Rare Chromosomal Disorder Research Articles

Developmental Delay and Rehabilitation in an Infant with Partial Trisomy 1q32.1 to 1q44: A Case Report

Partial trisomy 1q is a rare chromosomal disorder characterized by ventriculomegaly with craniofacial, renal, cardiac, and finger and toe anomalies. Most reported cases of partial trisomy1q have involved stillborn or premature deaths due to cardiac or liver failure. This case report describes an 18-month-old patient with partial duplication of the 1q32-44 segments and consequent developmental delays who exhibited improvement in developmental status with rehabilitation. Prenatal ultrasonography and magnetic resonance imaging of the mother revealed ventriculomegaly and atrophic changes in the left cerebral hemisphere of the fetus. The infant was born with micrognathia, microphthalmia, macrocephaly, low-set ears, polydactyly, and long feet at 37+5 weeks of gestation. A chromosomal study revealed an abnormal male karyotype of 46,XY,rec(1)dup(1)(q32.1q44)inv(1)(p36.3q32.1)pat. In this rare case of a patient with partial trisomy, we observed improvement in developmental delays following treatment using appropriate rehabilitation techniques. Further research is required to help validate the findings of this case study and establish a standardized rehabilitation technique that can be subsequently applied to such cases.

EP093: De novo interstitial deletion of chromosome 7p22.1p21.2: A case report

Partial monosomy of the short arm (p) of chromosome 7 is a rare chromosomal disorder associated with a variable phenotype, depending on the size and location of the deleted region. When the deletion involves the interstitial deletion of 7p22.1p21.2 region, literature review describes phenotypic features that include craniosynostosis, microcephaly, ocular hypotelorism or hypertelorism, downslanting palpebral fissures, epicanthal folds, dysplastic ears, depressed nasal bridge, and cleft palate. Abnormalities of the thumbs and feet have been described, and also cardiovascular, renal and genital anomalies.

Hepatoblastoma in an infant with cat eye syndrome

Introduction: Cat eye syndrome (CES) is a rare chromosomal disorder with highly variable clinical presentations involving multiple organs. The features mimic other syndromes such as CHARGE or VACTERL, and genetic testing is required to confirm the diagnosis. CES and malignancy were not reported until recently in a 3-year-old child. Case report: We report a case of CES with hepatoblastoma presenting in infancy, highlighting the need to be vigilant during the follow-up of these patients. Conclusion: Our case report has possibly identified an association of malignancy with CES in infancy. Further studies linking the association of malignancy with CES may highlight the need for careful monitoring, a high index of suspicion and a low threshold for an ultrasound scan and AFP to ensure timely diagnosis and treatment.

Emanuel syndrome and congenital diaphragmatic hernia: A systematic review

BackgroundEmanuel Syndrome (ES), a rare chromosomal disorder caused by a supernumerary chromosome 22 derivative (der(22)t(11;22)), was identified in a fetus with congenital diaphragmatic hernia (CDH) at our fetal center. We aimed to identify a precedent for clinical care and patient outcomes to guide family decision-making. MethodsThis non-funded and non-registered study queried the entire CDH Registry (CDHR) including >10,000 patients since 1995 and conducted a systematic literature review for patients with concomitant ES and CDH. ResultsLiterature review captured 12 citations and identified 9 patients with CDH+ES from over 400 known ES cases. Given the rarity of the disease and to reduce bias, there were no exclusion criteria aside from non-English language. Of these 9, two underwent surgical CDH repair with neither surviving. The CDHR identified 6 patients with ES, all reported after 2013 and prenatally diagnosed. Median estimated gestational age was 39 weeks (range 37–40) and median birth weight was 2.72 kg (range 2.4–3.4 kg). 3 patients died within the first few postnatal days; surgical repair was not offered due to “anomalies” and “pulmonary hypertension” in two and one family chose comfort measures. The other 3 patients underwent surgical repair, and 2 were supported with ECMO. Two patients survived to discharge, incurring surgical comorbidities associated with severe CDH including gastrostomy dependence, tracheostomy, and CDH recurrence. ConclusionsES patients with CDH have potential to tolerate repair and survive to discharge, however with significant additional morbidity combined with severe challenges inherent to ES. This represents the largest series of patients with CDH and ES to date. Level of evidenceIV (Case series with no comparison group).

