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Logo of archdischArchives of Disease in ChildhoodVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Arch Dis Child. 2007 April; 92(Suppl1): A63–A64.
PMCID: PMC2066116


Clinical genetics

G/WEDS/GEN1 A case of del(4)(q33): presentation of a girl with an encephalocele

A. Vaglio1, M. Larrandaburu1, B. Mechoso1, A. Quadrelli1, R. Quadrelli1, H. Zhu2, Y. Fan2, T. Huang3, E. Strehle4. 1Hospital Italiano, Montevideo, Uruguay; 2Mailman Center for Child Development, Miami, USA; 3University of California, Irvine, USA; 4Centre for Life, Newcastle upon Tyne, UK

We present clinical and developmental data on a girl with a de novo terminal deletion of the long arm of chromosome 4, del(4)(q33). The patient was evaluated at birth and followed up until 5 years of age. She showed facial and digital dysmorphism, a complex congenital heart defect, a large occipital encephalocele and postnatal growth deficiency. Her neuropsychomotor milestones were delayed and she developed learning difficulties. Apart from standard Giemsa banding, a molecular genetic analysis was performed using a comparative genomic hybridization (CGH) array. This revealed a terminal deletion at the band 4q32.3, which is directly adjacent to 4q33. The clinical findings in our patient differ from those described previously in patients with del(4)(q33) and del(4)(q32), respectively. In particular, the prominent occipital encephalocele has not been observed before in a terminal 4q deletion.

G/WEDS/GEN2 Rothmund–Thomson syndrome: a rare multisystemic disorder

V. Rao, S. Rambatla. WalsalltPCT, Walsall, UK

BackgroundRothmund–Thomson syndrome is an extremely rare inherited multisystem disorder, characterised by distinctive abnormal skin, hair defects, juvenile cataracts, skeletal abnormalities, short stature, hypogonadism and risk of cancers

Case PresentationUA is the third child of a Pakistani couple. She was dysmorphic, small for dates, had very pale skin for her ethnicity. She had corrective surgery for anal atresia with recto‐vaginal fistula, and for hypoplastic thumbs. She remained under the care of the community child health service for her learning difficulty and short stature. At age 15 she remained small, had delayed puberty, alopecia and myopia. Her face was wizened, with a large bulbous nose. Her skin was keratotic in places.

InvestigationsKaryrotype and thyroid function were normal. Tests for delayed puberty confirmed primary ovarian failure, tiny prepubertal uterus, with only a small right ovary. Bone age was only marginally delayed.

Family HistoryMother had a bad obstetric history. There was multiple consanguinity with parents being second cousins and grandparents first cousins. Her first cousin 25, a girl in Pakistan is reported to have similar physical features to UA, but had not much of a learning difficulty.

DiagnosisDyskeratosis congenita, and TPR syndromes were considered and ruled out. Our case appears to be autosomal recessively inherited, very likely a variant of Rothmund–Thomson syndrome. Further genetic studies are in progress.

G/WEDS/GEN3 Developing personal health records for children with common genetic disorders

P. Griffiths1, R. Abbott2, J. Clayton‐Smith1, G. Evans1, S. Harrison1, E. Howard1, S. Huson1, M. Kenney1, K. Metcalfe1, S. Collitt1, B. Kerr1. 1Central Manchester and Manchester Children's University Hospitals NHS Trust, Manchester, UK; 2Neurofibromatosis Association, Kingston Upon Thames, Surrey, UK

Personal health records (PHRs) are client held records. There are numerous examples of these in general medicine, but relatively few have been developed for genetic conditions and fewer still designed specifically for children. Their primary aim is to empower individuals and their families, giving them more information about and ultimately more control over their health. They also benefit the teams of healthcare professionals managing the care of these children, especially where the conditions are complicated and variable. They do this in several ways including: facilitating interspeciality communication, providing readily accessible summaries of the patient's history and current condition, informing and educating non‐genetic healthcare professionals, and they are also a useful tool for the collection of audit information.

Our project involves developing records for a range of common genetic conditions, including neurofibromatosis type 1 (Nf1), achondroplasia, and 22q11 deletion syndrome. These are relatively common, autosomal genetic conditions which are variable and unpredictable and affected children carry a significant risk of developing serious complications. Children therefore need regular reviews and targeted screening at specific ages, and may be under the care of several specialists at community, district and tertiary levels.

The records have been developed by consensus group, comprising consultant geneticists, and genetic counsellors. In each case, advice and input from the relevant patient support organisation has been sought. The records are A5 and can be filed at the back of the child's existing Personal Child Health Record. They typically contain: contact details, targeted information pages, space to record clinical details, pointers to further sources of information and support, as well as a section for families to make their own notes.

