A rare case of split hand/foot malformation with sensorineural hearing loss and Mondini dysplasia

Gezdirici, Alpera; Yenigun, Alperb; Koparir, Erkana; Yosunkaya, Elifa; Ulucan, Hakana; Seven, Mehmeta; Yuksel, Adnanc; Ozen, Mustafaa,c

doi: 10.1097/MCD.0b013e32835b8e6e
Short Case Reports

aDepartment of Medical Genetics, Cerrahpasa Medical School, Istanbul University

bDepartment of Ear, Nose and Throat Diseases

cPediatrics and Medical Genetics, Bezmialem Vakif University, Istanbul, Turkey

Correspondence to Mustafa Ozen, MD, PhD, Department of Medical Genetics, Cerrahpasa Medical School, Istanbul University, Cerrahpasa Tip Fakultesi, Tibbi Genetik AD, Fatih, 34098 Istanbul, Turkey Tel: +90 212 414 3000/21304; fax: +90 212 414 3184; e-mail: mozen@bcm.edu

Received March 11, 2012

Accepted October 16, 2012

Article Outline
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List of key features

Facial asymmetry

Broad and prominent nasal root

Irregular placement of teeth

High-arched palate

Cutaneous syndactyly



Split foot anomaly

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Split hand and foot malformations (SHFMs) are found in a large heterogeneous group of disorders, resulting from maldevelopment of the central rays of the limb buds, and are reported to occur in one in 10 000 to 90 000 live births. They can occur as an isolated defect or as a part of a variety of syndromes (Ignatius et al., 1996). Syndromic and isolated SHFM are inherited mostly in an autosomal dominant manner, although X-linked and autosomal recessive forms have been reported (Tackels-Horne et al., 2001). SHFM is associated with six different loci. These include SHFM1 on chromosome 7q21, SHFM2 on Xq26, SHFM3 as a result of 10q24 duplication, SHFM4 as a result of a mutation in P63 located on chromosome 3q27, SHFM5 on chromosome 2q31, and SHFM6 as a result of a mutation in the WNT10B on chromosome 12q13 (OMIM ID: 183600). SHFM1 is accompanied by hearing loss in ∼35% of the patients (Elliott and Evans, 2006). SHFM1 along with deafness has been identified as a distinct clinical disorder (SHFM1D; OMIM ID: 220600). The first case of SHFM1D was reported in 1963 by Wildervanck and colleagues, and linkage studies carried out in two families identified the disease locus as chromosome 7q21 (Tackels-Horne et al., 2001). No ectodermal abnormalities are associated with SHFM1D and karyotypes have been found to be mostly normal (Ignatius et al., 1996).

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Clinical report

The index patient presented to us when she was 37 years old. Informed consent for investigations and publication was obtained from the patient in a format approved by the Ethical Committee of Cerrahpasa Medical School. The family history did not indicate any significant information. Our patient is the third child of healthy, unrelated Turkish parents. Natal and prenatal history is unknown. There is no family history of limb malformations, mental retardation, nor hearing loss. At birth, the patient was found to have malformations in all four limbs. Neurodevelopmental progress was age appropriate. When she was 1 year old, her family recognized that she had hearing problems but they did not seek any professional help. In adult life, on clinical examination, she had facial asymmetry, and a broad and a prominent nasal root (Fig. 1a). Oral examination indicated irregular placement of teeth and a high-arched palate (Fig. 1b). There was cutaneous syndactyly between the third and the fourth fingers in the right hand and ectrodactyly in the left hand and camptodactyly in the second finger (Fig. 1c and d). Bilateral split foot anomaly was observed in the lower limbs (Fig. 1e and f). These features were confirmed by radiographs. She had one 1×2 cm café au lait patch on the lower right abdominal quadrant. The patient’s other systems including respiratory, circulation, and genital system examinations were normal. Biochemistry tests indicated a low thyroid-stimulating hormone level (0.009 mIU/l, normal range: 0.4–4.2 mIU/l), normal free T4 level, and normal free T3 levels. The antithyroglobulin antibody level was elevated, suggesting Hashimoto’s thyroiditis, and the patient was referred to the department of endocrinology for follow-up. Audiological examination was carried out; the appearance of the tympanic membrane was normal on both sides; the middle ear pressures were recorded as a normal on tympanograms, but the pure tone audiogram showed an average of 75 dB sensorineural hearing loss in both ears. 2-mm thick, high-resolution, computer-based temporal bone tomography of axial, coronal, and sagittal planes was performed. This indicated that both cochleas were broader than normal (Fig. 2a); cochlea turns were not observed clearly and both vestibulums were wider than usual (Fig. 2b and c). Cranial MRI and echocardiographic studies showed no pathology. Chromosomal analysis indicated a 46,XX, normal female karyotype at a 450 band level.

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SHFM1 with sensorineural hearing loss (MIM 220600) is a rare SHFM variant. In 1971, Mondini described Mondini dysplasia of the cochlea as having one and half turns, instead of two and three-fourth turns (Phelps, 1994). This deformity is usually unilateral, but bilateral cases have also been reported (Ohlms et al., 1990). In a 7-week embryo, the cochlea has only one and a half turns and any problem in maturation at this stage causes Mondini deformity. Development of the modiolus and bone spiral lamina are also hypoplastic and the cochlear duct is often dilated and shorter. Atrophy is observed of the striae vascularis. The cortical organ is mostly absent and the spiral ganglion cell number is significantly reduced. Endolymphatic duct, and vestibule and semicircular canals might also be enlarged. In addition, there is an anomaly in many patients of the stapes structure (Ohlms et al., 1990). A patient with Mondini dysplasia may present with unilateral or bilateral hearing loss of various levels, cerebrospinal fluid otorrhea, rhinorrhea, or recurrent episodes of meningitis. We suggest that children with congenital hearing loss and/or meningitis history should be evaluated for inner ear malformations. It may also be found with Klippel–Feil syndrome, Pendred syndrome, or Di-George syndrome or as a result of certain teratogenic drugs. Recently, SHFM1D was found with Mondini dysplasia in a boy with a de-novo deletion of chromosome 7q21.1–q21.3 (Wieland et al., 2004). This microdeletion included the SHFM1 candidate genes DLX5, DLX6, and DSS1. In mice, all these putative candidate genes are apparently involved in limb formation, as well as in association with inner ear and severe craniofacial defects. However, Bernardini et al. (2008) reported a complex rearrangement of chromosomes 7q21.13–q22.1 confirming the ectrodactyly-deafness locus, but suggesting new candidate genes. Our patient also had Hashimoto thyroiditis, but this may be coincidental to her limb and hearing problems. There are no reported point mutations in DLX5, DLX6, nor DSS1 in SHFM1D patients to date. Our case adds to the suggestion that Mondini dysplasia is a feature of SHFM1D and that imaging studies are indicated in SHFM1D patients.

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Conflicts of interest

There are no conflicts of interest.

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