Diagnostic and therapeutic approach to children with Nijmegen breakage syndrome in relation to development of lymphoid malignancies.

Nijmegen breakage syndrome (NBS) is a rare chromosomal instability disorder. The majority of patients carry founder mutation in the NBN gene (c.657_661del5). Characteristic features of the NBS include progressive microcephaly, dysmorphic facial features, immunodeficiency, and high predisposition to malignancy with cumulative cancer incidence by the age of 20 years, and amounted to over 70%. The aim of study is to present the latest methods of diagnosis, potential cancer risk factors and treatment of lymphoid malignancies in children with NBS. To review the evidence using PubMed and Google Scholar search which included articles published between 2009-2021, focusing on articles published between 2013-2021. The average delay in diagnosis of NBS ranges from 4-5 years. Neonatal screening of T-cell excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) seems favourable in NBS. There are no specific protocols for the treatment of lymphoid malignancies in children with NBS, and full- dose chemotherapy is the most frequently applied method. Reducing the doses of chemotherapy does not significantly reduce the toxicity. Main cause of death is cancer progression and treatment-related mortality mostly associated with infectious complications. Patients with diagnosed cancer who received haematopoietic stem cell transplantation (HSCT) had significantly higher 20-year OS than those who did not (42.7% vs. 30.3%). Further meta-analysis is essential to establish the best monitoring and treatment regimen in patients with NBS and lymphoid malignancies.

A case report of Ring chromosome 18 with systemic Lupus Erythematosus and Crohn’s disease

Ring Chromosome 18 is a rare chromosomal disorder caused by missing pieces of one or both ends of chromosome 18. The clinical phenotype of the Ring 18 syndrome depended on the rate and the locality of genetic material lost. Here, we report a 27years old girl with symptoms including microcephaly, mental and motor retardation, hypotonia, and autoimmune diseases consist of Rheumatoid arthritis, Systemic Lupus Erythematosus, and Crohn's disease. This research contributes to a better understanding of disease and can lead to improvement in diagnosis and treatment. The Chromosomal analysis was performed based on the GTG banding technique on peripheral blood lymphocytes. Karyotype analysis indicated the existence of a Ring chromosome 18 with deletions at 18p11.32 and18q22-2. Following that, the parental karyotype of the affected girl confirmed that Ring 18 was caused by a de novo mistake very early in embryonic development. Ring chromosome 18 is a rare chromosomal disorder that is generally caused by de novo errors very early in the development of the embryo. Previously studies have reported a relationship between autoimmune diseases and Ring 18. Our patient has disclosed specific types of autoimmune diseases, including Systemic Lupus Erythematosus, and Crohn's disease.

15q26 deletion in a patient with congenital heart defect, growth restriction and intellectual disability: case report and literature review

Background15q26 deletion is a relatively rare chromosomal disorder, and it is described only in few cases. Patients with this aberration show many signs and symptoms, particularly pre- and postnatal growth restriction, developmental delay, microcephaly, intellectual disability and various congenital malformations.Case presentationWe report on a girl, 4 years old, of consanguineous parents, with a 15q26 deletion. Clinical manifestations included failure to thrive, developmental delay, microcephaly, dysmorphic facies with broad forehead, hypertelorism, narrowed eyelid slits and protruding columella. The patient also showed skeletal abnormalities, especially clinodactyly of the 5th finger, varus equine right foot and left club foot. Additionally, she had teething delay and divergent strabismus. Heart ultrasound displayed two atrial septal defects with left-to-right shunt, enlarging the right cavities. Routine cytogenetic analysis revealed a shortened 15q chromosome. Subsequent array analysis disclosed a terminal 9.15 Mb deletion at subband 15q26.1-q26.3. Four candidate genes associated with 15q26 deletion phenotype were within the deleted region, i.e. IGF1R, NR2F2, CHD2 and MEF2A.ConclusionWe report on an additional case of 15q26 monosomy, characterized by array-CGH. Molecular cytogenetic analysis allowed us to identify the exact size of the deletion, and four candidate genes for genotype-phenotype correlation. 15q26 monosomy should be considered when growth retardation is associated with hearing anomalies and congenital heart defect, especially atrioventricular septal defects (AVSDs) and/or aortic arch anomaly (AAA).

