The infant presented in the above clinical case had novel homozygous mutation in PYCR1 gene which is likely pathogenic variant of autosomal recessive cutis laxa type 2B/3B [3]. PYCR1 gene helps in synthesis of proline from glutamate. [link.springer.com]

Discussion The index patient presented with seizures and generalized hypotonia. [ncbi.nlm.nih.gov]

The index patient presented with seizures and generalized hypotonia. [idoj.in]

ARCL I patients have a striking presentation with systemic involvement and life-threatening organ symptoms. [nature.com]

We are reporting a case of congenital ARCLIIa, in a child who had primarily presented with right-sided pneumonia. [mansapublishers.com]

• Disability

  Additional manifestations may include seizures, intellectual disability, congenital hip dislocation, inguinal hernia, and cortical and cerebellar malformations. Pretibial pseudo-ecchymotic skin lesions have occasionally been associated. [findexpertmd.com]

  Affected individuals may experience growth delays, developmental delays, failure to thrive, intellectual disability, joint laxity and skeletal malformations. [rarediseases.org]

  Neurological Features The neurological findings common to ARCL2A and ARCL2B patients are intellectual disability, hypotonia, psychomotor retardation, microcephaly, and seizures. [mdpi.com]

  Age at ascertainment appeared as the unique phenotypic discriminator with earlier age more commonly associated with facial dysmorphism (p .02), high/cleft palate (p .005), intellectual disability/global developmental delay (p .013), and seizures (p .024 [onlinelibrary.wiley.com]

  MEF2C haploinsufficiency syndrome is an emerging neurodevelopmental disorder associated with intellectual disability, autistic features, epilepsy, and abnormal movements. [scinapse.io]

• Anemia

  A CELLULE FALCIFORMI (RDG010) ANEMIE EREDITARIE (RDG010) ANEMIE SIDEROBLASTICHE (RDG010) BLACKFAN-DIAMOND, ANEMIA DI (RDG010) FANCONI, ANEMIA DI (RDG010) FAVISMO (RDG010) METAEMOGLOBINEMIA DA DEFICIT DI METAEMOGLOBINAREDUTTASI (RDG010) SFEROCITOSI EREDITARIA [malattierare.toscana.it]

  Association of hemolytic anemia and early-onset pulmonary emphysema in three siblings. J Pediatr. 1984 Aug. 105(2):247-51. [QxMD MEDLINE Link]. Alehossein M, Pourgholami M, Kamrani K, Soltani M, Yazdi A, Salamati P. [emedicine.medscape.com]

  La talasemia mayor se asocia con esplenomegalia y anemia. [genaden.com]

  In a family with four infants born to the same consanguineous parents all children presented at birth with dysmorphic features, cutis laxa and hypertrichosis, hepatomegaly, splenomegaly, liver failure, hemolytic anemia, thrombocytopenia and genitourinary [nature.com]

• Low Set Ears

  ears, long philtrum, drooping facial skin). [findexpertmd.com]

  ears Low set ears Lowset ears [ more ] 0000369 Malar flattening Zygomatic flattening 0000272 Microcephaly Abnormally small skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ] 0000252 [rarediseases.info.nih.gov]

• Cutis Laxa

  SNOMED CT Concept 138875005 Clinical finding 404684003 Disease 64572001 Developmental disorder 5294002 Inherited cutis laxa 254220005 Cutis laxa, autosomal recessive 59451000 Cutis laxa, recessive, type II 254223007 Autosomal recessive cutis laxa type [findacode.com]

  Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica. [pubmed.ncbi.nlm.nih.gov]

  Synonym(s) ARCL2A; Autosomal recessive cutis laxa, type 2A; Cutis laxa, autosomal recessive, type 2A; OMIM 219200; Wrinkly skin syndrome Definition This section has been translated automatically. [altmeyers.org]

  Discriminative features in three autosomal recessive cutis laxa syndromes: cutis laxa IIA, cutis laxa IIB, and geroderma osteoplastica. Int J Mol Sci. 2017;18(3):635. [link.springer.com]

• Skin Lesion

  Keywords: ATP6V0A2-related cutis laxa; Ehlers-Danlos-like skin lesions; autosomal recessive cutis laxa; type 2A (ARCL2A). © 2014 Wiley Periodicals, Inc. [pubmed.ncbi.nlm.nih.gov]

