CFC is a phenotypically variable disorder; not all affected individuals will present with every finding. Further, some findings may be evident at birth while others may present later. [invitae.com]

Ulnar deviation of fingers, elbow contractures and cubitus valgus were also present, but they were less prevalent than in CS. Hip and knees contractures and feet anomalies (mostly characterized by pes valgus and planus) were also present. [ojrd.biomedcentral.com]

The blue boxes indicate the number of carrier patients detected and the syndromes they presented, the most frequent are marked with an asterisk (*). [revespcardiol.org]

Heart Congenital heart defects are present in over 75% of patients, with the most common heart defects being pulmonic stenosis and atrial or ventricular septal defects. [rarediseases.org]

Comparisons are presented as standardised incidence ratios (SIRs) with an exact 95% confidence interval (CI). [nature.com]

• Short Stature

  stature and suggestive facies PTPN11-p.Tyr63Cys Noonan 13 11 Child b Hidrops faetalis (neonatal death) PTPN-p.Tyr63Cys Noonan 14 12 Mother Short stature and pterigium coli (suspected Turner) PTPN-p.Asn308Asp Noonan 15 13 Father Cryptorchidism PTPN-p.Pro491Thr [revespcardiol.org]

  stature and skin abnormalities. [rarediseases.org]

  Additional features of this disorder in children and adults can include an unusually large head (macrocephaly), short stature, problems with vision, and seizures. [medlineplus.gov]

  Other anomalies are also frequently observed, such as short stature, pectus deformity, kyphosis/scoliosis, and ocular abnormalities (strabismus, nystagmus, myopia,hyperopia, and astigmatism). [invitae.com]

• Disability

  Data on functional and disability status published by Johnson et al. detected lower scores in CS compared to CFCS [15]. [ojrd.biomedcentral.com]

  Intellectual Disability There is some form of cognitive or neurologic delay in nearly all patients with CFC syndrome. Most individuals fall in the range of moderate intellectual disability. [rarediseases.org]

  People with this condition also have delayed development and intellectual disability, usually ranging from moderate to severe. Heart defects occur in most people with cardiofaciocutaneous syndrome. [medlineplus.gov]

• Developmental Delay

  hypotonia, motor delay), and developmental delay; however, the RASopathies have several overlapping phenotypic features due to their common underlying Ras/MAPK pathway dysregulation. [invitae.com]

  Later, cognitive developmental delay and other clinical manifestations may be observed. [rarediseases.org]

• Atrial Septal Defect

  In some individuals with congenital heart defects such as pulmonary stenosis and/or atrial septal defects, treatment with certain medications, surgical intervention, and/or other techniques may be necessary. [rarediseases.org]

  The heart problems most commonly associated with this condition include malformations of one of the heart valves that impairs blood flow from the heart to the lungs (pulmonic stenosis), a hole between the two upper chambers of the heart (atrial septal [medlineplus.gov]

• Pulmonary Valve Stenosis

  valve stenosis or hypertrophic cardiomyopathy, and patients with LEOPARD syndrome. [revespcardiol.org]

• Failure to Thrive

  Failure to thrive during infancy is typical, as are gastrointestinal complications such as reflux, vomiting, oral aversion, and constipation. [invitae.com]

  […] to thrive) Most children with CFC syndrome have a heart problem at birth. [kidshealth.org]

  Signs & Symptoms Most individuals are initially referred because of feeding difficulties (poor suck) and failure to thrive. Later, cognitive developmental delay and other clinical manifestations may be observed. [rarediseases.org]

  Infants with cardiofaciocutaneous syndrome typically have weak muscle tone (hypotonia), feeding difficulties, and a failure to grow and gain weight at the normal rate (failure to thrive). [medlineplus.gov]

• High Arched Palate

  Classic facial dysmorphology comprises macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of the supraorbital ridges, downslanting palpebral fissures, ptosis, short nose with depressed nasal bridge and anteverted nares, high-arched palate, [invitae.com]

• Heart Disease

  Genotype and Heart Disease. [revespcardiol.org]

  disease that enlarges and weakens the heart muscle (hypertrophic cardiomyopathy). [medlineplus.gov]

  Patients’ past medical history was reviewed in order to check for: (1) congenital orthopedic malformations; (2) achievement of neuro-motor developmental milestones; (3) use of orthosis; (4) physical activity; (5) congenital heart disease (CHD). [ojrd.biomedcentral.com]

