Pitt-Hopkins Syndrome: Clinical and Molecular Findings of a 5-Year-Old Patient

Pitt Hopkins syndrome (PTHS) is a very rare condition and until now, approximately 500 patients were reported worldwide, of which not all are genetically confirmed. Usually, individuals with variants affecting exons 1 to 5 in the TCF4 gene associate mild intellectual disability (ID), between exons 5 to 8, moderate to severe ID and sometimes have some of the characteristics of PTHS, and variants starting from exon 9 to exon 20 associate a typical PTHS phenotype. In this report, we describe the clinical and molecular findings of a Caucasian boy diagnosed with PTHS. PTHS phenotype is described including craniofacial dysmorphism with brachycephaly, biparietal narrowing, wide nasal bridge, thin and linear lateral eyebrows, palpebral edema, full cheeks, short philtrum, wide mouth with prominent and everted lips, prominent Cupid’s bow, downturned corners of the mouth, microdontia and also the clinical management of the patient. The previously and the current diagnosis scores are described in this report and also the challenges and their benefits for an accurate and early diagnosis.

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Floating-Harbor syndrome: Presentation of the first Romanian patient with a SRCAP mutation and review of the literature

Balkan Journal of Medical Genetics ◽

10.2478/bjmg-2018-0005 ◽

2018 ◽

Vol 21 (1) ◽

pp. 83-86

Author(s):

M Budisteanu ◽

N Bögershausen ◽

SM Papuc ◽

S Moosa ◽

M Thoenes ◽

...

Keyword(s):

Intellectual Disability ◽

Short Stature ◽

Clinical Features ◽

Rare Condition ◽

Bone Age ◽

Speech Development ◽

Speech Delay ◽

Mild Intellectual Disability ◽

Intensive Program ◽

Floating Harbor Syndrome

Abstract Floating-Harbor syndrome (FHS) is a rare autosomal dominant syndrome characterized by short stature with delayed bone age, retarded speech development, intellectual disability and dysmorphic facial features. Recently, dominant mutations almost exclusively clustered in the final exon of the Snf2-related CREBBP activator protein (SRCAP) gene were identified to cause FHS. Here, we report a boy with short stature, speech delay, mild intellectual disability, dysmorphic features, and with genetically confirmed FHS. To the best of our knowledge, this is the first molecularly confirmed case with this syndrome reported in Romania. An intensive program of cognitive and speech stimulation, as well as yearly neurological, psychological, ophthalmological, otorhinolaryngological, pediatric and endocrinological monitoring for our patient were designed. We propose a checklist of clinical features suggestive of FHS, based on the main clinical features, in order to facilitate the diagnosis and clinical management of this rare condition.

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Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype

European Journal of Human Genetics ◽

10.1038/s41431-020-00769-7 ◽

2021 ◽

Author(s):

Meena Balasubramanian ◽

Alexander J. M. Dingemans ◽

Shadi Albaba ◽

Ruth Richardson ◽

Thabo M. Yates ◽

...

Keyword(s):

Intellectual Disability ◽

Protein Function ◽

Autism Spectrum ◽

Loss Of Function ◽

Mild Intellectual Disability ◽

Related Disorder ◽

Feeding Difficulties ◽

Facial Phenotype ◽

Novel Variants ◽

Common Behaviour

AbstractWitteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12.

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Searching for a dynamic equilibrium in decision making: the voices of adults with mild intellectual disability and their significant others in Hong Kong

Disability and Rehabilitation ◽

10.1080/09638288.2021.1925978 ◽

2021 ◽

pp. 1-11

Author(s):

Phyllis King Shui Wong

Keyword(s):

Decision Making ◽

Hong Kong ◽

Intellectual Disability ◽

Dynamic Equilibrium ◽

Significant Others ◽

Mild Intellectual Disability

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An orthodontic perspective on Larsen syndrome

BMC Oral Health ◽

10.1186/s12903-021-01454-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Madoka Yasunaga ◽

Hiroyuki Ishikawa ◽

Kenichi Yanagita ◽

Sachio Tamaoki

Keyword(s):

Foot Deformities ◽

Dental Arch ◽

Cephalometric Analysis ◽

Craniofacial Anomalies ◽

Nasal Bridge ◽

Skeletal Morphology ◽

Larsen Syndrome ◽

Craniofacial Dysmorphism ◽

Joint Dislocations ◽

Large Joint

Abstract Background Larsen syndrome (LS) is a rare disorder of osteochondrodysplasia. In addition to large-joint dislocations, craniofacial anomalies are typical characteristics. In this report, we performed orthodontic analyses, including skeletal and occlusal evaluations, to examine whether the craniofacial skeletal morphology leads to the craniofacial anomalies in LS. Case presentation A 5 year old Japanese girl who was clinically diagnosed with LS was referred to the orthodontic clinic in the Fukuoka Dental College Medical and Dental Hospital because of a malocclusion. Clinical findings at birth were knee-joint dislocations, equinovarus foot deformities, and cleft soft palate. The patient showed craniofacial anomalies with hypertelorism, prominent forehead, depressed nasal bridge, and flattened midface. To evaluate the craniofacial skeletal morphology, cephalometric analysis was performed. In the frontal cephalometric analysis, the larger widths between bilateral points of the orbitale were related to hypertelorism. The lateral cephalometric analysis revealed the midface hypoplasia and the retrognathic mandible. These findings were responsible for the flattened appearance of the patient’s face, even if the anteroposterior position of the nasion was normal. Her forehead looked prominent in relation to the face probably because of the retrognathic maxilla and mandible. Both the study model and the frontal cephalometric analysis indicated constriction of the upper and lower dental arches. The posterior crossbite facilitated by the premature contacts had developed in association with the constriction of the upper dental arch. Conclusions This patient had some craniofacial anomalies with characteristic appearances in LS. It was evident that the underlying skeletal morphology led to the craniofacial dysmorphism.

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Tubocutaneous Fistula

Case Reports in Obstetrics and Gynecology ◽

10.1155/2015/104360 ◽

2015 ◽

Vol 2015 ◽

pp. 1-2

Author(s):

Krishnaveni Nayini ◽

Clive Gie

Keyword(s):

Early Diagnosis ◽

Pelvic Inflammatory Disease ◽

Inflammatory Disease ◽

Fistulous Tract ◽

Rare Condition ◽

Diagnosis And Treatment ◽

Case Presentation ◽

Child Birth ◽

The Right

Introduction. Tubocutaneous fistula is a very rare condition; most cases described in the literature are secondary to endometriosis, tuberculosis, and complications of child birth and gynecological operations.Case Presentation. We report a case of 40-year-old woman who presented with tubocutaneous fistula secondary to pelvic inflammatory disease which was diagnosed in the setting of persistent discharging wound in the right groin.Conclusion. Tubocutaneous fistula is a rare condition. Salpingectomy and resection of fistulous tract is the treatment of choice as is treating the underlying cause. Early diagnosis and treatment of these patients are essential for avoiding long term complications.

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