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Shprintzen syndrome

22q11.2 deletion syndrome (also called DiGeorge syndrome and velocardiofacial syndrome) is a disorder caused by the deletion of a small piece of chromosome 22. The deletion occurs near the middle of the chromosome at a location designated q11.2. more...

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The features of this syndrome vary widely, even among members of the same family, and affect many parts of the body. Characteristic signs and symptoms include heart defects that are often present from birth, an opening in the roof of the mouth (a cleft palate or other defect in the palate), learning disabilities, recurrent infections caused by problems with the immune system, and mild differences in facial features. Affected individuals may also have kidney abnormalities, low levels of calcium in the blood (which can result in seizures), significant feeding difficulties, autoimmune disorders such as rheumatoid arthritis, and an increased risk of developing mental illnesses such as schizophrenia and bipolar disorder.

Because the signs and symptoms of 22q11.2 deletion syndrome are so varied, different groupings of features were once described as separate conditions. Doctors named these conditions DiGeorge syndrome, velocardiofacial syndrome (also called Shprintzen syndrome), and conotruncal anomaly face syndrome. In addition, some children with the 22q11.2 deletion were diagnosed with Opitz G/BBB syndrome and Cayler cardiofacial syndrome. Once the genetic basis for these disorders was identified, doctors determined that they were all part of a single syndrome with many possible signs and symptoms. To avoid confusion, this condition is usually called 22q11.2 deletion syndrome, a description based on its underlying genetic cause.


Individuals with a 22q11 deletion have a range of findings, including:

  • Congenital heart disease (74% of individuals), particularly conotruncal malformations (tetralogy of Fallot, interrupted aortic arch, ventricular septal defect, and truncus arteriosus)
  • palatal abnormalities (69%), particularly velopharyngeal incompetence (VPI), submucosal cleft palate, and cleft palate; characteristic facial features (present in the majority of Caucasian individuals)
  • learning difficulties (70-90%)
  • an immune deficiency regardless of their clinical presentation (77%)
  • hypocalcemia (50%)
  • significant feeding problems (30%)
  • renal anomalies (37%)
  • hearing loss (both conductive and sensorineural)
  • laryngotracheoesophageal anomalies
  • growth hormone deficiency
  • autoimmune disorders
  • seizures (without hypocalcemia)
  • skeletal abnormalities

Thymus, parathyroid glands and heart derive from the same primitive embryonic structure and that is why these three organs are dysfunctioned together in this disease. Affected patients (usually children) are prone to yeast infections.


The disease is related with genetic deletions (loss of a small part of the genetic material) found on the long arm of the 22nd chromosome. Some patients with similar clinical features may have deletions on the short arm of chromosome 10.


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speech-language pathologist: Key role in the diagnosis of velocardiofacial syndrome, The
From American Journal of Speech-Language Pathology, 2/1/99 by Carneol, Susan Oliff

Velocardiofacial syndrome (VCF) is a genetic condition involving palate abnormalities, cardiac anomalies, characteristic facies, and learning disabilities. This autosomal dominant malformation pattern is one of the most common syndromes associated with clefting (Shprintzen, Goldberg, Young, & Wolford, 1981), yet it can easily go undiagnosed. Velopharyngeal inadequacy is one of the key features. Because of the high incidence of speech, voice, and language disorders found in this population, the speech-language pathologist plays an integral role in the diagnosis of the syndrome and assists in management decisions related to medical and/ or educational issues.

The purposes of this paper are to: (a) inform

the reader of the expanding phenotype of velocardiofacial syndrome, (b) inform the reader of the ramifications of an accurate and early diagnosis, and (c) highlight the role the speechlanguage pathologist plays in the diagnosis of this genetic syndrome. This will be accomplished with a review of current literature and a case study presentation of a family with VCF who was evaluated at the Masters Family Speech and Hearing Center and Cleft Palate Center at Children's Hospital of Wisconsin.