The Nf1 record has been piloted locally and pilots for the 22q11 and achondroplasia will start in January 2007. The usefulness of the records will be evaluated by questionnaire surveys of families and professionals using the records. The results from the Nf1 pilot are currently being analysed but initial feedback from both the patients and professionals is overwhelmingly positive. In the future, we hope that PHRs for children with genetic disorders will be widely available across all healthcare sectors and will be accepted as the gold standard in paediatric care.

G/WEDS/GEN4 Prevalence and genetic profile of mucopolysaccharidosis type 1 in the Irish population

A. Murphy, E. Treacy, A. O'Meara, S. Lynch. The Children's University Hospital, Temple Street, Dublin, Ireland

AimsTo document prevalence rates of the three clinical phenotypes of mucopolysaccharidosis Type 1 Hurler (severe), Hurler–Scheie (intermediate) and Scheie (mild) in the Republic of Ireland using population data from the Government of Ireland census in April 2002.

MethodsDatabase and chart review of all live patients with MPS1 attending two specialised centres in 2002. Patient genotypes, iduronidase activity, ethnic background, province of origin, age at diagnosis and presenting clinical features were recorded.

ResultsThirty patients were alive. One patient had Scheie, four Hurler–Scheie and 25 had Hurler syndrome, giving an overall prevalence of 7.66 per million for MPS 1 in Ireland. 19/25 (76%) patients from the Hurler group (age range 4 months to 14 years 10 months) were members of the “Irish traveller” community. All had the same W402X homozygous mutation. There are 23 681 travellers in Ireland. 10 001 are under 15 years of age giving a prevalence of 19 per 10 001 or 1 in 526 for Hurler's syndrome among Irish traveller children. The patient with the mild phenotype and all for patients with the intermediate phenotype hail from the same province. 3/4 carry the same heterozygous W402X/P496L mutation.

ConclusionA prevalence 1/526 for hurler syndrome among “traveller” children is the highest recorded for this condition worldwide and equates with a carrier frequency of 1/11. Given the catastrophic morbidity of delayed treatment and availability of effective treatment (enzyme replacement therapy by iv infusion and stem cell transplant), we recommend screening all babies from this population for Hurler syndrome.

G/WEDS/GEN5 Genetic mimic of congenital infection: a new case of Aicardi–Goutieres syndrome due to biallelic mutations in TREX1

E. Archary1, G. P. Sinha1, Y. Crow2. 1Walsall Manor Hospital, Walsall, West Midlands, UK; 2Bradford Royal Infirmary and Leeds Institute of Molecular Medicine, Leeds, UK

IntroductionIntra‐uterine growth restriction, microcephaly, hepatosplenomegaly, thrombocytopenia and intracranial calcification are characteristic of intra‐uterine infection by agents such as TORCH and HIV. In 1984, Aicardi and Goutieres described similar findings associated with a CSF lymphocytosis and inherited as an autosomal recessive trait. Aicardi‐Goutieres syndrome (AGS) is genetically heterogeneous and recently four genes have been identified, mutations in any of which may give rise to this Mendelian mimic of congenital infection.

Case ReportWe report a male infant born to non‐consanguineous Afro‐Caribbean parents. The pregnancy was uneventful and baby was born by normal vaginal delivery at 37 weeks gestation. He was severely growth retarded with a birth weight of 1.76 kg and head circumference of 29 cm, both <0.4th centile. He had a generalised petechial rash, purpuric spots and hepatosplenomegaly. Further evaluation revealed a left partial facial palsy, left 6th nerve palsy and severe sensory neural deafness. The initial blood count demonstrated a pancytopaenia and he required multiple blood and platelet transfusions. He also had elevated liver enzymes and a coagulopathy but liver ultrasound and dopplers were normal. Cranial MRI scan revealed periventricular calcification and ventriculomegaly. Congenital infection and disorders of mitochondrial function were excluded. Bone marrow biopsy showed dysplastic changes but no neoplasia. Serum and CSF α‐interferon levels were raised suggesting a diagnosis of AGS. This was later confirmed by demonstrating that the patient was compound heterozygous for two TREX1 mutations, c.500delG and c.365T>C (p.V122A). The patient subsequently developed eczema, multiple seizures and respiratory failure necessitating intensive care. At 6 months of age his thrombocytopaenia shows improvement with a moderate anaemia. His development remains severely globally impaired.

ConclusionOur case highlights the remarkable phenotypic overlap of Aicardi–Goutieres syndrome with congenital infection. Recognition of this autosomal recessive disease is necessary in order to avoid counselling of a falsely low risk of recurrence.

Articles from Archives of Disease in Childhood are provided here courtesy of BMJ Publishing Group