American Journal of Medical Genetics 43:701-703 (1992)

Interstitial Deletion of 1Oq: Clinical Features and Literature Review Sandra h b o , Jaroelav Cervenka, Arnold London, and Mary Ella M.Pierpont Department of Pediatrics, Variety Club Children’s Hospital (MEEP.)and Hennepin County Medical Center (SL.), and the Department of Om1 Sciences (J.C.),University of Minnesota, Minneapolis; and Aspen Medical Group (A.L.), St. p a l , MiRWSOfXZ

We report on a patient with interstitial deletion of 1Oq and compare her to 8 previously described patients, 2 of whom have chromosomal breakpoints similar to our patient. Minor anomalies including broad forehead, hypertelorism, strabismus, prominent philtrum, and “dyeplastic”pinnae are present in our patient. Psychomotor retardation and hypotonia are universal findings in lOq interstitial deletion. Growth retardation, not present in our patient, is seen in some. These clinical findings are sufficiently distinct to suggest early chromosome studies. Q 1992 Wiley-Lisa, hc.

KEY WORDS: 1Oq interstitial deletion, psychomotor retardation, hypotonia, 1Oq chromosome abnormality INTRODUCTION Deletions of the long arm of chromosome 10 are uncommon cytogenetic abnormalities. Most of the reported cases consist of deletions of the terminal 1Oq bands. A review of the literature uncovered only 8 reports of interstitial deletion of 1Oq. Here, we describe a patient with de novo interstitial deletionof(10)(qll.lq22.1) and compare her phenotypic manifestations with those of the other patients with reported interstitial 1Oq deletions.

CLINICAL REPORT The patient is the second child of healthy, nonconsanguineous parents. An older sib is normal and there is no family history of mental retardation, birth defects, or miscarriages. The pregnancy and delivery were normal and she was born at term with a weight of 3.5 kg, length 52 cm, and head circumference (OFC) 33.5 cm. The neonatal period was unremarkable.

Received for publication May 20,1991; revieion received Odober 11, 1991.

Address reprint requeste to Mary Ella Pierpont, M.D., Ph.D., University of Minnesota, Box 94,420 Delaware Street SE, Minneapolis, MN 55455.

0 1992 Wiley-Lisa, Inc.

She developed numerous episodes of otitis media between 2 and 7 months and ventilation tubes were placed. She also had several episodes of wheezing in association with upper respiratory infections and a t 10 months she was hospitalized with viral pneumonia. A heart murmur was noted at 2 weeks, and confirmed by echocardiography as a small mid-muscular ventricular septa1 defect (VSD). In the first few months, her physical growth was normal but excessive sleeping, passivity, and delay in psychomotor development were evident. At one year she could grasp objects and place them in her mouth. She had no pincer grasp. She could not roll over or sit up unassisted. She had an unusual pattern of crawling by pushing with her feet in prone position. She had some repetitive behaviors such as head shaking and banging her face or leg with one hand. A hearing evaluation including auditory evoked response test was normal at age 12 months. She was tested on the Bayley Scales of Infant Development a t age 19 months. The score indicated a Psychomotor Developmental Index of 97th centile), and interpupillary distance 5.2 cm (97th centile). There was an unusual stellate pigmentation pattern of the iris. The philtrum (1.3 cm, 50th centile) was prominent; she had a bulbous nose, thin bow-shaped upper lip, and thick pinnae which appeared low set. The nipples were widely spaced (13.2 cm, 97th centile). A grade I I W I holosystolic murmur was heard a t the left sternal border. Both thumbs were fingerlike in appearance and there was clinodactyly of the 5th fingers. Dermatoglyphic analysis showed 4 whorls, 5 ulnar loops, and one radial loop. There was 15 degrees of limitation of elbow extension bilaterally and the 2nd and 3rd toes were overlapping bilaterally (Fig. 2). She had generalized hypotonia, and there was some asymmetry of muscle strength with the left side weaker than the right. Peripheral reflexes were normal.

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Loboet al.

Fig. 1. Facial view of the patient at age 24 months.

Fig. 2. Full length view of the patient a t age 24 months.

Laboratory findings included a transient IgG subclass 2 deficiency in the first year of life (8 mg/dl at 8 months rising to 80 mg/dl a t 11months). She had a normal sweat chloride, normal urinary metabolic screen, and normal brain stem auditory evoked responses. At age 12 months, an MRI scan of the brain showed no structural anomalies but an immature myelination pattern. Cytogenetic studies (G-banding)showed an interstitial deletion of 1Oq. The karyotype was 46,XX, del (10)(pteiqll.l::q22.1+qter) in all mitoses (Fig. 3). The parental chromosomes were normal.

or defects are also common findings. Growth retardation and microcephaly are found in 3/9 cases, but not in our patient. Other anomalies found in some of the 9 cases but not listed in Table I include abnormalities of the iris (coloboma or unusual pigmentation) in 3/9 patients, small beaked nose (3/9),bifid uvula (2/9),clinodactyly of the fifth fingers (3/9),increased space between first and second toes (2/9),and abnormalities of the spine such as kyphoscoliosis or lordosis (3/9). The patient reported by Ray et al. [19801had breakpoints which approximately correspond to the breakpoints of the interstitial deletion of our patient. The common findings include psychomotor retardation, hypotonia, normal growth, ear anomalies, broad nasal bridge, hypertelorism, cupid-bow upper lip, sacral dim-

