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American Journal of  Medical 
Science and Innovation (AJMSI) 

It is Not a Curse! It is Neurofibromatosis 1 (NF1): A Case Report from Rural Kenya
Vonwicks C. Onyango1*, Nicholas M. Mutuma2, Samuel M. Gachie2; Boniface Mutiso2, Nicholas Auma3, William C. Fryda MD1

Volume 3 Issue 1, Year 2024
ISSN: 2836-8509 (Online)

DOI: https://doi.org/10.54536/ajmsi.v3i1.2709
https://journals.e-palli.com/home/index.php/ajmsi

Article Information ABSTRACT

Received: April 07, 2024
Accepted: May 12, 2024
Published: May 15, 2024

Neurofibromatosis 1 (NF1) is an autosomal dominant genetic disorder caused by mutations 
in the NF1 gene, with near complete penetrance and variable clinical presentation. Patients 
classically have café-au-lait macules, neurofibromas, skin freckles, and Lisch nodules, among 
other multisystemic features. Long-term management in a multidisciplinary team focuses 
on surveillance and treating complications. NF1 is a rare disease in Kenya, often leading to 
myths and misconceptions about its nature, especially among rural communities. We present 
a classical case from rural Kenya whose diagnosis was delayed by a belief  that it was the 
result of  a curse. We aim to highlight the importance of  making this diagnosis and its linkage 
to a long-term care plan within a primary health care setting.

Keywords
Neurofibromatosis 1, NF1, 
Von Recklinghausen Disease, 
Café-Au-Lait Macules, 
Neurofibromas, Skin Freckles, 
Kenya

1 Department of  Medicine, St. Joseph Rift Valley Hospital, Gilgil, Nakuru County, Kenya
2 Department of  Outpatient, St. Joseph Rift Valley Hospital, Gilgil, Nakuru County, Kenya
3 Department of  Endoscopy, St. Joseph Rift Valley Hospital, Gilgil, Nakuru County, Kenya
* Corresponding author’s e-mail: drvonczelo@gmail.com

INTRODUCTION
Neurofibromatosis type 1 (NF1) is a multisystem autosomal 
dominant genetic disorder that is commonly associated 
with skin, neurological, and skeletal manifestations (i.e., 
café au lait spots, neurofibromas, scoliosis, and long bone 
dysplasia, etc.). The pooled birth incidence is approximately 
1:2600 individuals, while the pooled prevalence is about 
1:3000 persons (Lee et al., 2023). The manifestations of  
NF1 are caused by a mutation in or a deletion of  the NF1 
gene located on chromosome 17q11.2 (Gutmann et al., 
2017). The gene product, neurofibromin, serves as a tumor 
suppressor gene, and its decreased production or absence 
leads to the various clinical manifestations of  NF1. The 
penetrance (i.e., the likelihood of  an individual carrying 
the gene variant manifesting clinical disease) of  the 
disease is almost 100%. The clinical features of  NF1 are 
protean, and typical findings include café-au-lait macules 
(hyperpigmented macules appearing in childhood and 
increasing in early adulthood, freckling (especially axillary 
and inguinal regions, called Crowe sign), Lisch nodules (tan-
colored hamartomas of  the iris virtually pathognomonic 
of  NF1), and tumors that may be benign or malignant 
(i.e., neurofibromas, gliomas, especially optic gliomas, and 
soft tissue sarcomas, e.g., rhabdomyosarcomas and glomus 
tumors). Neurofibromas are the most commonly seen 
benign peripheral nerve sheath tumors that are composed 
of  a mixture of  Schwann cells, fibroblasts, perineurial cells, 
and mast cells (Ortonne et al., 2018). They include discrete 
cutaneous neurofibromas (the most common type, usually 
soft, fleshy, sessile, or pedunculated) (Plotkin et al., 2012), 
plexiform neurofibromas (located superficially or deeply in 
the skin and associated with overgrowth of  skin and soft 
tissues with ensuing disfigurement of  patients) (Prada et 