Key Words: velocardiofacial syndrome, cleft palate and craniofacial anomalies, genetic disorders, hypernasal resonance, syndromes in school-age children

The original phenotype of velocardiofac:ial syndrome (VCF) was first described by Sedlockova in 1967. It was further delineated by Shprintzen et al. in 1978, at which time 12 cases were presented with similar features of hypernasal speech secondary to cleft palate, typical facies, congenital heart anomalies, and learning disabilities or mental retardation. A typical appearance included a long face, malar flatness, long tubular nose, narrow palpebral fissures, and a small mouth (Figure 1). This phenotype has rapidly expanded over the past decade. Recent literature indicates the confirmation of the syndrome can exceed its initial hallmark boundaries of palate, cardiac, and facial symptomatology (Goldberg, Motzkin, Marion, Scambler, & Shprintzen, 1993) and that the diagnosis can be made in the absence of one or two of the cornerstone features (Finkelstein et al., 1993; Haapanen & Somer, 1993; Lipson et al., 1991; Weik, Carneol, Marks, Denny, & Beste, 1993).

Although a chromosome microdeletion (22q11 deletion) has been identified in most patients, to date there is no one specific finding that will lead to a definitive diagnosis (Morrow, Goldberg, Carlson, Kucherlapati, & Shprintzen, 1996). Furthermore, criteria have not been set to determine the number of major and minor features needed to implicate the diagnosis. Because of this it is necessary to rely on a gestalt impression. When a suspicion is raised, further assessment should be pursued. Although diagnosis is dependent on a number of structural anomalies and cognitive/psychological findings, the variability of the features and the frequent minor degree of manifestation may lead to underidentification of the condition, even among specialists in the area of cleft palate and craniofacial anomalies (Lipson et al., 1991; Weik et al., 1993).

Because of the high incidence of speech/resonance disorders and learning disabilities among this population, the speech-language pathologist may be the most likely (and sometimes the first) professional to interface with these individuals. Speech-language pathologists by nature of their professional education, training, and experience are unique in their ability to evaluate the total client profile: organic variables, behavioral issues, communication skills, academic achievement, and learning styles. It behooves the speech-language pathologist, regardless of work setting (i.e., hospitals, schools, private practice, etc.), to be vigilant in diagnostic endeavors to identify salient information that can lead to the diagnosis of velocardiofacial syndrome. Early diagnosis should lead to better treatment of communication and educational deficits and aid in medical diagnosis and management decisions.

Literature Review of Syndrome Features Velopharyngeal Features: Palatal Anomalies and/or Hypernasality

In a study of 120 patients with VCF, Goldberg et al. ( 1993) reported that structural clefting disorders (i.e., clefts of the secondary palate, submucous cleft palate, and occult submucous1 cleft palate) occurred 98-100% of the time in the VCF population. Two other studies indicated only 5661% of the patients with VCF presented with structural clefting disorders (Haapanen & Somer, 1993; Weik et al., 1993). In these studies, some palate anomalies were minor. These included: submucous cleft palate, occult submucous cleft, and a microform2 of a cleft. Unilateral palatal paresis also was reported by Weik et al. and by Riski, Armfield, Krause, Cohen, and Burstein, 1997. In summary, a structural palate anomaly may or may not be observable in an individual with velocardiofacial syndrome. In fact, 15 of 20 patients at Scottish Rite Children's Medical Center in Atlanta, Georgia had no visible signs of clefting (J. E. Riski, personal communication, February 21, 1998).

A more consistent finding cited in the VCF literature is velopharyngeal inadequacy (VPI). This is a generic term used to denote any variety of velopharyngeal dysfunction (Trost, 1983). Multiple variables and their interrelations account for VPI in individuals with velocardiofacial syndrome. These variables include: clefting, short velum, deep retropharynx (due to platybasia, an obtuse angulation of the cranial base), palatal weakness and incoordination, reduced lateral wall function, and pharyngeal hypotonia (Arvystas & Shprintzen, 1984; Bak et al., 1994; Glander & Cisneros, 1992; Shprintzen et al., 1981). Hypernasality is the primary indicator of VPI. Although it is a key feature in the VCF literature, the severity level ranges from severe hypernasality (VCF Fact Sheet, 1997) to minimal or none (Haapanen & Somer, 1993; Lipson et al., 1991; Weik et al., 1993). Speech correlates of VPI include reduced intraoral breath pressure, nasal emission, and compensatory articulation errors. Again, there is great variability in the degree of severity for these speech characteristics, ranging from severe to slight or normal (Lipson et al., 1991; VCF Fact Sheet, 1997; Weik et al., 1993).