Cytogenomic characterization of a de novo 4q34.1 deletion in a girl with mild dysmorphic features and a coagulation disorder

Background4q deletion syndrome is a rare chromosomal disorder that mostly arises de novo. The syndrome is characterized by craniofacial dysmorphism, digital abnormalities, skeletal alterations, heart malformations, developmental delay, growth retardation, Pierre Robin sequence, autistic spectrum and attention deficit-hyperactivity disorder, although not every patient shows the same features. Array comparative genomic hybridization (aCGH) use improves the detection of tiny chromosomal deletions and allows for a better understanding of genotype–phenotype correlations in affected patients. We report the case of a 6-year-old female patient showing mild dysmorphic features, mild mental disabilities and a coagulation disorder as a consequence of a de novo del(4)(q34.1) characterized by aCGH.Case presentation A 6-year-old female patient exhibited special craniofacial features, such as backward-rotated ears, upslanted palpebral fissures, broad nasal bridges, anteverted nares, broad nasal alae, smooth philtrums, smooth nasolabial folds, thin lips, horizontal labial commissures, and retrognathia. In the oral cavity, maxillary deformation, a high arched palate, agenesis of both mandibular canines and fusion of two mandibular incisors were observed. She also displayed bilateral implantation of the proximal thumbs, widely spaced nipples, dorsal kyphosis, hyperlordosis, and clitoral hypertrophy. In addition, the patient presented with coagulopathy, psychomotor delay, attention deficit-hyperactivity disorder, and mild mental disability. A chromosomal study showed the karyotype 46,XX,del(4)(q34.1), while an aCGH analysis revealed an 18.9 Mb deletion of a chromosome 4q subtelomeric region spanning 93 known genes.ConclusionThe clinical manifestations of this patient were similar to those reported in other individuals with 4q deletion syndrome. Although most of the patients with a 4q34 terminal deletion share similarities, variations in phenotype are also common. In general, clinical effects of chromosomal deletion syndromes depend on the length of the deleted chromosomal segment and, consequently, on the number of lost genes; however, in all of these syndromes, there is no simple correlation between the phenotype and the chromosomal region involved, particularly in cases of 4q deletion.

A child with cat-eye syndrome and oculo-auriculo-vertebral spectrum phenotype: A discussion around molecular cytogenetic findings

Cat eye syndrome (CES) is a rare chromosomal disorder that may be evident at birth. A small supernumerary chromosome is present, frequently has 2 centromeres, is bisatellited, and represents an inv dup(22)(q11) in those affected. It's known that the 22q11 region is associated with disorders involving higher and lower gene dosages. Conditions such as CES, 22q11 microduplication syndrome (Dup22q11) and oculoauriculovertebral spectrum phenotype (OAVS) may share genes belonging to this same region, which is known to have a predisposition to chromosomal rearrangements. The conditions, besides being related to chromosome 22, also share similar phenotypes. Here we have added a molecular evaluation update and results found of the first patient described with CES and OAVS phenotype, trying to explain the potential mechanism involved in the occurrence of this association.