DISCUSSION Our patient has developmental delay, a VSD, minor anomalies, and an interstitial deletion of chromosome (lO)(qll.lq22.1).We have found 8 published reports of interstitial deletions of 1Oq: Ray et al. [1980], Davis et al. [19821, van de Vooren et al. [19841, Shapiro et al. [19851, Glover et al. [19871, Mori et al. [19881, and Rooney et al. [1989]. In the patients reported by Van de Vooren et al. [1984], the mother of the index case had a balanced insertional translocation involving chromosomes 5 and 10. In all the other cases, includingours, the interstitial deletion arose de novo and the parental chromosomes were normal. The clinical findings of the 9 cases including our present case are presented in Table I. While psychomotor retardation and hypotonia are present in all 9 cases, malformation and displacement of ears, telecanthus or hypertelorism, and heart murmurs

Fig. 3. Partial karyotype showing interstitial deletion of chromosome (lO)(qll.lq22.1)in our patient. G-banding analysis.

1Oq Interstitial Deletion

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TABLE I. Manifestations of Reported Patients With 1Oq Interstitial Deletion ~

~~

~

Characteristics

1Oq deletion Growth retardation Psychomotor retardation Hypotonia Plagiocephaly Microcephaly Broad forehead Telcanthushypertelorism Strabismus Lowsetlmalformedears Broadiflat nasal bridge Prominentilong philtrum Cupid-bow upper lip High arched palate Widely spaced nipples Heart defect Sacral dimple Joint limitations

Davis et al. Glover et al. [19821 - [19871

Present case

Ray et al. [19801

qll.lq22.1

qllq21

q21q22

q21.2q22.I

+

+ + +

+ +

+

+ + + + + + +

+

+ + + + +

+ + + +

VSD

Murmur

Murmur

+

+

+ +

+

+

+ + +

+ + + + +

+

Murmur

+

ple, and joint limitations. Patient 6 reported by Shapiro et al. [1985]also has a similar interstitial deletion t o our patient, but additionally has deletion of genetic material from the terminal end of 1Oq which could account for the additional findings of growth retardation and microcephaly in that patient. There are a number of reports of terminal deletions of 1Oq in the literature and these are thought to constitute a syndrome (del10qter).A recent report by Wulfsberg et al. [1989] reviewed the anomalies of 18 cases with del l0qter. Patients with interstitial 1Oq deletions share some of the minor anomalies found in the lOqter group such as hypertelorism, broad or prominent nasal bridge, and malformed ears. Mental retardation and hypotonia are common to all 1Oqdeletions. Growth retardation and microcephaly are frequent in terminal deletions (10qter) but are found only in interstitial deletions with distal breakpoints. Half (9/18) of the patients with terminal deletions had cardiac defects of a variety of types (VSD, tetralogy of Fallot, and others). Three of the 9 patients with interstitial deletions reviewed here had a VSD; of the remaining 6 , 4 had cardiac murmurs. Serious anogenital anomalies, common in terminal deletions of lOq, are not reported in interstitial 1Oq deletions. The chromosome abnormality in our patient was not

ShaDiro et al. i19851 Patient 6

Shaoiro et al. '19851 Patient 7

~ o r et i a]. [19881

Van de Vooren et al. [19841

h o n e y et al. (19891

qll.2q22.1 q26.3qter

+

q22.3q24

q22q24

q24.2q25.3

q25.2q26.1

+ +

+

+ +

+

+ +

+ + + + +

+

+ + + VSD

+ +

+ + + + + + +

+

VSD

+

+

+

+

+ + +

+

+ + +

+ +

+ + + + I

+

Murmur

+

defined until she was one year old. The unremarkable birth and neonatal history, and the normal growth pattern contributed to the delay in diagnosis. However, at age 11months, hypotonia, clear evidence of developmental delay, and unusual facial appearance led to chromosome analysis.

REFERENCES Davis JG, Kardon NB, Selman J E (1982): De novo 1Oq interstitial deletion. Am J Hum Genet 34:122A. Glover G, Gabarron J , Lopez Ballester JA (1987):De novo lOq(q21q22) interstitial deletion. Hum Genet 76:205. Mori MA, Gomez-Sabrido F. Diaz de Bustamante A. Pine1 I. MartinezFrias ML (1988):De novo 10q23 interstitial deletion. J Med Genet 25209-210. Ray M, Hunter AGW, Josifek K (1980):Interstitial deletion of the long arm of chromosome 10. Ann Genet 23:103-104. h o n e y DE, Williams K, Coleman DV, Habel A (1989):A case of interstitial deletion of IOq25.2-q26.1. J Med Genet 2658-60. Shapiro SD, Hansen KL, Pasztor LM, DiLiberti JH, Jorgenson Iw, Young RS, Moore CM (1985):Deletions of the long arm of chromosome 10. Am J Med Genet 20:181-196. Van de Vooren MJ, Planteydt HT, Hagemeijer A, Peters-Slough MF, Timmerman MJ (1984): Familial balanced insertion (5;lO) and monosomy and trisomy (IO)(q24.2-q25.3).Clin Genet 2552-58. Wulfsberg EA, Weaver RP, Cunniff CM, Jones MC, Jones KL (1989): Chromosome lOqter deletion syndrome: A review and report of three new cases. Am J Med Genet 32:364-367.