When there is no evidence of physical findings and no obvious nasal resonance, it may be that VPI is present but the nasality is masked by hoarseness, high pitch or other voice characteristics. Sometimes it is via case history information that either VPI or VCF is suspected. This history information includes infant feeding difficulties characterized by weak suck, nasal regurgitation, and need for frequent burping, as well as history of gastroesophageal reflux and recurrent ear infections (VCF Fact Sheet, 1997).

In contrast to the early literature, the diagnosis of velocardiofacial syndrome can be made without obvious clefting and little to no perceptible hypernasality (Haapanen & Somer,1993; Lipson et al., 1991; Weik et al.,1993). This will be illustrated in the subsequent case presentations.

Cardiac Features and Vascular Findings

Congenital cardiac anomaly, considered to be one of the keystone features of the syndrome in the earliest literature, is now described in varying degrees of occurrence and severity of anomaly. Incidence values range from 82% (Goldberg et al., 1993) to 39% (Weik et al., 1993). Major cardiac findings include: ventral septal defects (VSD), tetralogy of Fallot3, and right-sided aortic arch defects. Less common findings include: vascular rings, pulmonary stenosis, and/or atrial septal defect (Finkelstein et al., 1993; Lipson et al., 1991; Weik et al., 1993).

Facial Features

The most striking similarity and most consistent diagnostic indicator for VCF is the common facial appearance; but this aspect, too, reflects some variability (Finkelstein et al., 1993). As demonstrated in Figure 2a and 2b, the characteristic appearance is a long face with a flat malar region, long prominent nose with or without a broad nasal bridge and bulbous tip, narrow palpebral fissures, slanted eyes, small mouth, micrognathia, retrognathia, external ear anomalies, and abundant scalp hair (Finkelstein et al., 1993; Shprintzen et al., 1981).

Review of infant and toddler patient profiles suggests a different pattern of facial features that may allow for an earlier diagnosis of the syndrome. This includes a short hypoplastic midface with or without epicanthic folds and/ or small palpebral fissures, relatively short nose with a prominent bridge and a bulbous tip, a long philtrum and chin deficiency, and a small mouth with thin down-turned corners of the upper lip. These observations suggest an evolution in the development of the "classic" VCF face, with the younger face having its own recognizable features (Weik et al., 1993) (Figures 3a, 3b, 3c, 4a, 4b).

Oral Motor, Communication, and Cognitive Features

Speech. In addition to the speech and voice correlates associated with velopharyngeal inadequacy, individuals with VCF can demonstrate articulation/phonological disorders not associated with VPI. These include phonological delays/ disorders, dysarthria and dyspraxia of speech, and high pitched voice (Riski et al., 1997; VCF Fact Sheet, 1997). No fluency disorders have been reported.

Feeding. Clinical experience and training indicate that children are at risk for feeding problems if they present with any of the following in isolation or in combination: generalized hypotonia, cardiac problems, upper airway obstruction, and/or VPI. Not surprisingly, infant feeding difficulties are associated with the VCF population (VCF Fact Sheet, 1997). Pharyngeal hypotonia, found in 90% of the VCF population (Shprintzen et al.,1981), correlates with generalized hypotonia and is found in association with swallowing and other oral motor problems.

Hearing. Hearing loss has been reported in individuals with VCF, the majority being conductive loss secondary to otitis media (Shprintzen et al., 1981). Ossicular chain malformations have also been reported (Weik et al., 1993). A smaller percentage of sensorineural losses have been cited (VCF Fact Sheet, 1997).

Language, Cognition, and Pragmatics. Learning disabilities (LD) and/or mild cognitive disabilities are among the most common features of the syndrome, occurring in 99% of the patient population (Goldberg et al., 1993). One study (Golding-Kushner, Weller, & Shprintzen, 1985) indicated that perceptual motor weakness was evident in children with VCF regardless of age. However, intellectual functioning and language ability changed over time even though both were relatively normal before age 6. The children stayed at a relatively concrete cognitive level as they got older, resulting in poor abstract reasoning skills. This resulted in increasingly poorer psychological, language, and academic performances with age. These individuals had difficulty dealing with more abstract cognitive and linguistic demands in various academic and social situations. These students are often the "gray area" students who do not meet criteria for special education services in the public schools, but still present with functional communication and learning deficits. Because many children with VCF also have a history of recurrent otitis media with effusion, they are even more at risk for speech and language delays and academic difficulties (Faires, Topping, & Cranford, 1993; Gravel & Wallace, 1996).