  Pretibial pseudo-ecchymotic skin lesions have occasionally been associated. [findexpertmd.com]

  lesions very similar to those found in classical Ehlers–Danlos syndrome. [scinapse.io]

  Type 2 usually develops following acute inflammatory skin lesions, in which the areas affected by the skin lesions develop cutis laxa skin symptoms. [rarediseases.org]

• Small Head

  Wrinkly Skin Syndrome, which causes wrinkled skin, small head size, and mental retardation, as well as muscle and skeletal problems, is caused by mutations in the same ATP6V0A2 gene. [cutislaxa.org]

  […] skull Decreased circumference of cranium Decreased size of skull Reduced head circumference Small head circumference [ more ] 0000252 Midface retrusion Decreased size of midface Midface deficiency Underdevelopment of midface [ more ] 0011800 Motor delay [rarediseases.info.nih.gov]

• Muscle Hypotonia

  Developmental delay can be observed in the majority of the children, partially due to muscle hypotonia and to some degree hyperflexible joints. [nature.com]

• Hypertelorism

  […] variable severity, ranging from wrinkly skin to cutis laxa associated with pre- and post-natal growth retardation, hypotonia, mild to moderate developmental delay, late closure of anterior fontanelle, and craniofacial dysmorphism (including microcephaly, hypertelorism [findexpertmd.com]

  Affected infants may have distinctive facial features including eyes that are farther apart than normal (ocular hypertelorism), low-set, malformed (dysplastic) ears, highly arched palate, and a small, receding jaw (retrognathia). [rarediseases.org]

  Child had dysmorphism in the form of sagging cheeks, maxillary hypoplasia, prognathism, posteriorly placed large and low set ears, hypertelorism, down slanting palpebral fissures, wide open anterior fontanelle, medial epicanthal folds, depressed nose, [ncbi.nlm.nih.gov]

  [4] FBLN4 ( EFEMP2)-related cutis laxa (ARCL1B) is often characterized by accompanying severe cardiovascular symptoms include arterial stenosis, tortuosity, and aneurysms along with skeletal malformations, retrogenia, high-arched palate, and orbital hypertelorism [emedicine.medscape.com]

• Large Anterior Fontanels

  Generalized cutis laxa, brittle hair, microcephaly, large anterior fontanel (6 × 5 cm), midfacial hypoplasia, anteverted nares, down-slanting palpebral fissures, epicanthal folds, highly arched palate and strabismus were noted after birth. [nature.com]

• Prominent Nasal Root

  nasal root with funnel nose, small, low-set ears, long philtrum, drooping facial skin). [findexpertmd.com]

• Seizure

  Developmental epilepsies are age-dependent seizure disorders for which genetic causes have been increasingly identified. [scinapse.io]

  […] poor growth hair, abnormal (thin, brittle, fine) hypotonia joint hypermobilty, dislocations, laxity joint laxity lipodystrophia microcephaly (<2 SD for age) MRI, brain, abnormalities [-] myopia onset, infancy onset, neonatal psychomotor retardation seizures [metagene.de]

  Additional manifestations may include seizures, intellectual disability, congenital hip dislocation, inguinal hernia, and cortical and cerebellar malformations. Pretibial pseudo-ecchymotic skin lesions have occasionally been associated. [findexpertmd.com]

  Discussion The index patient presented with seizures and generalized hypotonia. [ncbi.nlm.nih.gov]

  The index patient presented with seizures and generalized hypotonia. [idoj.in]

• Ataxia

  Apraxia Ataxia-Oculomotor Apraxia 810,75€ Add to cart Friedreich ataxia Friedreich ataxia 598,00€ Add to cart Episodic ataxia type 1 Episodic ataxia type 1 1 023,50€ Add to cart Episodic ataxia type 2 Episodic ataxia type 2 631,35€ Add to cart Episodic [bioarray.es]

  Neurologic deterioration may include progressive cognitive decline, ataxia, neuropathy, and myopathy. [scinapse.io]

  Neurological regression can be associated with a variety of symptoms including slurred speech, an inability to coordinate voluntary movements (ataxia), and increased muscle tone and stiffness (spasticity). [rarediseases.org]