Report of a case with partial trisomy 9 mosaicism

Trisomy 9 syndrome and other related abnormalities such as full or mosaic trisomy 9 are very rare human chromosomal disorders. The disorders cause early pregnancy loss or death within 20 days after the birth which is accompanied by complex birth defects. The case reported here is a 26-year-old female, identified with partial trisomy of chromosome 9 by Array comparative genomic hybridization -aCGH, but has a longer life than reported in the medical literature and can give birth. The patient did not have abnormal mental or motor problems; no morphological ultrasound abnormalities; curved thumb and scattered warts on the left hand; gave birth to a healthy son after three consecutive stillbirths. The report has shown diverse clinical manifestations of trisomy 9 mosaic abnormalities in humans, contributing to a rare data source of trisomy 9 mosaic cases. Since then, improve knowledge of genetic counseling for rare cases of trisomy 9 mosaicism, especially in genetic counseling of prenatal diagnosis.

Acromegaly coexisting with turner syndrome

IntroductionAcromegaly is a clinical syndrome associated with overexpression of the growth hormone (GH). Turner syndrome (TS) is a rare chromosomal disorder resulting from partial or complete loss of X chromosome and is a common chromosome anomaly in humans. MethodsFor the patient due to the presence of short stature and primary ovarian insufficiency, karyotype analysis was performed. Results43-year-old acromegalic woman was that detected with a pituitary tumor during the assessment of her GH level and the exploration of the typical phenotype. The patient underwent transsphenoidal pituitary and the pathological result was reported as GH-secreting pituitary adenoma. A karyotype analysis was requested for the patient due to the presence of short stature and primary ovarian insufficiency and her karyotype was determined to be 45,X0/46,x,i(Xq)(q10). ConclusionBased on these signs and symptoms, coexistence of acromegaly and TS was diagnosed in our patient, which is an extremely rare occurrence that has been reported only in two patients. The evaluation of the clinical profile and karyotype pattern of our patient in line with the findings of recent studies indicated that the intact X chromosome could be inactivated in the cells of our patient that contained the 46,X,i(Xq) karyotype and that an extra copy of the GPR101 gene that is located in the Xq isochromosome could be expressed. This phenomenon may explain the emergence of this disease in middle ages, as seen in our patient who had a mosaic karyotype.

Generation of a human induced pluripotent stem cells (MUi015-A) from skin fibroblast of retinoblastoma patient with 13q deletion syndrome.

The 13q deletion syndrome is a rare chromosomal disorder caused by loss of the long arm of chromosome 13, and usually entails developmental delay, intellectual disability, behavioral problems and distinctive facial features. In this study, we successfully generated a human iPSC line (MUi015-A) from skin fibroblasts of a patient who had large deletion of chromosome 13, del(13)(q14q22). The MUi015-A line exhibited embryonic stem cell characteristics with consistent pluripotency marker expression and the capability of differentiating into three germ layers. The cell line provides a good tool in studying pathophysiology of the tumors, drug testing and gene therapy.

Prenatal diagnosis of a pure 15q distal trisomy derived from a maternal pericentric inversion: A case report

Distal trisomy or duplication of 15q is a very rare chromosomal disorder; most of the previously reported cases were derived from unbalanced translocations involving chromosome 15 and another chromosome, whereas other mechanisms (e.g. duplication) have rarely been reported. We herein report a very rare prenatal case of a partial 15q trisomy, a 42.64-Mb duplication of 15q22.2-q26.3, arising from a maternal pericentric inversion of chromosome 15 (p11q22) that was not the result of an unbalanced translocation or duplication, and was not associated with concomitant partial monosomy. Fetal ultrasound revealed isolated thickened nuchal translucency at 12 weeks and multiple abnormalities in the second trimester, including early growth restriction, unilateral ventriculomegaly, narrow cavum septi pellucidi with hypoplasia of the corpus callosum, unilateral postaxial polydactyly, clenched hands and clubfoot with clawing of the toes, and a particular general dysplastic and hypotrophic aspect of the heart. The distinctive aspects of the present case may help to refine the phenotype associated with distal duplication 15q. To the best of our knowledge, this is the first report of a prenatal diagnosis with a 15q22.2-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component.