al., 2012), and nodular fibromas. Patients may also have 
bone abnormalities, e.g., scoliosis, long bone dysplasia, 
pseudarthroses, and stunted growth. Neurological 
manifestations include neurocognitive deficits, learning 
disabilities, and seizures. Cardiovascular features include 
an increased incidence of  congenital heart disease 
and hypertension. NF1 may be associated with other 
endocrinological diseases, including pheochromocytoma 
and multiple endocrine neoplasia type 2B (MEN 2B). 
When clinically indicated, MRI of  the brain in NF1 shows 
focal areas of  increased signal intensities (appearing as 
bright spots) and increased brain volume (DiMario & 
Ramsby, 1998; Van Es et al., 1996).  The diagnostic criteria 
for NF1 developed by the United States National Institutes 
of  Health (NIH) Consensus Conference and updated in 
2021 are shown in Table 1(Legius et al., 2021). Consensus 
guidelines for the management of  NF1 patients among 
various clinical societies generally recommend care by a 
multidisciplinary team of  dedicated specialists throughout 
the patient’s lifetime. Emphasis is given to long-term 
surveillance for and treatment of  complications, as well as 
genetic counseling for patients and their families (Ferner 
et al., 2007; Stewart et al., 2018). Patients with NF1 have 
an increased lifetime risk for both benign and malignant 
tumors (Masocco et al., 2011). Affected children and adults 
may experience psychological problems with poor self-
image and anxiety (Sanagoo et al., 2019). The life expectancy 
is 8 years less than in the general population (Wilding et 
al., 2012). A new emerging technology, e.g., clustered 
regularly interspaced short palindromic repeats (CRISPR)-
aasociated protein 9 (CRISPR/Cas9) gene editing system, 
may soon be used for specific therapeutic targets in NF1 
(Moutal et al., 2017).



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Sphenoid wing dysplasia is not a separate criterion in case 
of  an ipsilateral orbital plexiform neurofibroma.

CASE SUMMARY
Clinical History and Physical Examination
A 21-year-old single man, a college student from Elburgon, 
Nakuru County, Kenya, presented to us with a history 
of  increasing numbers of  generalized soft nodular, non-
tender, and non-pruritic skin swellings and hyperpigmented 
macular lesions over the last 7 years. The swellings and 
macular-patchy lesions had been present at birth but 
had been dramatically increasing in size, number, and 
distribution since joining high school at age 14. They were 
now more evenly distributed over the torso, arms, legs, and 
neck. He was the firstborn among 5 siblings, the rest of  
whom were in good health. There was no known family 
history of  a similar illness. He was accompanied by his 
mother, who reported that he was born with a deformity of  
his upper back, which was slightly bent forward and to the 
right. He had an otherwise normal childhood with normal 
developmental milestones, no convulsions, no visual 
problems, and above-average school performance, leading 
to his current college enrollment where he was pursuing a 
diploma in electrical engineering. He was happily dating a 
girl at the same college. Their main reason for consulting 
us was to get a medical diagnosis rather than live with a 
suspicion of  a possible ‘cultural curse.’ Apparently, the 
family thought that he had been “cursed” and had sought 
numerous “spiritual solutions!”
On clinical examination, he was in good general health, and 
not in any obvious distress. He had normal vital signs, with 
a blood pressure of  105/63 mmHg and a pulse rate of  85 
bpm. His skin had generalized nodular swellings, especially 
over the arms, torso, thighs, and neck. These were of  
various sizes, ranging from 2 to 6cm, soft, non-tender, 
not attached to the skin, and movable easily in all planes. 
They were associated with generalized hyperpigmented 
macules, especially in the torso and axillary regions. He 

had bilateral axillary and inguinal freckles, which appeared 
much darker due to his dark skin color. He had an obvious 
thoracic scoliosis, while the rest of  the musculoskeletal 
exam was unremarkable. His neurological exam was 
unremarkable, with grossly normal visual acuity and visual 
fields by direct confrontation. He was recommended for a 
full ophthalmological slit lamp evaluation. He had normal 
heart sounds with no murmurs. The rest of  his physical 
exam was normal.

