Since 2011, eight males with an X-linked recessive disorder (Ogden syndrome, MIM #300855) associated with the same missense variant p.(Ser37Pro) in the NAA10 gene have been described. After the ...advent of whole exome sequencing, many NAA10 variants have been reported as causative of syndromic or non-syndromic intellectual disability in both males and females. The NAA10 gene lies in the Xq28 region and encodes the catalytic subunit of the major N-terminal acetyltransferase complex NatA, which acetylates almost half the human proteome. Here, we present a young female carrying a de novo NAA10 NM_003491:c.247C > T, p.(Arg83Cys) variant. The 18-year-old girl has severely delayed motor and language development, autistic traits, postnatal growth failure, facial dysmorphisms, interventricular septal defect, neuroimaging anomalies and epilepsy. Our attempt is to expand and compare genotype–phenotype correlation in females with NAA10-related syndrome. A detailed clinical description could have relevant consequences for the clinical management of known and newly identified individuals.
Basel-Vanagaite-Smirin-Yosef syndrome (BVSYS) is an extremely rare autosomal recessive genetic disorder caused by variants in the
MED25
gene. It is characterized by severe developmental delay and ...variable craniofacial, neurological, ocular, and cardiac anomalies. Since 2015, through whole exome sequencing, 20 patients have been described with common clinical features and biallelic variants in
MED25
, leading to a better definition of the phenotype associated with BVSYS. We report two young sisters, born to consanguineous parents, presenting with intellectual disability, neurological findings, and dysmorphic features typical of BVSYS, and also with bilateral perisylvian polymicrogyria. The younger sister died at the age of 1 year without autoptic examination. Whole exome sequencing detected a homozygous frameshift variant in the
MED25
gene: NM_030973.3:c.1778_1779delAG, p.(Gln593Argfs). This report further delineates the most common clinical features of BVSYS and points to polymicrogyria as a distinctive neuroradiological feature of this syndrome.
One of the recently described syndromes emerging from the massive study of cohorts of undiagnosed patients with autism spectrum disorders (ASD) and syndromic intellectual disability (ID) is ...White-Sutton syndrome (WHSUS) (MIM #616364), caused by variants in the
gene (MIM *614787), located on the long arm of chromosome 1 (1q21.3). So far, more than 50 individuals have been reported worldwide, although phenotypic features and natural history have not been exhaustively characterized yet. The phenotypic spectrum of the WHSUS is broad and includes moderate to severe ID, microcephaly, variable cerebral malformations, short stature, brachydactyly, visual abnormalities, sensorineural hearing loss, hypotonia, sleep difficulties, autistic features, self-injurious behaviour, feeding difficulties, gastroesophageal reflux, and other less frequent features. Here, we report the case of a girl with microcephaly, brain malformations, developmental delay (DD), peripheral polyneuropathy, and adducted thumb-a remarkable clinical feature in the first years of life-and heterozygous for a previously unreported, de novo splicing variant in
. This report contributes to strengthen and expand the knowledge of the clinical spectrum of WHSUS, pointing out the importance of less frequent clinical signs as diagnostic handles in suspecting this condition.
Variations in genes encoding for the enzymes responsible for synthesizing the linker region of proteoglycans may result in recessive conditions known as "linkeropathies". The two phenotypes related ...to mutations in genes
and
(encoding for galactosyltransferase I and II respectively) are similar, characterized by short stature, hypotonia, joint hypermobility, skeletal features and a suggestive face with prominent forehead, thin soft tissue and prominent eyes. The most outstanding feature of these disorders is the combination of severe connective tissue involvement, often manifesting in newborns and infants, and skeletal dysplasia that becomes apparent during childhood. Here, we intend to more accurately define some of the clinical features of
and
-related conditions and underline the extreme hypermobility of distal joints and the soft, doughy skin on the hands and feet as features that may be useful as the first clues for a correct diagnosis.