  ATM Ataxia - telangiectasia AR DESCRIPCIÓN Ataxia - telangiectasia: Anim pariatur cliche reprehenderit, enim eiusmod high life accusamus terry richardson ad squid. [genaden.com]

• Apraxia

  Ataxia-Oculomotor Apraxia 810,75€ Add to cart Friedreich ataxia Friedreich ataxia 598,00€ Add to cart Episodic ataxia type 1 Episodic ataxia type 1 1 023,50€ Add to cart Episodic ataxia type 2 Episodic ataxia type 2 631,35€ Add to cart Episodic ataxia [bioarray.es]

  APTX Ataxia con apraxia oculomotora e hipoalbuminemia de inicio temprano AR DESCRIPCIÓN Ataxia con apraxia oculomotora e hipoalbuminemia de inicio temprano: Anim pariatur cliche reprehenderit, enim eiusmod high life accusamus terry richardson ad squid [genaden.com]

We suggest a simple and practical diagnostic approach for the workup of patients with a suspected autosomal recessive cutis laxa (Figure 5). [nature.com]

/ 778068007 SNOMEDCT-ES (treatment) / 778068007 distrofia muscular de las cinturas de las extremidades tipo 2A autosómica recesiva Leyden-Möbius muscular dystrophy SNOMEDCT-ES (trastorno) / 715341003 SNOMEDCT-ES (treatment) / 715341003 www.wordscope.com [wordscope.com]

You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments. [rarediseases.info.nih.gov]

Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. [rarediseases.org]

The presence of the metabolic alteration has consequences both for organ involvement, prognosis assessment and counselling. [nature.com]

Prognosis The lifespan of some patients with cutis laxa (elastolysis) may not be significantly decreased. Patients with the autosomal dominant form have a normal life expectancy. [emedicine.medscape.com]

Next generation sequencing was performed in genetically unsolved patients with progeroid features, neurological and eye involvement to assess the underlying etiology. [scinapse.io]

In cutis laxa patients mutations have been demonstrated in elastin or fibulin genes, but in the majority of patients the underlying genetic etiology remains unknown. [nature.com]

Epidemiology Cutis laxa (elastolysis) is rare. Congenital forms of cutis laxa are more common than acquired disease. The recessively inherited form is most frequent and most severe. Autosomal dominant forms also exist. [emedicine.medscape.com]

Zurück zum Zitat Marsden CD, Hallett M, Fahn S (1983) The nosology and pathophysiology of myoclonus. In: Marsden CD, Fahn S (eds) Movement disorders. [springermedizin.de]

Am J Med Genet A 164A:1245–53 Article PubMed Google Scholar Marsden CD, Hallett M, Fahn S (1983) The nosology and pathophysiology of myoclonus. In: Marsden CD, Fahn S (eds) Movement disorders. [link.springer.com]

Pathophysiology Cutis laxa (elastolysis) is characterized by degenerative changes in the elastic fibers resulting in loose, pendulous skin. The skin is sagging, redundant, and stretchable, with reduced elastic recoil. [emedicine.medscape.com]

Pathophysiological aspects in ARCL type II patients with a ATP6V0A2 defect As described above, a large number of families with ARCL type II or WSS2, 22 with a distinct phenotype showed loss-of-function mutations in the a2-subunit of the V-type H+-ATPase [nature.com]

In ARCL1A, the mutations in both copies of this gene cause an altered structure of the protein product, preventing its transport out of the cells where it is produced and into the extracellular matrix. [cutislaxa.pitt.edu]

Variants in ATP6V0A2 impair Golgi vesicle trafficking and prevent the production of functional glycosylation. This results in reduced or abnormal elastic fiber formation. [preventiongenetics.com]

Management of individuals with cutis laxa includes treatment of symptoms, such as surgical repair of hernias, medications such as beta-blockers may be considered to prevent growth of aortic aneurysms, and pulmonary emphysema is treated symptomatically [cutislaxa.org]

In addition, some subtypes of cutis laxa have only been reported in a handful of individuals, which prevents physicians from developing a complete picture of associated symptoms and prognosis. [rarediseases.org]