In addition, recent studies indicate the development of various psychiatric disorders in some adolescents and adults with VCF, including attention-deficit hyperactivity disorder, generalized anxiety disorder, major depressive disorder, manic depressive disorder, paranoid schizophrenia, obsessive compulsive disorder, paranoid disorder, and severe personality disorder (Goldberg et al., 1993). A flat affect has been another common characteristic found in the literature.

Other Features

As stated previously in this paper, diagnosis of velocardiofacial syndrome relies on documenting clusters of major and minor characteristics. Given the variability of the types and degree of manifestation of the hallmark features, these documentations become tantamount in confirming a diagnosis. Other physical findings include eye abnormalities such as tortuous retinal vessels, generalized hypotonia, abdominal/kidney abnormalities, small hands and long digits, short stature, fine and gross motor problems, immunological dysfunction as reflected by frequent upper respiratory infections and lower airway disease, and endocrine problems such as hypocalcemia and hypothyroidism (VCF Fact Sheet, 1997).

Comorbidity of other syndromes or sequences also have been reported. Recent literature has identified overlapping genetic markers for VCF and DiGeorge sequence (Goldberg et al., 1993; Matzkin, Marion, Goldberg, Shprintzen, & Saenger, 1993; Stevens, Carey, & Shigeoka,1990). This suggests that some individuals with DiGeorge sequence may also have velocardiofacial syndrome. In addition, 15% of patients with Pierre Robin sequence have VCF (Shprintzen, 1988). Should case history or current evaluation information indicate the presence of DiGeorge or Pierre Robin sequence, further evaluation of VCF is needed.

Ramifications of Diagnosis

An early and accurate diagnosis of VCF makes prevention and early intervention possible for all areas affected by the diagnosis: the child's health, development, social and emotional well being, and academic success. The diagnosis of velocardiofacial syndrome should influence the speechlanguage pathologist's input for VPI management, referrals for recurrent otitis media and other voice disorders, and educational programming. Mistakes can be made without an accurate diagnosis of this syndrome. The following ramifications should be considered.

VPI Management

Early correction of velopharyngeal inadequacy is desirable to ward off use or development of compensatory articulation errors and improve overall speech intelligibility. VPI causing hypernasality (that is not phoneme specific) is generally not responsive to voice therapy. It is best treated with a surgical or prosthetic approach. Decisions regarding surgical or prosthetic management are typically made by a cleft palate team when the child is between the ages of 2-1/2 and 6 years. Given that time range, an early diagnosis of velocardiofacial syndrome can prevent or ameliorate potential surgical complications and/ or determine the need for interim prosthetic management. Multiple factors must be investigated to ensure appropriate intervention strategies and pre- and postoperative surgical care. This includes the degree of cardiac involvement, aberrant blood vessels, pharyngeal hypotonia, and upper airway obstruction.

For patients with a confirmed diagnosis of VCF, the degree of cardiac involvement may contraindicate or postpone surgical management. The use of a speech prosthesis might be considered for these patients. The diagnosis of VCF should alert the surgeon to further investigate the status of the blood vessels to rule out tortuosity, which may result in unnecessary bleeding difficulties during surgery.

Incidence of aberrant blood vessels in the VCF population has been reported to be between 14-26% (Finkelstein et al., 1993; Goldberg et al., 1993; MacKenzie-Stepner et al., 1987; Weik et al., 1993). The presence of tortuous or ectopic arteries implies obvious risks of excessive bleeding with any form of pharyngoplasty and caution should be exercised in determining and implementing appropriate surgical or prosthetic management procedures. Displacement of internal carotid arteries could be identified on endoscopic examination and confirmed through magnetic resonance angiography (Mitnick & Shprintzen, 1996).