Nadir bir olgu: Trizomi 8 Mozaisizm Sendromu

Trisomy 8 mosaicism syndrome (T8MS ) is a rare chromosome disorder caused by the presence of a extra chromosome 8 in some cells of the body. T8MS is a clinically variable condition associated with a number of developmental abnormalities. We report a of T8MS with dysmorphic features and congenital anomalies. A 3.5-month-old boy was referred to the genetic department because of his atypical facial appearance. Physical examination revealed microcephaly, hypertelorism, flattened nasal root, deeply located eyes, strabismus, dysplastic ears, cleft palate, deep hand and foot lines, camptodacty and hypotonicity. He had additional anomalies such as hearing loss, peripheral cataract in the left eye, bilateral advanced vesicoureteral reflux, and corpus callosum dysgenesis. Chromosome analysis revealed trisomy 8 mosaicism (47,XY,+8[11]/46,XY[39]). Mosacism was also confirmed by fluorescence in situ hybridization analysis.T8MS is clinically quite heterogeneous and frequently associated with dysmorphism, urogenital abnormalities, corpus callosum agenesis and camptodacty. Deep hand and foot lines are very characteristic for the T8MS. Our patient also had congenital anomalies related to T8MS previously reported in the literature. Correlation of genetic abnormalities with clinical phenotype is always important for the diagnosis of syndromes. In conclusion, chromosomal anomalies should be considered in the differential diagnosis in the dysmorphic patients accompanied by multiple congenital abnormalities and cytogenetic studies sholud be performed first.

Generation of iPSC line ICGi024-A from human skin fibroblasts of a patient with ring chromosome 18.

Ring chromosome 18 is a rare chromosomal disorders that usually originate de novo and correlate with clinical manifestation: developmental delay as well as microcephaly, brain and ocular malformations, hypotonia and skeletal abnormalities. We generate iPSC clonal cell line ICGi024-A with pluripotency properties which were demonstrated in vitro by three germ layer differentiation capacity. ICGi024-A can be used for disease modeling and fundamental investigation of ring chromosome instability.

The Changing Landscape of Genetics in the Philippines

In the beginning, medical genetics was concerned only with rare single gene or chromosomal disorders. However, the Human Genome Project has made available information of invaluable diagnostic and therapeutic importance. It links the genome with human health.
 It is becoming clear that all diseases or medical conditions have a genetic component with a huge proportion of the general population having a recognized genetic disorder. Presently, there is greater appreciation of genetic contributions to normal physiologic processes, early disease detection, pathogenesis, prevention and susceptibility to disease, disease prognostication and monitoring, the development of innovative diagnostic tests and novel therapeutic approaches. Genetics is currently the driving force in medical research.
 While the papers in this special 2017 Genetics issue of Acta Medica Philippina give different perspectives on genetics, certain key themes have become evident in the submissions. We highlight birth defects, molecular genetics, cancer genetics, dysmorphology–craniofacial syndromes, the importance of folic acid, metabolic disorders, and genetic counselling issues. With the expansion of our genetic understanding of normal physiologic processes and disease, the role of the genetic counselor has also undoubtedly increased. The challenge is to make these genetic advances benefit people/ patients and the public. There is a need to educate them and make them aware of the different facets of genetics and its implications to the patient, their families and disseminate these information to the community.
 The integration of genetics into medical practice will occur at a different pace for all areas in medicine. Genetic technology is available and accessible for everyone with interest to do genetic research in their corresponding medical field.
 It is realized though that the Philippines, being a developing country, needs to recognize the burden imposed by genetic disorders and birth defects. There must be political will and commitment to sup port the implementation of these genetic services. Knowledge about genetic disorders and birth defects must be enhanced and the goals of genetic services in terms of both individual/family welfare and public health must be delineated with ethical principles and cultural diversity respected.
 Catherine Lynn T. Silao, MD, PhD, FPPS Guest EditorInstitute of Human GeneticsNational Institutes of HealthUniversity of the Philippines Manila

