(8p) are normal to exceptionally tall and have a tendency to develop progressive hypertonia, spastic quadriplegia and severe orthopedic problems like contracted joints and scoliosis. Cardiac defects, eye abnormalities, urinary system anomalies, precocious puberty, high palate and abnormal dental development, as well as anomalies of extremities and dislocated hips have occasionally been reported.

An inverted duplication with a terminal deletion of the short arm of chromosome 8 mostly occurs as either an inverted duplication from centromere to D8S552 with a pter deletion from D8S349 or as an inverted duplication from 8p11.2 or 8p21 to D8S552, with a telomeric deletion from D8349. The input of the 8p deletion to the clinical picture appears less significant than the 8p inversion duplication rearrangement. To date, all invdupdel(8p) have occurred de novo.

Diagnosis is based on clinical manifestations and agenesis of the corpus callosum on brain magnetic resonance imaging (MRI) leading to chromosomal analysis. Molecular techniques may be used for the genetic characterization of the deletion (FISH, MLPA, CGH array).

Differential diagnosis includes other multiple congenital anomalies/intellectual deficit syndromes such as Trisomy 8p (see this term), in particular those with a 8p21-p22 duplication.

Antenatal diagnosis is based on echographic detection of fetal abnormalities (e.g. agenesis of corpus callosum) and cytogenetic analysis after amniocenteses or chorionic villus sampling.

Genetic counseling is recommended. Invdupdel(8p) rearrangements occur de novo. However, parents can carry a harmless common inversion involving the 8p23.1 segment (prevalence 1/4 to 1/5) which on rare occasions might lead to the more complex invdupdel(8p) rearrangement in their offspring.

There is no specific medical treatment. Physiotherapy from an early age as well as occupational therapy and speech therapy are recommended. Some patients benefit from music therapy. No gross orthopedic complications are noted. However, regular follow-up is needed.

There is no report on life expectancy. The majority of invdupdel(8p) individuals will need lifelong full-time care. Spastic quadriplegia may be slowly progressive with age.

Visit the Orphanet disease page for more resources.

Last updated: 1/1/2013

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