Pharyngeal hypotonia has been correlated with the presence of generalized hypotonia, history of swallowing problems, and other oral motor dysfunction. It has been described frequently in the VCF population. Pharyngeal hypotonia can contribute to postsurgical obstructive sleep apnea (OSA). OSA has accounted for one known death in a patient with VCF following pharyngeal flap surgery (Shprintzen et al., 1978). Wide pharyngeal dimensions and poor lateral pharyngeal wall motion typically require a broad pharyngeal flap. The combination of the airway obstruction and potential of collapse of the pharyngeal wall with any introduction of negative pressure in the pharynx increases the risks of OSA (Shprintzen, 1988). It is therefore important that lateral pharyngeal wall (LPW) function be assessed and appropriate surgical procedures be selected. If LPW function is a concern, some patients with pharyngeal hypotonia may not be good candidates for surgical intervention. However, high, broad pharyngeal flaps have been successfully done on some patients (Argamaso, 1995). Regardless, assessments of these issues and intervention decisions are best made by a cleft palate team.

Roughly 15% of patients with VCF (Shprintzen, 1988) will present at birth with Pierre Robin sequence (cleft palate, retrognathia, and glossoptosis). Obstructive apnea is a potential complication of this sequence. Because the surgery done for VPI has potential to further obstruct the airway, this patient going into the surgery is at even greater risk. At first it may be unclear if the etiology of the upper airway obstruction is due to pharyngeal hypotonia versus glossoptosis found with the isolated Pierre Robin sequence. The site of upper airway obstruction can be investigated via nasopharyngoscopy. The course of treatment will vary (Glander & Cisneros, 1992; Shprintzen et al., 1981). Polysomnography (sleep study) should also be done to rule out central apnea.

Ear Management

A large percentage of children on the pediatric speechlanguage pathologist's caseload present with a history of recurrent ear infections. This usually prompts a referral to an otolaryngologist for medical management. A child with VCF who has yet to be diagnosed may present with a history of recurrent ear infections and upper respiratory infections secondary to a compromised immune system (Weik et al., 1993). To an unsuspecting physician, this profile may make the child a candidate for an adenoidectomy. A missed diagnosis of a submucous or an occult submucous cleft palate can result in VPI following adenoidectomy (Croft, Shprintzen, Daniller, & Lewin, 1978; Finkelstein et al., 1993; Witzel, Rich, Margar-Bacal, & Cox, 1986). Had the speech-language pathologist looked at the whole child and recognized that there was a characteristic facies and a positive family history of cardiac problems, examination for submucous or occult submucous cleft palate or a subtotal adenoidectomy would have been pursued (secondary to suspicion of VCF). Thus, post surgical VPI may have been avoided (Table 1).

Resonance and Voice Management

Hypernasality, denasality, cul de sac resonance, and hoarseness are all resonance and voice characteristics that need to be considered when discussing VPI. Hypernasality is the most common resonance characteristic perceived in patients with VCF. As stated previously, hypernasality is best managed with a surgical and sometimes a prosthetic approach.

Nasal congestion can cause denasality; however, nasal congestion or obstruction in the presence of VPI can result in a cul de sac (nasality in a closed system) resonance quality. The VPI can be elusive in this situation. If the congestion or obstruction can be managed, the VPI is unmasked.

Also, certain laryngeal voice characteristics such as hoarseness, can be caused by VPI due to the use of increased effort levels required by the system air leak and compensatory errors produced at the laryngeal level (i.e., glottal stops). Not only is the hoarseness then a sequela of VPI, but it also masks the hypernasality. This hoarseness, secondary to VPI, is managed differently from the traditional approaches. The VPI as well as the abusive laryngeal patterns need to be managed.

Educational Management

The developmental, psychological, and/or learning profiles of individuals with VCF are variable, but some degree of cognitive impairment and social communication deficits are common concerns. The keen investigator must look at these variables along with other clusters of physical findings to support suspicion of velocardiofacial syndrome. Conversely, identification of the various physical characteristics of the syndrome (i.e., facial features, hypernasality) should lead to further evaluation of a language or learning disability. In some cases, the learning and/or communication deficits are subtle. The child may not meet criteria for exceptional education or speech and language services in the public schools. Unfortunately, many of these students demonstrate functional communication adequate to meet their needs but social communication skills that are deficient (Weik et al., 1993). They also struggle academically. A confirmed medical diagnosis of VCF could allow these children to receive services under the category of Other Health Impaired (OHI) in the public schools.