A-251 3q29 Deletion Syndrome and Neuropsychological Functioning: Fraternal Twin Case Study

Abstract Objective The 3q29 Deletion Syndrome, first described in 2005, is a rare chromosomal disorder which results in a wide array of symptoms. Affected individuals present with complex neuropsychiatric profiles. The associated phenotype for this syndrome may include developmental delay, intellectual disabilities, attentional deficits, behavioral disturbances, and social and emotional issues. These individuals are at a higher risk of developing autism or schizophrenia. This case study describes the neuropsychological profiles of two fraternal twin girls, age 7, only one of whom was diagnosed with 3q29 Deletion Syndrome. Methods Both girls received comprehensive neuropsychoeducational evaluations to compare and contrast the following dimensions: Neurocognitive, Intellectual, Educational, Attentional, School Behavioral, Affective, and Personality Functioning. Results Twin 1, positive for 3q29 Deletion Syndrome, exhibits significant affective, behavioral, and cognitive difficulties secondary to her chromosomal disorder, which included learning disabled and oppositional presentations and emotional dyscontrol. Twin 2 exhibited superior intellectual and social functioning. Conclusions This study contributes to the understanding of the clinical presentation of 3q29 Deletion Syndrome by examining the relationship between fraternal twin sisters. Findings are consistent with earlier reports of the chromosomal disorder’s phenotype, yielding neurocognitive, emotional, and behavioral difficulties. Though the twins have widely different neuropsychological profiles, they have a close relationship. Twin 2, who models excellent prosocial behaviors, will be an asset to Twin 1 in all spheres. Ongoing efforts to improve Twin 1’s neuropsychological, social/emotional, and behavioral functioning will be facilitated via both psychological and psychopharmacological interventions.

A-046 The Need to Regulate Affect and Behavior Before Prescribing Stimulants

Abstract Objective The 3q29 Deletion Syndrome, first described in 2005, is a rare chromosomal disorder which results in a wide array of symptoms. Affected individuals present with complex neuropsychiatric profiles. The associated phenotype for this syndrome may include developmental delay, intellectual disabilities, attentional deficits, behavioral disturbances, and social and emotional issues. These individuals are at a higher risk of developing autism or schizophrenia. This case study describes the neuropsychological profiles of two fraternal twin girls, age 7, only one of whom was diagnosed with 3q29 Deletion Syndrome. Methods Both girls received comprehensive neuropsychoeducational evaluations to compare and contrast the following dimensions: Neurocognitive, Intellectual, Educational, Attentional, School Behavioral, Affective, and Personality Functioning. Results Twin 1, positive for 3q29 Deletion Syndrome, exhibits significant affective, behavioral, and cognitive difficulties secondary to her chromosomal disorder, which included learning disabled and oppositional presentations and emotional dyscontrol. Twin 2 exhibited superior intellectual and social functioning. Conclusions This study contributes to the understanding of the clinical presentation of 3q29 Deletion Syndrome by examining the relationship between fraternal twin sisters. Findings are consistent with earlier reports of the chromosomal disorder’s phenotype, yielding neurocognitive, emotional, and behavioral difficulties. Though the twins have widely different neuropsychological profiles, they have a close relationship. Twin 2, who models excellent prosocial behaviors, will be an asset to Twin 1 in all spheres. Ongoing efforts to improve Twin 1’s neuropsychological, social/emotional, and behavioral functioning will be facilitated via both psychological and psychopharmacological interventions.

