Mutchinick Syndrome in a Japanese Girl

Hidefumi Tonoki,1,2* Tetsuo Hattori,3 Hisako Kamoshida,3 Yachio Ohta,3 and Norio Niikawa4

1Division of Cell Biology, Cancer Institute, Hokkaido University School of Medicine, Sapporo, Japan2Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan3Tenshi Hospital, Sapporo, Japan4Department of Human Genetics, Nagasaki University School of Medicine, Nagasaki, Japan

We report on a 7-year-old Japanese girl withMutchinick syndrome, a rare congenitalmalformation syndrome described in a pairof Argentinean sisters and a pair of Germanbrothers; both originating from the samegeographic region in the former East Prus-sia. The girl we describe had most of theclinical manifestations of the syndrome, in-cluding growth and developmental retarda-tion, and craniofacial anomalies with micro-cephaly, hypertelorism, a broad straightnose, low-set malformed ears, and a wide,tented mouth. She also had the followinghitherto undescribed manifestations: ven-tricular septal defect, palmoplantar hyper-keratosis, bilateral partial soft-tissue syn-dactyly of second and third toes, and mega-loureters. The occurrence of the syndromein a Japanese girl indicates that the syn-drome is not restricted to the descendantsof individuals from a confined region innortheastern Europe. Am. J. Med. Genet. 83:96–99, 1999. © 1999 Wiley-Liss, Inc.

KEY WORDS: Mutchinick syndrome; con-genital malformation syn-drome; megaloureters; auto-somal recessive inheritance;facial anomalies

INTRODUCTION

Mutchinick in 1972 described two Argentinean sis-ters with a multiple congenital anomaly syndromecharacterized by growth retardation, peculiar facial ap-pearance with hypertelorism and broad straight nose,mental retardation, speech disorder, and multiple or-gan malformations [Mutchinick, 1972]. More recently,Doerfler et al. [1997] reported on two German brothers

with the syndrome. Autosomal recessive inheritance ofthe disorder was suggested in view of its occurrence intwo pairs of sibs, and because the parents of the sistersreported by Mutchinick [1972] were double-cousinsonce removed. Because the two families originatedfrom small towns in the same geographical region ofthe former Ostpreussen (East Prussia), the findingsuggested a founder effect. We here report on a Japa-nese girl with the syndrome.

CLINICAL REPORT

A Japanese girl, C.M., was born at 39 weeks of ges-tation to a 21-year-old, P1 mother and a 33-year-oldfather, both healthy and nonconsanguineous. Intra-uterine growth retardation (IUGR) and bilateral mega-loureters were noted at 36 weeks of gestation. Apgarscore was 7 at 1 min. Her birth weight was 2,270 g(−2.3 SD), length 48 cm (−0.7 SD), and OFC 30.6 cm(−1.8 SD), and she was found to have a ventricularseptal defect (VSD), megaloureter, and dilated renalpelvis. She had feeding difficulties during early in-fancy, and suffered from recurrent urinary tract infec-tions and chronic constipation in infancy and earlychildhood. She lifted her head at age 6 months, turnedover at 10 months, sat at 14 months, walked alone at 34/12 years, and spoke meaningful words at age 3 6/12years.

When referred to us at age 3 7/12 years, she weighed9 kg (−3.5 SD), measured 87 cm (−2.4 SD), and OFCwas 44 cm (−3.5 SD). She had microbrachycephaly, alow posterior hair-line, a broad webbed neck, low-pitched hoarse voice, a characteristic facial appearanceincluding narrow forehead, bushy and arched eye-brows, hypertelorism, small palpebral fissures withptosis, downward slant of the palpebral fissures, longcurly eyelashes, a broad straight nose with prominentnasal bridge, low-set, posteriorly rotated small ears, athin upper lip, a wide, tented mouth, a high-archedpalate, prognathism, and pointed chin (Fig. 1), limitedextension of metacarpophalangeal joints of bilateralsecond to fifth fingers, bilateral partial cutaneous syn-dactyly between second and third toes, and spastic gait.Dental malocclusion was not evident. Neurocutaneouslesions included generalized dry and hypopigmentedskin and hair, photophobia, mottled appearance of theocular fundi, and bilateral palmoplantar hyperkerato-

*Correspondence to: Hidefumi Tonoki, M.D., Ph.D., Division ofCell Biology, Cancer Institute, Hokkaido University School ofMedicine, N-15, W-7, Sapporo 060-8638, Japan. E-mail:tonoyan@med.hokudai.ac.jp

Received 3 September 1998; Accepted 1 December 1998

American Journal of Medical Genetics 83:96–99 (1999)

© 1999 Wiley-Liss, Inc.

sis. The irides were dark brown. Dermatoglyphic ex-amination was not possible because of hyperkeratosis.Bone age was normal. Ultrasonography showed bilat-eral megaloureter and dilatation of the renal pelvis.Voiding cystography demonstrated absent vesicoure-teral reflux. Brain computed tomographic scan, electro-

enchephalography, auditory brain stem response, andelectrocardiography were all normal. Chromosomeswere 46,XX.

