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]

Individuals with these conditions often present with cutis laxa, progeroid features, and hyperextensible joints. [mdpi.com]

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]

The specific symptoms present, severity and prognosis can vary greatly depending upon the specific type of cutis laxa and the presence and extent of associated symptoms. [rarediseases.org]

• Asymptomatic

  The infant was discharged on day 10 of life and was asymptomatic until discharge. At 3 wk of age, the infant was noted to have a tender swelling on the right thigh region. Skiagram showed fracture of the right femur bone with osteopenic changes. [link.springer.com]

• Poor Feeding

  Symptoms cutis laxa dysmorphism failure to thrive feeding difficulties, poor feeding growth retardation, poor growth hair, abnormal (thin, brittle, fine) hypotonia joint hypermobilty, dislocations, laxity joint laxity lipodystrophia microcephaly (<2 SD [metagene.de]

• Poor Growth

  Symptoms cutis laxa dysmorphism failure to thrive feeding difficulties, poor feeding growth retardation, poor growth hair, abnormal (thin, brittle, fine) hypotonia joint hypermobilty, dislocations, laxity joint laxity lipodystrophia microcephaly (<2 SD [metagene.de]

• Small Teeth

  Patients with the syndrome may have reduced skin elasticity, dental abnormalities (small teeth, delayed eruption, caries), and delayed closure of the fontanel (Hucthagowder et al. Hum Mol Genet 18:2149–2165, 2009; Morava et al. [preventiongenetics.com]

• Kinky Hair

  Progressive neurodegeneration and connective tissue disturbances, together with the peculiar “kinky” hair, are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of patients are males. [scinapse.io]

• Muscle Hypotonia

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

• Psychomotor Retardation

  […] for age) MRI, brain, abnormalities [-] myopia onset, infancy onset, neonatal psychomotor retardation seizures strabismus [metagene.de]

• Atonic Seizures

  In this study, targeted resequencing of 644 individuals with epileptic encephalopathies led to the identification of six SLC6A1 mutations in seven individuals, all of whom have epilepsy with myoclonic-atonic seizures (MAE). [scinapse.io]

• Myoclonus

  The progressive myoclonus epilepsies (PMEs) comprise a group of rare and heterogeneous disorders defined by the combination of action myoclonus, epileptic seizures, and progressive neurologic deterioration. [scinapse.io]

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

Legend How to query Individual ID ID_report Reference Remarks Gender Consanguinity Country Population Age at death VIP Data_av Treatment Disease Phenotype details Genes screened Variants in genes Variants Panel size Owner 00289442 3022 - - F no Italy [databases.lovd.nl]

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]

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]

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]

In the follow up, one should emphasize the importance of caloric intake, developmental assessment, physiotherapy and evaluation of possible osteoporosis to prevent frequent fractures in some of the ARCL II and GO patients. [nature.com]