© 2018, GENASSIST, Inc.

By Keith S. Wexler, MBA, CFO, Business Development Director GENASSIST, Inc.

Paul Wexler, M.D., F.A.C.O.G., Medical Director, GENASSIST, Inc.

Clinical Professor, Department of OB/GYN, University of Colorado Health Sciences Center

Clinical Professor, Division of Genetics/Dept. of Pediatrics, Univ. of Colorado/The Children’s Hospital

Background:

A daughter of a patient was diagnosed with Pierre Robin Syndrome (PRS) as an infant and had a small jaw and repair of a cleft palate.  She has done very well.  She had no obstruction to her respiratory tract but did need tubes in her ears and had feeding problems until her cleft palate was repaired.

The patient’s father and brother had to have their tongues “clipped”. This history is consistent with ankyloglossia or a type of “tongue-tie”.  The patient’s nephew was diagnosed with incomplete fusion of his mandible which has not caused any significant difficulty.

Ankyloglossia (tongue-tie) can occur as part of the Pierre Robin Sequence but does not always accompany PRS. 

Analysis:

Pierre Robin Syndrome (PRS) is now usually referred to as Pierre Robin Sequence since only a single organ system is involved (face, mouth, jaw and palate). 

  • It has an incidence of approximately in 1 in 8,500 to 1 in 14,000. 

It can occur as a component of several syndromes including:

  • Trisomy 18
  • Trisomy 11q
  • Deletion 4q
  • Shprintzen Syndrome (Velocardiofacial Syndrome)
  • Charge Syndrome
  • Stickler Syndrome

However with those syndromes other organ systems are usually a significant part of the disorders.

Various candidate genes have been implicated in Pierre Robin Syndrome (PRS) as an isolated finding including the genes:

  • GAD67 on chromosome 2q31
  • PVRL1 gene on chromosome 11q23-24
  • SOX9 gene on 17q24.3-q25.1

However, since these are “only” candidate genes, preimplantation genetic diagnosis is Not a reasonable option at this time.

The history of facial abnormalities suggests the possibility that each of these disparate findings could represent an autosomal dominant condition passed from parent to each child.  This could place any children at up to a 1 in 2 (50%) risk for each child to manifest some degree of these facial, jaw and palatal changes.

One of the characteristics of an autosomal dominant condition inherited by getting one deleterious gene from an affected parent is variability in the severity of the condition.