Diagnosis
In view of  the nodular swellings being consistent with 
neurofibromas (Figure 1), the macular hyperpigmented 
skin lesions being café-au-lait spots (Figure 2), the 

Table 1: Revised diagnostic criteria for neurofibromatosis type 1 (NF1) (Legius et al., 2021)
A: The diagnostic criteria for NF1 are met in an individual who does not have a parent diagnosed with NF1 if  2 or 
more of  the following are present
▪︎ 6 or more café-au-lait macules over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in 
greatest diameter in post pubertal individuals*
▪︎ Freckling in the axillary or inguinal region*
▪︎ 2 or more neurofibromas of  any type or 1 plexiform neurofibroma
▪︎ Optic pathway glioma
▪︎ 2 or more iris Lisch nodules identified by slit lamp examination or 2 or more choroidal abnormalities (CAs) – defined 
as bright, patchy nodules imaged by optical coherence tomography (OCT)/near-infrared reflectance (NIR) imaging
▪︎ A distinctive osseous lesion such as sphenoid dysplasia,  anterolateral bowing of  the tibia, or pseudarthrosis of  a long bone
▪︎ A heterozygous pathogenic neurofibromin 1 (NF1) variant with a variant allele fraction of  50% in apparently 
normal tissue such as white blood cells
B: A child of  a parent who meets the diagnostic criteria specified in A merits a diagnosis of  NF1 if  1 or more of  
the criteria in A are present

* If  only café-au-lait macules and freckling are present, the diagnosis is most likely NF1, but exceptionally the person might have another 
diagnosis such as Legius syndrome. At least 1 of  the 2 pigmentary findings (café-au-lait macules or freckling) should be bilateral.

Figure 1: Cutaneous neurofibromas seen here as 
numerous nodular lesions (blue arrows) distributed on 
the torso anteriorly and posteriorly as well as on both 
upper and lower arms. More neurofibromas were present 
on the head, neck, and both lower limbs.
Key: The patient had more than 60 cutaneous neurofibromas of  
variable sizes, which were soft, fleshy, and non-tender, with some 
being sessile and others pedunculated. These were distributed all 
over the skin, especially in the torso (both anteriorly and posteriorly).



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Figure 2: Café-au-lait macules seen here as multiple hyperpigmented macules of  various sizes distributed over the 
anterior and posterior torso (red arrows). They were also seen in the neck, arms, hands, legs and feet
Key: The patient had more than 30 café-au-lait macules diffusely distributed on the skin, particularly on the torso. These are flat, uniformly 
hyperpigmented macules varying in color from light brown to dark brown with smooth and irregular borders. They resemble coffee with 
milk, hence the name

Figure 3:  Freckles seen in the left and right axillae appearing as dark-brownish discoloration of  the skin (blue arrows).
Key: Freckles are discolorations of  the skin due to overproduction of  melanin and may range in color from red to dark brown. Due to 
his dark skin, the patient had dark brown freckles in both the axillary and inguinal areas, with other freckles seen on the torso as well.

Figure 4:  Thoracic scoliosis seen in a posterolateral and posterior view images as bending of  the upper thorax to 
the right side
Key: Scoliosis is the sideways curvature of  the spine. The patient has had thoracic scoliosis on the right side since his childhood. This was 
not causing him any clinical symptoms



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presence of  bilateral axillary and inguinal freckles 
(Figure 3), and scoliosis (Figure 4), a clinical diagnosis of  
neurofibromatosis type 1 (NF1) (previously called Von 
Recklinghausen’s disease) was made. This was in keeping 
with the diagnostic criteria for NF1. Presently, he had no 
clinical indication for any extensive laboratory and imaging 
studies. A baseline complete blood count, random blood 
sugar, and creatinine were all normal.

