Rhabdomyomatous hamartomata of the pharyngeal region with bilateral microtia and aural atresia: a new association?

BACKGROUND: Bilateral microtia with aural atresia is rare. Rhabdomyomatous hamartomata containing salivary tissue, situated bilaterally and symmetrically simulating the palatine (faucial) tonsils, has apparently not been reported. We present the combination of these findings in two unrelated patients. CASES: In the first case, the patient was exposed prenatally to 13-cis-retinoic acid (isotretinoin) and has typical features of this exposure, including bilateral microtia with aural atresia and bilateral 7th nerve palsies. Due to symptoms of obstructive sleep apnea, patient 1 had a "tonsillectomy" and adenoidectomy. Histopathologic studies demonstrated rhabdomyomatous hamartomata containing salivary and striated muscle tissue in place of the palatine tonsils. In the second case, the patient had been prenatally exposed to alcohol, cocaine, and marijuana. He has been noted to have developmental delay and behavioral issues in addition to bilateral microtia with aural atresia. "Tonsillectomy" and adenoidectomy were performed to alleviate chronic upper respiratory infections and snoring. Again, histopathologic studies of the tissue submitted as "tonsil" demonstrated rhabdomyomatous hamartomata containing salivary and muscle tissue. Although an extended banded karyotype and subtelomere panel were normal, a genetic etiology for the second patient's features cannot be excluded. CONCLUSIONS: We hypothesize that the findings of bilateral microtia with aural atresia and rhabdomyomatous hamartomata containing salivary and muscle tissue in the area of the palatine tonsils may represent a newly recognized association, which may have a teratogenic and/or genetic etiology.

Clinical features and management issues in Mowat-Wilson syndrome.

Mowat-Wilson syndrome (MWS) is a relatively newly described multiple congenital anomaly/mental retardation syndrome. Haploinsufficiency of a gene termed ZFHX1B (also known as SIP1) on chromosome 2 is responsible for this condition, and clinical genetic testing for MWS recently became available. The majority of reports in the literature originate from Northern Europe and Australia. Here we report our clinical experience with 12 patients diagnosed with MWS within a 2-year period of time in the United States, with particular emphasis on clinical characteristics and management strategies. Individuals with this condition have characteristic facial features, including microcephaly, hypertelorism, medially flared and broad eyebrows, prominent columella, pointed chin, and uplifted earlobes, which typically prompt the clinician to consider the diagnosis. Medical issues in our cohort of patients included seizures (75%) with no predeliction for any particular seizure type; agenesis of the corpus callosum (60% of our patients studied); congenital heart defects (75%), particularly involving the pulmonary arteries and/or valves; hypospadias (55% of males); severely impaired or absent speech (100% of individuals over 1 year of age) with relatively spared receptive language; and Hirschsprung disease (50%) or chronic constipation (25%). The incidence of MWS is unknown, but based on the number of patients identified in a short period of time within the US, it is likely greatly under recognized. MWS should be considered in any individual with severely impaired or absent speech, especially in the presence of seizures and anomalies involving the pulmonary arteries (particularly pulmonary artery sling) or pulmonary valves.

Turner syndrome: an update and review for the primary pediatrician.

Turner syndrome (TS) is among the most common of the sex chromosomal aneuploidies. It results from the absence of one sex chromosome (or part of an X chromosome) in a female, leaving only one X chromosome present in the cell. Primary care physicians should be able to recognize the presenting signs and symptoms of TS, and once the diagnosis is confirmed by a chromosome analysis, they should be able to serve as a valuable source of support for the patient and her family and understand the most current treatments available.

X-linked fetal cardiomyopathy caused by a novel mutation in the TAZ gene.

OBJECTIVES: Mutations in the tafazzin (TAZ) gene at chromosomal locus Xq28 are responsible for Barth syndrome (BTHS), X-linked endocardial fibroelastosis (EFE), X-linked fatal infantile dilated cardiomyopathy (CMD3A), and familial isolated noncompaction of left ventricular myocardium (INVM). This evaluation was performed to determine if a known familial TAZ gene mutation might present with abnormal fetal cardiac pathology findings as early as the second trimester of pregnancy. METHODS: Prenatal diagnosis revealed that a male fetus was positive for a known familial arg94his TAZ gene mutation. An elective termination with subsequent fetal pathology examination was performed at 18 weeks' gestation. RESULTS: Fetal examination revealed cardiomegaly, EFE, and subendocardial vacuolization of the myocytes. CONCLUSION: Characteristic cardiac pathology findings of a TAZ gene mutation are seen in a fetus at 18 weeks' gestation. To our knowledge, this case provides the earliest fetal pathologic description of a TAZ cardiomyopathy.

Mosaic trisomy 4: Long-term outcome on the first reported liveborn.

In a previous report, we described the first liveborn with trisomy 4 mosaicism [Marion et al. (1990) Am J Med Genet 37:362-365]. To our knowledge, since our original report, there have been only four additional reports of a prenatal diagnosis of mosaic trisomy 4 resulting in a liveborn child [Hsu et al. (1997) Prenat Diag 17:201-242; Kuchinka et al. (2001) Prenat Diag 21:36-39; Wieczorek et al. (2003) Prenat Diag 23:128-133; Zaslav et al. (2000) Am J Med Genet 95:381-384]. Three of the more recent reports lacked confirmation of the mosaicism in tissue samples collected from the child after delivery, and likely represent cases of confined placental mosaicism. We recently examined our original patient, N.J., in an effort to provide long-term follow-up. N.J. is currently 14-years-old, and is enrolled in both special education and mainstream eighth grade classes at a local public middle school. Although she generally scores below average on standardized intellectual tests, her verbal skills and social interactions are more age appropriate. Our initial report described abnormalities of N.J.'s right hand and right ear, for which several reconstructive surgeries have been performed. A current medical concern is her entrance into puberty, as menarche has not yet occurred, and asymmetrical breast development is present. Overall, N.J. has developed into a generally healthy adolescent with low-normal intellect. This report demonstrates the importance of long-term follow-up in providing accurate counseling for rare chromosomal disorders.