Shprintzen (1997) has developed a list of over 300 birth defects or malformation syndromes that have communication disorders associated with them, and this list is not exhaustive. Speech-language pathologists have experience in treating various speech, language, oral motor, and voice disorders related to these conditions. Unfortunately, many speech-language pathologists do not appreciate the contribution that they can make in the diagnosis of various genetic syndromes. Velocardiofacial syndrome is a good example of a syndrome that affects multiple systems. The information needed for diagnosis comes from many specialists, but often the first red flags are evident to the speech-language pathologist.

We have attempted to highlight the extreme variability in the expression of this condition. Current evidence shows that the syndrome can be present in individuals who do not demonstrate all the major "classic" features of the condition. In other words, the presence of a structural palate anomaly is not essential to the diagnosis. However, hypernasality, ranging from mild to severe, is a frequent finding. Congenital heart defects are not always present. Similar facial appearances and learning difficulties seem to be the most common features, yet variability in the degree of expression and presentation of deficits also are prevalent in this population. With a better understanding of the spectrum of symptomatology, speech-language pathologists can offer relevant and significant pieces to the diagnostic puzzle. Salient information from the case history review, parent interview, facial and oral peripheral examination, and speech, voice, and language assessments are essential to the differential diagnosis of this syndrome (see Appendix). Appropriate diagnosis leads to more effective treatment, better prognostic information regarding the effects of treatment and its developmental course, and improved total care for these children and their families with regard to both health and planning.

VCF Case Profiles

What follows are profiles on three members of the same family who were diagnosed with velocardiofacial syndrome. Suspicion of the syndrome was raised when the youngest child, E.H., was seen for a preschool speech and language evaluation at the Masters Family Speech and Hearing Center at Children's Hospital of Wisconsin because of his limited expressive vocabulary. Clinical observations of family members, case history information, and clinical evaluation precipitated a referral to the medical geneticist.


E.H., a boy 10 years and 6 months old, was initially referred to the Masters Family Speech and Hearing Center at Children's Hospital of Wisconsin at 23 months of age because of limited expressive speech and language skills (Figures 5a, 5b). Mild motor delays and infant sucking problems were reported. Past medical history was significant for repair of ventral septal defect and insertion of bilateral myringotomy tubes at one year of age. Family history was significant for an older sister with tetralogy of Fallot who also had speech and learning problems. Mother demonstrated mild-moderate hypernasality and the characteristic facies of velocardiofacial syndrome. She had also experienced learning difficulties during her school years.

Results from E.H.'s initial assessment at 23 months indicated mild to moderate receptive and severe expressive speech and language delays. Vocalizations were limited to vowel-like productions and word approximations. Slight, inconsistent hypernasality was reported. Verbal and oral motor imitation skills were poor. Oral examination did not identify any observable structural palatal defects. E.H. presented with a retruded mandible. No other recognizable facial features of the syndrome were evident. Hearing sensitivity was normal on that date.

Although developmental dyspraxia of speech was suspected because of motor planning problems, another communication diagnosis, velopharyngeal inadequacy, could not be ruled out. Given his history of middle ear problems, infant feeding difficulties, retruded mandible, and mother's nasal resonance quality, a submucous or occult submucous cleft palate presented another possibility. Speech therapy and placement in a special education early childhood program were recommended. E.H. also was referred to the cleft palate team at Children's Hospital of Wisconsin for further evaluation. Given the questionable VPI, familial palate and cardiac anomalies, history of learning problems in the family, mother's characteristic facies, and that VCF can have an autosomal dominant inheritance pattern with a 50% recurrence rate (Copenhagen, 1998), a genetics consultation was pursued for E.H., his mother, and his sister to rule out VCF. E.H.'s diagnosis was confirmed at age 2 by the medical geneticist. He has since tested positive for the 22q11 deletion using fluorescence in situ hybridization (FISH).

As his speech skills developed, no hypernasality was documented. Therefore, E.H. never underwent any radiographic or endoscopic evaluations of the velopharyngeal mechanism. Facial appearance is still not classic. Currently, speech skills are described as normal with the exception of interdental distortions of /s/ and /z/. Laryngeal and nasal resonance qualities are within normal limits. Language skills were functional for conversation. Though he is struggling academically, E.H. has not met school criteria that would qualify him for exceptional education services. He continues in regular education with no support. Problems with math are reported.


