SOP TRANSACTIONS ON INHERITANCE AND GENETIC ENGINEERING
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SOP TRANSACTIONS ON INHERITANCE AND GENETIC ENGINEERING
A 21 year old patient with a non-lethal 6q
duplication syndrome: A case report
Lynnette Mazur*, Natalie Lodinger, Lisa Wilsford, Susan Soletsky
Shriners Hospital for Children, Houston, Texas
*Corresponding author:
Abstract:
Children born with a duplication of chromosome 6q have a distinct clinical picture that includes microcephaly,
microstomia, webbing of the neck and congenital joint contractures. However, most die in early childhood.
We report a case of a 21 year-old male with the chromosome 6 abnormality and a balanced Robertsonian
translocation of chromosomes 13 and 22.
Keywords:
Chromosome 6 Duplication; Robertsonian Translocation Chromosomes 13 and 22
1. INTRODUCTION
There are more than 50 reported cases of duplication 6q syndrome [1]. However, when the authors performed a
literature search using Pub Med from 1965 to the present, there were no reported cases of a 6q duplication with a
Robertsonian translocation. This report will compare our patient’s clinical findings to other reported patients with an
isolated 6q syndrome.
2. CASE REPORT
Shortly after birth, TP had been presented to the Genetic and Orthopedic Clinics at Shriners Hospitals for Children
in Houston, Texas for evaluation. He was followed until the age of 21 years. He was born of a 29-year-old gravida
3, para 3 white female and a 31-year-old unrelated white male at 36 weeks gestational age. He was delivered via
Caesarean section due to failure to progress.His Apgar scores at 1 and 5 minutes were 8 and 9 respectively. His weight,
length, and fronto-occipital circumference were 1.64 kgs (<5%), 41.5 cm (<3%), and 30cm (5%) respectively. His
physical exam was significant for dysmorphic, triangular facies, hypertelorism, an ovoid mouth with thin lips, a higharched palate, a small chin with a short neck, pectus carinatum, marked hypospadias, thin extremities with upper
extremity contractures, an extra digit of his left hand, tibial torsion and club feet. Magnetic resonance imaging of
the brain showed a small brainstem and an echocardiogram showed an atrial septal defect. His karyotype exhibited
45,XY, dir dup(6) (pter->q27: :23.3->qter),-13,-22,+t(13;22)(p12;p12)mat. The abnormality of chromosome 6
resulted in trisomy of the region 6q23.3->q27. Neither parent had this abnormality, making this rearrangement a de
novo event. Additionally, there was a balanced 13;22 Robertsonian translocation inherited from the mother. Like the
mother, the t(13;22) was dicentric with the centromere of chromosome 13 appearing to be inactivated in some cells.
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SOP TRANSACTIONS ON INHERITANCE AND GENETIC ENGINEERING
Microarray analysis at a later date revealed a copy number gain of chromosome bands 6q24.1q27 of approximately
31.416 Mb in size. He was discharged on day of life 34.
The family history was significant for a maternal half-brother with a stiff club foot deformity, deafness, and an
undescended testicle; his chromosome analysis was normal. A maternal half-sister was clinically and genetically
normal. Several family members had translocation of chromosome 13 and 22. See Figure 1. The chromosome 6
abnormality was not present in any other family members.
Figure 1. Family Tree
During his follow-up visits his height remained below the 5th percentile and his weight varied between the 5th and
25th percentile. Developmentally, he had delayed language and gross motor skills; talking at 2 years, sitting at 18
months, and walking with ankle-foot orthotic devices and a walker at 26 months. He had normal personal social and
fine motor skills. He had numerous surgical procedures; a hernia repair, bilateral posteromedial and posterolateral
releases, a hypospadias repair with bilateral orchiopexy, pressure equalizing tubes, a L4-L5 laminectomy with filum
terminale and tethered cord release, a left foot medial soft tissue release, medial column lengthening, lateral column
shortening, and an os calcis osteotomy. Socially, the patient benefitted from a strong family support system. He
attended public school for several sessions per week and his favorite sport was bowling. His review of systems was
significant for ongoing speech therapy for expressive language delay and physical therapy for generalized weakness,
knee flexion contractures, and an abnormal gait pattern. He had mild myopia and required corrective lenses. Onset of
puberty was within normal range and proceeded normally. At skeletal maturity, the patient had moderate knee flexion
contractures and equinovarus foot deformities but was walking independently without assistive devices.
3. DISCUSSION
Our patient had a duplication of chromosome 6(pter->q27: :q23.3->qter) and a unique balanced Robertsonian
translocation of chromosomes 13 and 22 which may explain his longevity. The longest reported survival of a patient
with an isolated 6q anomaly is 38 years [1]. This patient had predominantly skeletal changes without inner organ
system involvement. The majority of children with a 6q anomaly have a high childhood mortality secondary to inner
organ failure [2–4]. The longest reported survival of a patient with a 6q anomaly and inner organ involvement was
10 years old. This patient had a 6q duplication and a hereditary balanced translocation between chromosomes 6
2
A 21 year old patient with a non-lethal 6q duplication syndrome: A case report
and 17 [2]. A female infant with a duplication of 6q21-6q24 died at 22 days of life. This child had multiple inner
organ involvement including a ventricular septal defect and a patent ductus arteriosus, a patent foramen ovale with
pulmonary failure and severe transient neonatal diabetes mellitus. Additionally, she presented with partial agenesis of
the corpus callosum and bilateral colpocephaly [4]. A male child with a partial duplication of 6q34-qter and a partial
deletion of 13q34-qter had Tetralogy of Fallot, partial aplasia of the cerebellar vermis, and cerebral cortex atrophy.