Management and Follow-Up
We educated them extensively on the genetic nature of  the 
disease, its clinical manifestations, and proposed evaluation 
and monitoring over the years. This specifically includes 
an annual clinical evaluation seeking the nature and extent 
of  the physical manifestations of  the disease, annual blood 
pressure monitoring to rule out hypertension, a formal 
slit lamp examination for Lisch nodules, and surveillance 
against other associated neuro-endocrinological diseases, 
e.g., multiple endocrine neoplasia (MEN) syndromes. If  
he desired a better cosmetic appearance in the future, or 
if  the neurofibromas ever became problematic (painful, 
disfiguring, interfering with normal function, etc.), he would 
be offered surgical intervention. Additionally, we informed 
him about the autosomal dominant mode of  inheritance of  
the disease with a near-100% penetrance. This means each 
of  his future children will have a 50% chance of  inheriting 
the NF1 gene with clinical manifestations of  NF1, albeit 
with variable severity of  the disease. We referred him 
for a formal slit lamp ophthalmological evaluation and 
dermatological review. We’ll follow him up annually in the 
medical clinic with a multidisciplinary team on a long-term 
basis, with appropriate surveillance and management of  
complications as necessary.

DISCUSSION
Our patient met the diagnostic criteria for NF1 as per 
the 2021 NIH Consensus Conference diagnostic criteria 
(Legius et al., 2021). Neither of  his parents have NF1. He 
had >30 café-au-lait macules, bilateral axillary and inguinal 
freckles (which appeared darker in his dark African 
skin), >60 cutaneous neurofibromas, and scoliosis. The 
differential diagnoses included Legius syndrome, which 
is caused by a mutation in the SPRED1 gene and may 
have multiple café-au-lait macules, axillary freckling, and 
macrocephaly but lacks neurofibromas and central nervous 
system tumors (Legius et al., 2021). Neurofibromatosis type 
2 (NF2) is caused by a mutation of  the NF2 gene located 
on chromosome 22 and is predominantly associated with 
benign schwannomas, bilateral acoustic neuromas, a lack 
of  cognitive impairment, and no Lisch nodules (Plotkin 
et al., 2022). For our patient, the café-au-lait macules 
and cutaneous neurofibromas began in childhood and 
increased in number and distribution in puberty, with 
no associated visual or neurocognitive disability to date. 
The thoracic scoliosis was asymptomatic. Presently, none 
of  the neurofibromas were giving him pain or cosmetic-
related concerns. The delayed medical diagnosis was due 
to a poor understanding of  the disease in the community, 

and its subsequent cultural characterization as a possible 
“curse.” It is not uncommon for rare diseases (including 
neglected tropical diseases) to be seen as a curse in 
tropical Africa in general and Kenya in particular. This is 
largely fueled by illiteracy and entrenched cultural norms 
and practices, among other factors (Ochola et al., 2021). 
Luckily for him, this matter has now been resolved with 
the correct medical diagnosis and a full discussion on the 
nature of  NF1 and its impact on him and his current and 
future family prospects. Due to practical logistical reasons, 
his long-term management will be primarily overseen by 
the hospital physician, who will rationalize any testing 
needed based on the clinical presentation and oversee 
consultations with a multidisciplinary team including 
dermatologists, neurologists, orthopedic surgeons, 
psychological counselors, etc., as may be necessary. This 
is consistent with the UK and US consensus management 
guidelines (Ferner et al., 2007; Stewart et al., 2018). Genetic 
testing is used in exceptional cases, especially in prenatal or 
preimplantation diagnosis (Vernimmen et al., 2023). These 
tests are prohibitively expensive, yet a positive NF1 mutation 
test does not predict the severity or complications of  the 
disorder (Tamura, 2021). Presently, he is asymptomatic, 
and none of  his parents or siblings have any features of  
the disease. Most likely, he had a sporadic mutation of  the 
NF1 gene. We have recommended that a dermatologist 
and ophthalmologist review him for an initial evaluation 
and the planning of  long-term follow-up. 

CONCLUSION
Primary care physicians should easily diagnose NF1 
based on the diagnostic criteria and do a thorough clinical 
evaluation to exclude complications and associated 
medical conditions. The diagnosis should be fully 
discussed with the patient and their family to expel any 
myths and misconceptions about the disease and explore 
the implications of  the autosomal dominant nature of  
inheritance with a near-complete penetrance. The patient 
should subsequently be enrolled in long-term care within 
a multidisciplinary team led by the primary care physician, 
with an emphasis on regular clinical evaluation and 
surveillance against any complications.

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