S.H., E.H.'s older sister, was initially seen by the Cleft Palate Team at Children's Hospital of Wisconsin when she was 8 years old (Figures 6a, 6b). The evaluation was pursued following her and other family members' diagnosis of velocardiofacial syndrome. S.H. has also tested

positive for the chromosome deletion via FISH.

At the time of her initial team evaluation, S.H. was in the second grade, receiving speech therapy at school for articulation problems with /s/ and /z/, language processing weaknesses and mild hypernasality. The /s/ and /z/ distortions may have been a function of reduced lingual tone. She was not enrolled in any other special education support services.

S.H. presents with a history of tetralogy of Fallot; recurrent middle ear and sinus infections; slight, inconsistent hypernasality; articulation delays; and learning disabilities. Videofluoroscopy and nasopharyngoscopy, completed at her cleft palate team evaluation, indicated velopharyngeal insufficiency due to timing problems with the palatal pharyngeal valve. No structural palate anomaly has been identified. She received short term speech therapy at Children's Hospital of Wisconsin to remediate her articulation errors and establish more consistent oral speech productions. This was accomplished in three months. She is currently in high school, receiving support services for learning disabilities, which were diagnosed in fifth grade. Socially, she reportedly gets along with peers and adults, but has mild attending and organizational difficulties. Current physical features include flat midface, broad and prominent nasal root, and slender digits.


L.H. is the mother of E.H. and S.H. (Figure 7). During childhood, she underwent an adenoidectomy and tonsillectomy and insertion of pneumatic ear tubes because of recurrent ear infections. She has demonstrated mild hypernasality since that time.

L.H. was evaluated by the cleft palate team at Children's Hospital of Wisconsin following her diagnosis of VCF. Speech was characterized by moderate hypernasality, reduced intraoral breath pressure, and inaudible nasal air escape. A small gap in the velopharyngeal mechanism was evident on videofluoroscopy and nasopharyngoscopy. An occult submucous cleft palate was identified. Surgery was recommended but not pursued because of lack of insurance coverage. She has also tested positive for the 22q 11 deletion. L.H. was recently diagnosed with a bipolar attention disorder. She has also been receiving psychiatric services.

Each family member brought unique and overlapping pieces to the diagnostic puzzle. E.H.'s history information and his mother's physical findings led to the initial diagnosis of VCF for both. This resulted in further evaluation of E.H.'s siblings. The VCF diagnosis for E.H. and S.H. resulted in appropriate educational planning for the brother and sister. It also helped the mother cope with her psychological and vocational difficulties through psychiatric interventions for her and her daughter. This family's profile underscores the need for thorough case history review, face-to-face interviews and clinical evaluations, and ongoing, periodic monitoring of health, communication, cognitive, and social-emotional status of individuals suspected of having velocardiofacial syndrome.

Author Note

We thank our colleagues Hobie Davies and Wendy Puza for their time and support in completing this paper. We also thank our patients at the Children's Hospital of Wisconsin Masters Family Speech & Hearing Center and Cleft Lip and Palate Center for helping us to investigate and expand our knowledge of velocardiofacial syndrome.

1Occult submucous cleft is sometimes identified on endoscopic evaluation by a flat nasal surface of the velum indicating a hypoplastic musculus uvula in the absence of physical findings of a submucous cleft (Finkelstein et al.. 1993).

2Microform of a cleft is defined as a small slit in the uvula without any other anatomical findings.

3Tetralogy of Fallot is a combination of congenital cardiac defects consisting of pulmonary stenosis, interventricular septal defect, dextroposition of the aorta so that it overrides the interventricular septum and receives venous as well as arterial blood, and right ventricular hypertrophy.


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Gravel, J. S., & Wallace, I. F. (1996). Early otitis media, auditory abilities, and educational risk. American Journal of Speech-Language Pathology, 4(3), 89-94. Haapanen, M-L., & Somer, M. (1993). Velocardiofacial syndrome: Analysis of phoniatric and other clinical findings. Folia Phoniatrica, 45, 239-246.