Pitt-Hopkins syndrome is a rare genetic form of severe psychomotor delay, caused by mutations in transcription cell factor-4 gene and characterized by distinctive dysmorphic features and abnormal ...breathing pattern. The current report describes the polygraphic features of the syndrome’s typical breathing pattern in a patient both in wakefulness and in sleep. The control of these breathing alterations is important to prevent the neurological sequelae linked to chronic cerebral hypoxemia in early ages. No data are available on effective treatment options for breathing abnormalities of Pitt-Hopkins syndrome. The authors polygraphically documented a reduction of apneic and hypopneic phenomena, with a significant improvement in saturation values, after the introduction of sodium valproate.
Abstract Background Mutations in the gene PRRT2 have been identified in a variety of early-onset paroxysmal disorders. To date associations between PRRT2 mutations and benign myoclonus of early ...infancy have not been reported. Clinical report We describe a baby affected by PRRT2 mutation and benign infantile epilepsy, with an episode of focal status epilepticus. During follow-up he developed benign myoclonus of early infancy. Discussion We hypothesize a pathogenic role of PRRT2 mutation in inducing benign myoclonus of early infancy, similarly to that at the origin of other PRRT2-related paroxysmal movement disorders, such as paroxysmal kinesigenic dyskinesia. Conclusions Currently the function of PRRT2 is poorly understood, even if a marked pleiotropy and variable penetrance of its mutations are well known. Our case concurs in expanding the broad clinical spectrum of PRRT2-related disorders.
Myhre syndrome (OMIM 139210) is a rare developmental disorder inherited as an autosomal dominant trait and caused by a narrow spectrum of missense mutations in the
SMAD4
gene. The condition features ...characteristic face, short stature, skeletal anomalies, muscle pseudohypertrophy, restricted joint mobility, stiff and thick skin, and variable intellectual disability. While most of the clinical features manifest during childhood, the diagnosis may be challenging during the first years of life. We report on the evolution of the clinical features of Myhre syndrome during childhood in a subject with molecularly confirmed diagnosis. The clinical records of 48 affected patients were retrospectively analysed to identify any early clinical signs characterizing this disorder and to better delineate its natural history. We also note that pericarditis and laryngotracheal involvement represent important life-threatening complications of Myhre syndrome that justify the recommendation for cardiological and ENT follow-up for these patients.
Conclusion
: Short length/stature, short palpebral fissures, and brachydactyly with hyperconvex nails represent signs/features that might lead to the correct diagnosis in the first years of life and direct to the proper molecular analysis. We underline the clinical relevance of pericarditis and laryngotracheal stenosis as life-threatening complications of this disorder and the need for careful monitoring, in relation to their severity.
What is Known
:
•
The clinical and radiological signs of the disease in children older than 7–8 years
.
•
Pericarditis, sometimes occurring with constrictive pericardium requiring pericardiectomy, has been reported as a recurrent feature but has not been adequately stressed in previous literature.
What is New
:
•
Short length/stature, short palpebral fissures, brachydactyly with hyperconvex nails represent clinical signs that might lead to diagnosis in the first years of life
.
•
Review of the literature showed that pericarditis and laryngotracheal complications represent major recurrent issues in patients with Myhre syndrome
.
To date, 5 cases of 17p13.1 microduplications have been described in the literature. Intellectual disability was reported as the core feature, together with minor facial dysmorphisms and obesity, but ...a characteristic phenotype for 17p13.1 microduplication has not been delineated. Here, we describe a patient with a 1.56-Mb de novo duplication in 17p13.1, affected by mild intellectual disability, facial dysmorphisms, obesity, and diabetes. By comparing the different phenotypes of currently described cases, we delineated the main clinical features of 17p13.1 microduplication syndrome. All patients described to date had variable facial dysmorphisms; therefore, it was difficult to define a common facial gestalt. Furthermore, we stress endocrinological abnormalities as important features and the need to monitor these over time.
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