He had a history of recurrent infections and died at 9 months of age after a cardiac arrest [3].
Our patient had both skeletal and inner organ involvement. His translocation may have improved his prognosis.
We contrast the physical findings of our patient with others having duplication 6q syndrome. See Table 1 [5, 6].
Our patient had a longer duplicated portion of 6q chromosome than other reported cases. Patients with shorter arm
duplications typically have greater skeletal and facial deformities and more severe inner organ involvement [2–4, 7, 8].
Although our patient had organ involvement, they included only a small atrial septal defect and a small brainstem.
And, although he had hypospadias, he did not have renal involvement. Both the longer duplicated portion of the
chromosome and the limited cardiac, neurological, and urological involvement probably contributed to his longevity.
Due to the poor prognosis of patients with a 6q anomaly, at birth, our patient’s parents were advised to forgo any
medical or surgical intervention. They were told that he had limited potential and that he would never ambulate.
However, after his first foot surgery at age 2 years, he began to walk and after further lower extremity procedures,
he became an independent community ambulatory. A recent study on 332 members of parent support groups with
children with other chromosomal anomalies showed that most described their children as happy despite severe
disabilities and generally said that their child enriched the family regardless of how long he or she lived. [9] These
authors concluded that parents may have views, hopes, and expectations that are incongruous with those held by
some of the clinicians they encounter. Healthcare providers should be aware of the experiences of these families and
be open to discussions regarding medical and surgical interventions.
ACKNOWLEDGMENTS
We would like to thank Dr. Jacqueline Hecht for her discussion of the genetics, and Dr. Douglas Barnes for his
discussion of the orthopedics related to this case.
References
[1] A. Smith, A. Jauch, H. Slater, L. Robson, and T. Sandanam, “Syndromal Obesity Due to Paternal Duplication
6(q24.3-q27),” American Journal of Medical Genetics, vol. 84, no. 2, pp. 125–131, 1999.
[2] C. Seel, H.-D. Hager, A. Jauch, G. Tariverdian, and J. Zschocke, “Survival up to age 10 years in a patient with
partial duplication 6q: case report and review of the literature,” Clinical Dysmorphology, vol. 14, no. 1, pp. 51–54,
2005.
[3] M. Erdel, H.-C. Duba, I. Verdorfer, A. Lingenhel, R. Geiger, K.-H. Gutenberger, E. Ludescher, B. Utermann, and
G. Utermann, “Comparative genomic hybridization reveals a partial de novo trisomy 6q23-6qter in an infant with
congenital malformations: delineation of the phenotype,” Human Genetics, vol. 99, no. 5, pp. 596–601, 1997.
[4] N. Fitch, “Partial trisomy 6,” Swiss Soc Neonatalogy, 2005. http://www.neonet.ch.
[5] S. L. Cappon, A. M. Duncan, and M. M. Khalifa, “Interstitial 6q duplication in an adult male without growth
delay or severe mental retardation,” Medical Science Monitor, vol. 6, no. 3, pp. 581–585, 2000.
[6] O. Henegariu, N. A. Heerema, and G. H. Vance, “Mild Duplication 6q Sndrome: A case with partial trisomy
(6)(q23.3q25.3),” American Journal of Medical Genetics, vol. 68, no. 4, pp. 450–454, 1997.
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SOP TRANSACTIONS ON INHERITANCE AND GENETIC ENGINEERING
Table 1. Comparison of physical findings of a duplication of chromosome 6q and the findings in our patient [5, 6].
Key Findings
Duplication 6q
Patient
Short webbed neck
+
+
Microcephaly
+
-
Clinodactyly
+
-
Prominent forehead
+
-
Down-slanting palpebral fissures
+
-
Acrocephaly
+
-
Fingers: Ulnar deviation
+
-
Camptodactyly
+
-
Syndactyly
+
-
Abnormal palmar creases
+
-
Transient Neonatal Diabetes Mellitus
+
-
Joint contractures
+
+
Club foot
+
+
Growth retardation
+
+
Mental retardation
+
+
High arched palate
+
+
Low birth weight
+
+
Flat facies
+
+
Hypertelorism
+
+
Carp shaped mouth
+
+
Micrognathia
+
+
Fingers: Polydactyly
+
+
Kyphoscoliosis(Kyphosis)
+
+
Severe psychomotor retardation
+
+
Low set ears
+
-
Cardiac: murmur/anomaly
+
+
Genitourinary anomaly
+
+
Cerebral anomaly
+
+
Flat/broad nose
+
+
[7] A. S. Kulharya, M. E. Carlin, W. A. Stettler, M. Huslig, M. K. Kukolich, and J. Garcia-Heras, “Prenatal diagnosis
of a de novo trisomy 6q22.2-¿6qter and monosomy 1pter-¿1p36.3. Case report with a 2-year follow-up and a
brief review of other prenatal cases of partial trisomy 6q,” Clinical Genetics, vol. 51, no. 2, pp. 115–117, 1997.
[8] R.-D. WEGNER, E. Schröck, M. Obladen, R. Becker, M. Stumm, and K. Sperling, “Partial Trisomy/Monosomy
6q in Fetal Cells and CVS Long-term Culture Not Present in CVS Short-term Culture,” Prenatal Diagnosis,
vol. 16, no. 8, pp. 741–748, 1996.
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