Lipson, A. H., Yuille, D., Angel, M., Thompson, P. G., Vandervoord, J. G., & Beckenham, E. J. (1991). Velocardiofacial (Shprintzen) syndrome: An important syndrome for the dysmorphologist to recognize. Journal of Medical Genetics, 28, 596-604.

MacKenzie-Stepner, K., Witzel, M. A., Stringer, D. A., Lindsay, W. K., Munro, I. R., & Hughes, H. (1987). Abnormal carotid arteries in the velocardiofacial syndrome: A report of three cases. Plastic Reconstructive Surgery, 80, 347-351. Matzkin, B., Marion, R., Goldberg, R., Shprintzen, R., & Saenger, P. (1993). Variable phenotypes in velocardiofacial syndrome with chromosome deletion. The Journal of Pediatrics, 123, 406410.

Mitnick, R. J., & Shprintzen, R. J. (1996). Velo-cardio-facial syndrome: Pharyngeal MRA and endoscopy. Paper presented at the American Cleft Palate Craniofacial Association annual meeting, San Diego, CA.

Morrow, B., Goldberg, R., Carlson, B. S., Kucherlapati, R., & Shprintzen, R. (1996). Diagnostics for 22ql deletion in patients with velo-cardio-facial syndrome. Paper presented at the American Cleft Palate Craniofacial Association annual meeting, San Diego, CA.

Riski, J. E., Armfield, K., Krause, W., Cohen, S., & Burstein, F. (1997, April). Neurological findings in velocardiofacial syndrome. Poster session presented at the annual meeting of the American Cleft Palate-Craniofacial Association, New Orleans, LA.

Sedlockova, E. (1967). The syndrome of the congenital shortened velum and the dual innervation of the soft palate. Folia Phoniatrica, 19, 44I443.

Shprintzen, R. J. (1988). Pierre Robin, micrognathia, and airway obstruction: The dependence of treatment on accurate diagnosis. The International Anesthesiology Clinic, 26, 179-192.

Shprintzen, R. J. (1997). Genetics, syndromes, and communication. San Diego, CA: Singular Publishers. Shprintzen, R. J., Goldberg, R., Lewin, M. L., Sidoti, E. J., Berkman, M. D., Argamaso, R. V., & Young, D. (1978). A new syndrome involving cleft palate, cardiac anomalies, typical facies, and learning disabilities: Velo-cardio-facial syndrome. Cleft Palate Journal, 15, 56-62. Shprintzen, R. J., Goldberg, R., Young, D., & Wolford, L. (1981). The velo-cardio-facial syndrome: A clinical and genetic analysis. Pediatrics, 67,167-172. Stevens, C., Carey, J. C., & Shigeoka, A. O. (1990). DiGeorge anomaly and velocardiofacial syndrome. Pediatrics, 85, 526-530.

Trost, J. E. ( 1983, November). Differential assessment of structural, neurogenic and functional articulation problems. Short Course presented at the American Speech and Hearing Association Convention, Cincinnati, OH. Velo-Cardio-Facial Syndrome Specialist Fact Sheet. (1997).

Sponsored and available from the Velo-Cardio-Facial Syndrome Institute of Montefiore Medical Center and the Albert Einstein College of Medicine, 3311 Bainbridge Ave., Bronx, NY, 10467.

Weik, L., Carneol, S. O., Marks, S. M., Denny, A. D., & Beste, D. (1993, April). Velocardiofacial syndrome: Reassessment of veto, cardio and facial features. Paper presented at the annual meeting of the American Cleft Palate Craniofacial Association, Pittsburgh, PA.

Witzel, M. A., Rich, R. H., Margar-Bacal, R., & Cox, C.

(1986). Velopharyngeal insufficiency after adenoidectomy: An 8 year review. International Journal of Pediatric Otolaryngology, 11,15-20.

Received May 7,1998

Accepted August 20, 1998

Children's Hospital of Wisconsin, Milwaukee

Contact author: Susan M. Marks, MS, Masters Family Speech & Hearing Center, Children's Hospital of Wisconsin, 9000 W. Wisconsin Ave., P.O. Box 1997, Milwaukee, WI 53201

Copyright American Speech-Language-Hearing Association Feb 1999
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