• Sparse or Absent Eyelashes

  People with cardiofaciocutaneous syndrome also tend to have thin, dry, curly hair and sparse or absent eyelashes and eyebrows. [medlineplus.gov]

• Low-Set Posteriorly Rotated Ears

  posteriorly rotated ears. [invitae.com]

• Muscle Hypotonia

  (hypotonia) trouble feeding As children with CFC syndrome grow, they usually have: many moles on their skin many small bumps in the skin (keratosis pilaris) wrinkles on the palms and the soles of the feet trouble learning, thinking, and speaking thin [kidshealth.org]

  Skeletal muscle hypotonia of varying degree is a universal finding in CS and CFCS, and some authors speculated that this could be related to myopathy [23]. [ojrd.biomedcentral.com]

• Floppy Muscle

  If a prenatal ultrasound didn't find the condition before birth, doctors usually notice signs when the baby is born or soon after, such as: trouble breathing floppy muscles The doctor will: ask about the family history of genetic conditions do an exam [kidshealth.org]

• Coxa Valga

  Coxa valga subluxans (CVS) was radiologically diagnosed when femoral neck-shaft angle was > 140°. [ojrd.biomedcentral.com]

• Short Nose

  nose At birth, most babies with CFC syndrome also have: floppy, relaxed muscles (hypotonia) trouble feeding As children with CFC syndrome grow, they usually have: many moles on their skin many small bumps in the skin (keratosis pilaris) wrinkles on the [kidshealth.org]

  These include a high forehead that narrows at the temples, a short nose, widely spaced eyes (ocular hypertelorism), outside corners of the eyes that point downward (down-slanting palpebral fissures), droopy eyelids (ptosis), a small chin, and low-set [medlineplus.gov]

  Classic facial dysmorphology comprises macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of the supraorbital ridges, downslanting palpebral fissures, ptosis, short nose with depressed nasal bridge and anteverted nares, high-arched palate, [invitae.com]

• Hypertelorism

  There is also an underdevelopment (hypoplasia) of the ridges of the bone above the eyes (supraorbital ridges); widely spaced eyes (ocular hypertelorism); downslant of eyelid openings and drooping of one or both upperlids (ptosis). [rarediseases.org]

  These include a high forehead that narrows at the temples, a short nose, widely spaced eyes (ocular hypertelorism), outside corners of the eyes that point downward (down-slanting palpebral fissures), droopy eyelids (ptosis), a small chin, and low-set [medlineplus.gov]

  Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease.. Am J Dis Child., 116 (1968), pp. 373-380 [2] Dimpna CA, Cerro MJ, Carrasco JI, Portela F.. [revespcardiol.org]

• Depressed Nasal Bridge

  Classic facial dysmorphology comprises macrocephaly, broad forehead, bitemporal narrowing, hypoplasia of the supraorbital ridges, downslanting palpebral fissures, ptosis, short nose with depressed nasal bridge and anteverted nares, high-arched palate, [invitae.com]

Standard Therapies Treatment The treatment of CFC syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]

When necessary, surgical treatment should be performed as early as possible to allow minimally invasive or low impact surgical techniques. [ojrd.biomedcentral.com]

Lupo Journal of Clinical Medicine (2021) Hypertrophic Cardiomyopathy in Children: Pathophysiology, Diagnosis, and Treatment of Non-sarcomeric Causes Emanuele Monda, Marta Rubino, Michele Lioncino, Francesco Di Fraia, Roberta Pacileo, Federica Verrillo [nature.com]

As Rodriguez-Marín observed,34 this more effective classification, supported by genomic assessment, can facilitate more targeted treatments. [revespcardiol.org]

In standard prospective epidemiologic studies, the analysis often excludes study end points that occur before disease diagnosis. [nature.com]

Lupo Journal of Clinical Medicine (2021) Hypertrophic Cardiomyopathy in Children: Pathophysiology, Diagnosis, and Treatment of Non-sarcomeric Causes Emanuele Monda, Marta Rubino, Michele Lioncino, Francesco Di Fraia, Roberta Pacileo, Federica Verrillo [nature.com]

In addition, in some cases, treatment with anticonvulsant drugs may help prevent, reduce, or control seizures. [rarediseases.org]

However, important methodological differences in study design prevent a direct comparison of these two studies. [nature.com]