Bifid cardiac apex in Pallister-Killian syndrome

Aim: Pallister-Killian syndrome (PKS) is a rare chromosomal disorder, caused by tissue-limited mosaicism for an isochromosome 12p. Prenatal diagnosis of PKS is generally incidental. Although clinical presentation of PKS varies, cytogenetic findings are constant, and include a tetrasomy of chromosome 12p. We report a case of prenatally diagnosed PKS with unique dysmorphic feature: bifid cardiac apex, a type of morphology that has not been documented before. Case presentation: Our patient was the 38-year-old pregnant woman who underwent amniocentesis. Cytogenetic analysis of amniotic fluid detected a mosaic karyotype with a supernumerary chromosome (SMC) in 64 % of fetal amniocytes. To determine the chromosomal origin of SMC, fluorescence in situ hybridization was performed and tetrasomy 12p was confirmed: mos 47,XY,+mar[18]/46,XY[10].ishi(12p)(8M16/SP6++,CEP12+,VIJyRM2196-). Ultrasound examination showed a fetus with cleft lip, echogenic focus in the left ventricle of the heart and shortened fetal long bones. After receiving a genetic counseling for PKS, the woman requested a termination of pregnancy. A postmortem inspection of the fetus revealed a complex heart anomaly that includes bifid cardiac apex and ventricular septal defect. Conclusions: This report expands the clinical manifestations of PKS with a unique feature of bifid cardiac apex, and highlights the targeted prenatal diagnosis of PKS if specific ultrasound markers are present.

P28 Marfan syndrome? Think again!

Abstract Background A 21 year old male was referred to the adult hypermobility clinic from the local rheumatologist with a suspected diagnosis of Marfan syndrome, based on his body habitus although he had presented to his GP with painful toes. Methods He had a background of autism,learning difficulties and was wearing glasses due to amblyopia. He had a history of dental crowding with two previous teeth extractions. There was no family history of note. On examination, his arm span was not greater than his height, there was no arachnodactyly, his palate was normal, but he had gum hypertrophy. His skin texture was normal, with no abnormal scarring or bruising, but there was presence of striae. His Beighton score was 4/9 and he had flat feet. There was reduced muscle mass and hypotonia, which was felt to be the cause of his hypermobility, rather than increased ligamentous laxity. There was evidence of gynaecomastia and lack of facial hair. The working diagnosis was Klinefelter syndrome due to his tall stature, gynaecomastia and absence of secondary male characteristics. Subsequently, the patient was referred to endocrinology and for genetic testing. Results The endocrinology team recognised the clinical features of male hypogonadism with small phallus (Tanner stage 2/3) and small testes, confirmed also by ultrasound. The patient reported absence of early morning erections. Blood tests confirmed hypergonadotropic hypogonadism (high luteinizing hormone, low testosterone) and the patient was commenced on testosterone therapy. His bone mineral density values lied within the expected range for age. Karyotype analysis confirmed the presence of 48,XXYY which is a chromosomal condition characterized by the presence of an extra X and Y chromosome in males. In terms of management, he attended our Outpatient Hypermobility Exercise Programme and was given advice on footwear. He was provided with extensive written information about this condition by the Rare Chromosome Disorder Support Group, Unique. Conclusion Our case report illustrates the importance of considering 48,XXYY syndrome in patients with typical body habitus and joint hypermobility. Marfanoid habitus is associated with connective tissue diseases, like hypermobile Ehlers-Danlos syndrome and Marfan syndrome, but also described in homocystinuria and Klinefelter syndrome. 48,XXYY was considered previously as a variant of Klinefelter syndrome, but now it is regarded as a separate syndrome with overlapping features with the Klinefelter syndrome. As in our case, the classical phenotypic characteristicsinclude gynaecomastia, small testes and tall stature. Most affected individuals are infertile. This syndrome is also associated with behavioural problems, learning difficulties, congenital heart defects, bone abnormalities, tremor, obesity, type 2 diabetes and/orrespiratory problems. Patients have an essentially normal life expectancy but require regular medical follow-up. Disclosures A. Madenidou None. V. Choida None. V. Reddy None. H. Kazkaz None.