When last seen at age 7 years, she weighed 13 kg(−2.5 SD), measured 108 cm (−1.7 SD), and OFC was 45cm (−5.5 SD). She attended a special class of school.

Fig. 1. Photographs of the patient at age 3 7/12 years (A) and 7 years (B–E).

Mutchinick Syndrome 97

She spoke a lot but totteringly. Her intelligence quo-tient (IQ) was estimated at 42.

DISCUSSION

The girl we described had most of the clinical mani-festations of the Mutchinick syndrome. Her clinicalmanifestations are compared with those of the sistersreported by Mutchinick [1972] and the brothers de-scribed by Doerfler et al. [1997] in Table I. The clinicalmanifestations common to all these five patients weredelayed development, speech disturbance, microcepha-ly, pale-colored hairs, downward slant of the palpebralfissures, broad straight nose, low-set and malformedears, wide tented mouth, thin upper lip, high-archedpalate, and prognathism. These manifestations are di-agnostic of the Mutchinick syndrome. Common to ourpatient and the sisters reported by Mutchinick [1972]were hypertelorism, blepharophimosis, long curly eye-lashes, photophobia, and white skin, while prenatalgrowth retardation (IUGR) was present in our patient

and the brothers reported by Doerfler et al. [1997]. Themanifestations seen in both or either of the sib pairsbut absent in our patient were hydrocephalus, light-colored iridis, large protruding ears, dental malocclu-sion, and genu valgum. Present in the girl we describedbut not reported previously were VSD, megaloureter,dry skin, palmoplantar hyperkeratosis, and cutaneoussyndactyly of second and third toes. Other inconstantmanifestations include failure to thrive, neonatal feed-ing difficulty, blepharophimosis, ptosis, chest deformi-ty, and spastic insecure gait. Baraitser-Winter syn-drome [Baraitser and Winter, 1988] has some clinicalmanifestations in common with those in the girl wehave described, including mental retardation, shortstature, microcephaly, hypertelorism, ptosis, and lowhair-line. However, the presence of characteristic facialanomalies and the absence of iris coloboma in our pa-tient render the diagnosis unlikely. Rubinstein-Taybisyndrome is another candidate for differential diagno-sis because craniofacial appearance is similar, includ-ing microcephaly, arched eyebrows, prominent nose,

TABLE I. Comparison of the Clinical Manifestations in Five Patients With Mutchinick Syndrome

This report(C.M.)

Mutchinick [1972] Doerfler et al. [1997]

IV-1 IV-3 Mat.K. M.K.

Sex F F F M MPhysical and mental development

Prenatal growth retardation + NRa − + +Failure to thrive + + + − +Neonatal feeding difficulty + + − − NRShort stature + + + − +Delayed milestone + + + + +Speech disturbance + + + + +IQ 48 42 NR 75–95 NR

Craniofacial abnormalitiesMicrocephaly + + + + +Hydrocephalus − − − + +Brachycephaly + + + − −Pale-colored hair + + + + +Hypertelorism + + + − −Blepharophimosis + + − − −Ptosis + + − + +Downward slant of palpebral fissures + + + + +Long curly eyelashes + + + − −Ligh colored-iris − + + + +Broad straight nose + + + + +Low-set ears + + + + +Large protruding ears − + + + +Wide, tented mouth + + + + +Thin upper lip + + + + +High-arched palate + + + + +Dental malocclusion − + − + +Prognathism + + + + +

Internal organ abnormalitiesVentricular septal defect + − − − −Renal involvement + + + − −Megaloureter + − − − −

Other abnormalitiesWhite skin + + + NR NRPhotophobia + + + NR NRPalmoplantar hyperkeratosis + − − − −Cutaneous syndactyly of toes + − − − −Spastic insecure gate + + + − +Genu valgum, pes valgus − − + + −Chest deformity + + − − +

aNR, not recorded.

98 Tonoki et al.

and pointed chin. However, the absence of broadthumbs and toes in our patient rules it out.

It was noteworthy that both pairs of sibs with theMutchinick syndrome previously reported were de-scended from families who used to live in a restrictedregion of the former East Prussia [Mutchinick, 1972;Doerfler et al., 1997]. The occurrence of the syndromein a Japanese girl indicates that the syndrome is notrestricted to the individuals originating from theformer East Prussia.

REFERENCES

Baraitser M, Winter RM. 1988. Iris coloboma, ptosis, hypertelorism, andmental retardation: A new syndrome. J Med Genet 25:41–43.

Doerfler W, Wieczorek D, Gillessen-Kaesbach G, Albrecht B, Passarge E.1997. Three brothers with mental and physical retardation, hydroceph-alus, microcephaly, internal malformations, speech disorder, and facialanomalies: Mutchinick syndrome. Am J Med Genet 73:210–216.

Mutchinick O. 1972. A syndrome of mental and physical retardation,speech disorders, and peculiar facies in two sisters. J Med Genet 9:60–63.

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